Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes.

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing.

Chronic immunoglobulin maintenance therapy in myasthenia gravis.

BACKGROUND AND PURPOSE: Long-term treatment of myasthenia gravis (MG) includes symptomatic and course-modifying therapies that target the immune system. Recently, both intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) have emerged as viable options for chronic therapy, considering the favourable safety-efficacy profile and possible immunosuppressant sparing properties. The aim was to investigate the outcomes of the long-term care of generalized MG with immunoglobulin (Ig). METHODS: This is a retrospective, repeated-measures design study. Charts of generalized MG patients, treated with IVIG/SCIG for at least 6 months, from January 2015 to January 2020, were analysed. The primary outcome was the mean change in Myasthenia Gravis Impairment Index (MGII) after treatment with Ig, comparing baseline to IVIG and SCIG treatment periods. Secondary outcomes included the changes in pyridostigmine, immunosuppressive medications and patient-reported outcome 'percentage of normal' (0%-100%). RESULTS: Thirty-four patients were treated with chronic Ig therapy (30 IVIG/SCIG, three SCIG, one IVIG). The mean durations of IVIG and SCIG periods were 21.8 ± 19.4 (range 3-64) months and 19.5 ± 11.3 (range 5-45) months respectively. There was a significant reduction in MGII scores (27.7 ± 15.7 baseline; 22.0 ± 17.4 IVIG period; 19.5 ± 18.1 SCIG period; F = 17.9; d.f. = 1.7; P < 0.01), pyridostigmine and immunosuppressant use (P = 0.00). The outcome 'percentage of normal' had a significant positive association with both treatments (P = 0.00). CONCLUSION: Our study results suggest that patients can be successfully transitioned to IVIG and from IVIG to SCIG in the chronic treatment of generalized MG with reductions in impairments and use of other medications and improvement in overall status with Ig therapy. Prospective, randomized studies are needed to clarify costs and comparative effectiveness.

Comparison of the single simple question and the patient acceptable symptom state in myasthenia gravis.

BACKGROUND AND PURPOSE: The single simple question (SSQ) is a simple and validated question asking what percentage of normal a patient feels with respect to their myasthenia gravis (MG), with 100% being normal. Patient acceptable symptom states (PASS) are based on a dichotomous 'Yes' or 'No' response, asking whether a patient is satisfied overall with their current status and thus measures holistic satisfaction with their MG state. Both are patient-reported self-assessments but assess different dimensions of MG. The objective was to determine thresholds for the SSQ when patients with MG achieve an acceptable PASS status. METHODS: A retrospective chart review was performed of consecutive MG patients attending a neuromuscular clinic, and SSQ and PASS responses, demographic, clinical and serological characteristics and disease severity by the MG impairment index were extracted. RESULTS: One hundred and fifty-seven consecutive patients were identified: 43 (27.4%) patients responded 'No' to the PASS question. Between the PASS 'Yes'/'No' groups, only SSQ (87.5 ± 13.4 vs. 52.3 ± 23.3; P < 0.001) and MG impairment index scores (9.2 ± 10.3 vs. 29.6 ± 16; P < 0.001) were significantly different. The receiver operating characteristic curve for PASS and SSQ had an area under the curve of 0.92 ± 0.024 (confidence interval 0.872-0.965, P < 0.001). An SSQ score ≥72.5% had 84.2% sensitivity and 86% specificity to classify patients as PASS positive. CONCLUSION: The PASS and SSQ patient-reported outcomes are closely associated and a SSQ threshold ≥72.5% predicts an acceptable MG state. Other demographic and disease-related factors did not influence the PASS response in this study.

Chronic stress, depression and personality type in patients with myasthenia gravis.

