The Spider: a visual, multisystemic symptom impact questionnaire for people with hypermobility-related disorders-validation in adults.

INTRODUCTION: Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are often accompanied by varied and complex multisystemic comorbid symptoms/conditions. The Spider questionnaire was developed to evaluate the presence and impact of eight common multisystemic comorbidities. Thirty-one questions across eight symptom domains assess neuromusculoskeletal, pain, fatigue, cardiac dysautonomia, urogenital, gastrointestinal, anxiety, and depression symptoms. This study aimed to evaluate the Spider's construct validity in adults. METHOD: A cross-sectional observational study was conducted over four stages. Three international patient charities aided recruitment of participants through social media and website advertisements. Adults aged 18 to 65 years, with and without HSD/hEDS, were invited to participate. Validated, frequently used comparator questionnaires were used to establish convergent validity of Spider symptom domains. A control group was recruited for known-group validity analysis. Participants answered each Spider domain and the corresponding comparator questionnaire via surveys hosted by