BACKGROUND AND PURPOSE: Stress is a known risk factor for the onset and modulation of disease activity in autoimmune disorders. The aim of this cross-sectional study was to determine any associations between myasthenia gravis (MG) severity and chronic stress, depression and personality type. METHODS: In all, 179 consecutive adult patients with confirmed MG attending the Neuromuscular Clinic between March 2017 and December 2017 were included. At baseline, patients were assessed clinically and they completed self-administered scales for disease severity, perceived stress, depression and personality type. RESULTS: Higher disease severity [Myasthenia Gravis Impairment Index (MGII)] showed a moderate correlation with depression score (Beck's Depression Inventory, Second Edition, r = 0.52, P < 0.001) and a lower correlation with chronic stress (Trier Inventory for Assessment of Chronic Stress, r = 0.28, P = 0.001). Chronic stress scores were different according to personality types (anova, P = 0.02). The linear regression model with MGII score as the dependent variable showed R2 = 0.34, likelihood ratio chi-squared 74.55, with P < 0.0001. The only variables that predicted disease severity were depression scores (P < 0.0001) and female sex (P = 0.003). CONCLUSIONS: A significant association of MG severity with depression and chronic stress was found, as well as with female gender. These findings should raise awareness that the long-term management of MG should address depression and potential stress and consider behavioural management to prevent stress-related immune imbalance.

Serious infections in patients with myasthenia gravis: population-based cohort study.

BACKGROUND AND PURPOSE: To characterize the frequency and risk of serious infections in patients with myasthenia gravis (MG) relative to age/sex/area-matched comparators. METHODS: This was a population-based cohort study in Ontario, Canada of patients with newly-diagnosed MG and 1:4 age/sex/area-matched general population comparators accrued from 1 April 2002 to 31 December 2015. The main outcome was a serious infection, defined by a primary diagnosis code on a hospitalization or emergency department record. We computed crude overall and sex-specific rates of infection among patients with MG and comparators, and the frequency of specific types of infection. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox regression. RESULTS: Among 3823 patients with MG, 1275 (33.4%) experienced a serious infection compared with 2973/15 292 (19.4%) of comparators over a mean follow-up of over 5 years. Crude infection rates among patients with MG were twice those in comparators (72.5 vs. 35.0 per 1000 person-years, respectively). The most common infection types were respiratory infections, particularly bacterial pneumonia. After adjustment for potential confounders, MG was associated with a 39% increased infection risk (adjusted hazard ratio, 1.39; 95% confidence intervals, 1.28-1.51). CONCLUSIONS: Patients with MG are at a significantly higher absolute and relative risk of serious infections compared with age/sex/area-matched comparators. This needs to be considered when selecting MG treatments and when planning vaccination/prophylaxis. Determining whether this risk is due to the use of immunosuppressive medications (vs. MG itself) is an important area for future research.

EQ-5D-5L and SF-6D health utility index scores in patients with myasthenia gravis.

BACKGROUND AND PURPOSE: Health utilities are a preference-based method of valuing health states that are used in healthcare research, such as economic evaluations. There are limited health utility valuation data for patients with myasthenia gravis (MG). The aim of the study was to describe health utilities for patients with MG and different health states, using the EQ-5D-5L and SF-6D utility instruments, and to explore clinical and demographic determinants of utilities in this population. METHODS: Patients completed the EQ-5D-5L and SF-6D. In addition, patients were assessed with the Myasthenia Gravis Foundation of America classification, Myasthenia Gravis Impairment Index and MG-QOL15 as disease-specific measures, and the Neuro-QoL Fatigue scale. We calculated mean utilities for each Myasthenia Gravis Foundation of America severity class. We built regression models for the EQ-5D-5L and SF-6D to determine the clinical and demographic factors that determine patients' valuation of their health state. RESULTS: Among 254 patients, mean EQ-5D-5L health utilities were as follows: Remission, 0.94 ± 0.03; Minimal Manifestations, 0.92 ± 0.04; Class I, 0.89 ± 0.06; Class II, 0.78 ± 0.16; Class III, 0.58 ± 0.24 and Class IV, 0.61 ± 0.22. Mean SF-6D health utilities were as follows: Remission, 0.83 ± 0.07; Minimal Manifestations, 0.86 ± 0.14; Class I, 0.82 ± 0.14; Class II, 0.67 ± 0.12; Class III, 0.56 ± 0.11 and Class IV, 0.50 ± 0.10. The limb/axial scores were more highly correlated to health utilities than ocular or bulbar scores. CONCLUSIONS: We present estimates of health utilities for patients with MG that can be used in cost-utility and decision analyses. Limb/axial symptoms had a higher impact on health utilities than ocular or bulbar symptoms, which might reflect the impact of mobility on health valuation.

Toronto Clinical Neuropathy Score is valid for a wide spectrum of polyneuropathies.

BACKGROUND AND PURPOSE: The Toronto Clinical Neuropathy Score (TCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy. In this study, we aimed to explore the performance of the TCNS in non-diabetic polyneuropathies. METHODS: We performed a prospective study from November 2016 to May 2017 of patients with non-diabetic polyneuropathy. Patients had clinical, electrophysiological and functional assessments of their polyneuropathy, and the findings were correlated with the TCNS. RESULTS: The TCNS correlated with all clinical, electrophysiological and disability measures of polyneuropathy, mostly at a moderate level (e.g. r = -0.58 for sural nerve action potential amplitude). Higher TCNS severity grades were associated with worse polyneuropathy on all measures in the lower limbs, and with worse electrophysiological parameters and vibration perception thresholds in the upper limbs. The scale also showed excellent reliability and accuracy (kappa, 0.92-0.93 for inter- and intra-observer reliability; area under the receiver operating characteristics curve, 0.93). CONCLUSION: The TCNS is a valid and reliable scale for a wide spectrum of polyneuropathies, and might be useful in clinical practise and research for the diagnosis and staging of polyneuropathy.

The road less travelled: Australian women's experiences with vulval cancer.

Despite advances in surgical treatments and the availability of more conservative treatment options, women treated for vulval cancer still experience significant complications such as urinary incontinence, lymphoedema, pruritus, sexual and intimacy issues. These issues can profoundly impact a woman's quality of life. The subjective experience of women diagnosed and treated for vulval cancer in the literature is limited, possibly due to its comparable rarity to other gynaecological and female cancers and because it was traditionally seen mainly in the elderly female population. Nonetheless, younger women are also being diagnosed with vulval cancer. This paper reports the findings from a qualitative study about twelve women's experiences with vulval cancer from diagnosis, through treatment and recovery. Women's feelings of isolation, their unmet information and support needs, physical concerns arising from vulval cancer, particularly after surgery, and the consequences for their body image and intimate relationships with partners, were highlighted within the data. The central findings from this study emphasise the need for further research to develop appropriate interventions for women with vulval cancer. It also highlights opportunities to improve clinical practice into the supportive care of women with this isolating disease.

Monogenic and chromosomal causes of isolated speech and language impairment.

The importance of a precise molecular diagnosis for children with intellectual disability, autism spectrum disorder and epilepsy has become widely accepted and genetic testing is an integral part of the diagnostic evaluation of these children. In contrast, children with an isolated speech or language disorder are not often genetically evaluated, despite recent evidence supporting a role for genetic factors in the aetiology of these disorders. Several chromosomal copy number variants and single gene disorders associated with abnormalities of speech and language have been identified. Individuals without a precise genetic diagnosis will not receive optimal management including interventions such as early testosterone replacement in Klinefelter syndrome, otorhinolaryngological and audiometric evaluation in 22q11.2 deletion syndrome, cardiovascular surveillance in 7q11.23 duplications and early dietary management to prevent obesity in proximal 16p11.2 deletions. This review summarises the clinical features, aetiology and management options of known chromosomal and single gene disorders that are associated with speech and language pathology in the setting of normal or only mildly impaired cognitive function.

Patients' satisfaction with fast-track surgery in gynaecological oncology.

This study investigates the experience and satisfaction with care of fast-tracked gynaecological patients. The Sydney Gynaecological Oncology Group, New South Wales, Australia, has previously shown the benefits of a fast-track surgery programme for gynaecology patients with both complex benign gynaecological pathology and gynaecological malignancy. The question of whether these benefits translate into a positive experience for fast-tracked patients, in the context of their hospital stay and healthcare team care, has not been previously explored in detail. A self-administered satisfaction questionnaire incorporating the European Organisation for Research and Treatment of Cancer (EORTC) cancer in-patient satisfaction with care measure (INPATSAT-32) questionnaire with additional questions was administered to 106 gynaecology participants at Royal Prince Alfred Hospital. Participants reported high levels of satisfaction with patient care and support received from doctors, ward nurses and the hospital as a service and care organisation, within the context of a fast-track surgical programme. Early hospital discharge after gynaecological surgery results in both enhanced recovery after surgery (ERAS) and high levels of patient satisfaction.

Exercise interventions for weight management during pregnancy and up to 1 year postpartum among normal weight, overweight and obese women: a systematic review and meta-analysis.

BACKGROUND: The prevalence of excessive gestation weight gain, extended postpartum weight retention and pregravid obese women is increasing and is associated with numerous adverse health outcomes. OBJECTIVE: To review the evidence from studies employing exercise-only interventions for weight management among pregnant and postpartum women. SEARCH STRATEGY: Ten databases were searched for randomised controlled trials conducted during pregnancy or within the 12 months following childbirth and published between 1990 and 2013. SELECTION CRITERIA: There were no restrictions to the type, frequency, duration or intensity of exercise intervention. Interventions not specifically designed to target weight were excluded. The outcomes were a change in body weight (kg) or body mass index (BMI; kg/m(2)). DATA COLLECTION AND ANALYSIS: All data were continuous and were reported as weighted mean differences (WMD), with 95% CIs. Data were analysed with a fixed-effect model and heterogeneity was determined using the I(2) statistic. RESULTS: Five studies were included in this review. Exercise significantly reduced gestational weight gain (WMD=-2.22 kg, CI -3.14 to -1.3, p≤0.00001) and had no significant effect on postpartum weight loss (WMD=-1.74 kg, CI -3.59 to 0.10, p=0.06) or BMI during pregnancy (WMD=-2.8 kg/m(2), CI -5.60 to 0.00, p=0.05) or postpartum (WMD=-0.54 kg/m(2), CI -1.17 to 0.08, p=0.09). CONCLUSIONS: There is currently limited evidence to suggest that exercise can be used to limit maternal gestational weight gain.

Patients' perspectives of fast-track surgery and the role of the fast-track clinical nurse consultant in gynecological oncology.

This study examines the role of the fast-track nurse in gynecology from a patient perspective. The fast-track nurse is a specialist nursing role, which coordinates patient care, in addition to providing specialized clinical care. Semistructured interviews were conducted with women who had fast-track surgery for gynecological cancer.

Transfer parameters for ICRP reference animals and plants collected from a forest ecosystem.

The International Commission on Radiological Protection (ICRP) have suggested the identification of a series of terrestrial, marine and freshwater sites from which samples of each Reference animal and plant (RAP) could be systematically collected and analysed. We describe the first such study in which six of the eight terrestrial RAPs, and associated soil samples, were collected from a site located in a managed coniferous forestry plantation in north-west England. Adult life stages of species representing six of the terrestrial RAPs (Wild grass, Pine tree, Deer, Rat, Earthworm and Bee) were sampled and analysed to determine concentrations of 60 elements and gamma-emitting radionuclides. The resultant data have been used to derive concentration ratios (CR(wo-soil)) relating element/radionuclide concentrations in the RAPs to those in soil. This paper presents the first-reported transfer parameters for a number of the RAP-element combinations. Where possible, the derived CR(wo-soil) values are compared with the ICRPs-recommended values and any appreciable differences discussed.

Statin use in primary inflammatory breast cancer: a cohort study.

BACKGROUND: Some studies have suggested that statins, which have cholesterol-lowering and anti-inflammatory properties, may have antitumor effects. Effects of statins on inflammatory breast cancer (IBC) have never been studied. METHODS: We reviewed 723 patients diagnosed with primary IBC in 1995-2011 and treated at The University of Texas MD Anderson Cancer Center. Statin users were defined as being on statins at the initial evaluation. Based on Ahern et al's statin classification (JNCI, 2011), clinical outcomes were compared by statin use and type (weakly lipophilic to hydrophilic (H-statin) vs lipophilic statins (L-statin)). We used the Kaplan-Meier method to estimate the median progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS), and a Cox proportional hazards regression model to test the statistical significance of potential prognostic factors. RESULTS: In the multivariable Cox model, H-statins were associated with significantly improved PFS compared with no statin (hazard ratio=0.49; 95% confidence interval=0.28-0.84; P<0.01); OS and DSS P-values were 0.80 and 0.85, respectively. For L-statins vs no statin, P-values for PFS, DSS, and OS were 0.81, 0.4, and 0.74, respectively. CONCLUSION: H-statins were associated with significantly improved PFS. A prospective randomised study evaluating the survival benefits of statins in primary IBC is warranted.

Chornobyl radiation spikes are not due to military vehicles disturbing soil.

On 25th February 2022, increased gamma radiation dose rates were reported within the Chornobyl Exclusion Zone (CEZ). This coincided with Russian military vehicles entering the Ukrainian part of the CEZ from neighbouring Belarus. It was speculated that contaminated soil resuspension by vehicle movements or a leak from the Chornobyl Nuclear Power Plant complex may explain these spikes in radiation dose rates. The gamma dose rate monitoring network in the CEZ provides a crucial early warning system for releases of radioactivity to the environment and is part of the international safeguards for nuclear facilities. With the potential for further military action in the CEZ and concerns over nuclear safety, it is essential that such anomalous readings are investigated. We evaluate the hypotheses suggested to explain the apparent gamma dose rate increases, demonstrating that neither military vehicle-induced soil resuspension nor a leak from the Chornobyl Nuclear Power Plant are plausible. However, disruption of the Chornobyl base-station's reception of wireless signals from the gamma dose rate monitoring network in the CEZ may potentially explain the dose rate increases recorded.

Avian predators taste reject mimetic prey in relation to their signal reliability.

Aposematic organisms defend themselves through various means to increase their unprofitability to predators which they advertise with conspicuous warning signals. Predators learn to avoid aposematic prey through associative learning that leads to lower predation. However, when these visual signals become unreliable (e.g., through automimicry or Batesian mimicry), predators may switch from using visual signals to taste sampling prey to choose among them. In this experiment, we tested this possibility in a field experiment where we released a total of 4800 mealworm prey in two clusters consisting of either: (i) undefended prey (injected with water) and (ii) model-mimics (injected with either quinine sulphate [models] or water [mimics]). Prey were deployed at 12 sites, with the mimic frequency of the model-mimics ranging between 0 and 1 (at 0.2 intervals). We found that taste rejection peaked at moderate mimic frequencies (0.4 and 0.6), supporting the idea that taste sampling and rejection of prey is related to signal reliability and predator uncertainty. This is the first time that taste-rejection has been shown to be related to the reliability of prey signals in a mimetic prey system.

Spring-mass behavioural adaptations to acute changes in prosthetic blade stiffness during submaximal running in unilateral transtibial prosthesis users.

BACKGROUND: Individuals with lower-limb amputation can use running specific prostheses (RSP) that store and then return elastic energy during stance. However, it is unclear whether varying the stiffness category of the same RSP affects spring-mass behaviour during self-selected, submaximal speed running in individuals with unilateral transtibial amputation. RESEARCH QUESTION: The current study investigates how varying RSP stiffness affects limb stiffness, running performance, and associated joint kinetics in individuals with a unilateral transtibial amputation. METHODS: Kinematic and ground reaction force data were collected from eight males with unilateral transtibial amputation who ran at self-selected submaximal speeds along a 15 m runway in three RSP stiffness conditions; recommended habitual stiffness (HAB) and, following 10-minutes of familiarisation, stiffness categories above (+1) and below (-1) the HAB. Stance-phase centre of mass velocity, contact time, limb stiffness' and joint/RSP work were computed for each limb across RSP stiffness conditions. RESULTS: With increased RSP stiffness, prosthetic limb stiffness increased, whilst intact limb stiffness decreased slightly (p<0.03). Centre of mass forward velocity during stance-phase (p<0.02) and contact time (p<0.04) were higher in the intact limb and lower in the prosthetic limb but were unaffected by RSP stiffness. Intact limb hip joint positive work increased for both the +1 and -1 conditions but remained unchanged across conditions in the prosthetic limb (p<0.02). SIGNIFICANCE: In response to changes in RSP stiffness, there were acute increased mechanical demands on the intact limb, reflecting a reliance on the intact limb during running. However, overall running speed was unaffected, suggesting participants acutely adapted to an RSP of a non-prescribed stiffness.

A cross-sectional study of gender differences in quality of life domains in patients with neurofibromatosis type 1.

BACKGROUND: There is limited data regarding gender differences in quality of life between women and men with Neurofibromatosis type 1. We aimed to study differences in quality of life domains between women and men with Neurofibromatosis type 1 living in Canada. METHODS: This is a cross sectional study of adults with Neurofibromatosis type 1 attending a tertiary NF centre at Toronto General Hospital between January 2016 to December 2017. Demographic and clinical data were collected. We compared scores of generic measures (SF-36, EQ-5D-5L, pain interference) and a disease-specific measure (PedsQL-NF1 module) between women and men. We also assessed the relationship between disease visibility scored by an examiner (Ablon's visibility index) and self-reported perceived physical appearance, stratified by gender. RESULTS: One hundred and sixty-two participants were enrolled, 92 females and 70 males. Ablon's index score 1 was in 43% and score 2 in 44%, while only 13% of patients had a score 3. Women had worse scores on the total PedsQL-NF1 scales, and also in the perceived physical appearance, anxiety and emotional health domains. In women, there was a low but significant correlation between Ablon's index and perceived physical appearance (r = - 0.27, p = 0.01, ANOVA p < 0.001). In men, there was no difference in self-reported physical appearance by Ablon's index. There were no differences between men and women in the SF-36 or EQ-5D-5L scores. CONCLUSION: Women with NF1 reported worse NF1-related quality of life than men, with worse perceived physical appearance, anxiety, and mental health. Perceived physical appearance does not always correlate to disease visibility; therefore, healthcare providers should inquire about body image, physical appearance concerns, and mental health, especially among women with NF1.

Robot assisted laparoscopic prostatectomy. Striving for Trifecta outcomes in localised prostate cancer.

Radical prostatectomy (RP) is the gold standard treatment for localised prostate cancer and its oncological effectiveness has been demonstrated so far. With no doubt though, RP has significant potential morbidity and the selection of patients who will likely benefit from surgery while minimising the side effects of incontinence and erectile dysfunction is fundamental. Robot-assisted radical prostatectomy allows us to achieve oncological control, early continence and preservation of erectile function all in one. Thus, analysing its role is of utmost importance.

Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes.

The receptor for macrophage colony stimulating factor (CSF-1), the c-fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c-ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms proximal promoter. On the other hand c-myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-fms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c-myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-fms mRNA. The repressor function of c-myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-fms and that c-myb acts to ensure correct temporal expression of c-fms during myeloid differentiation.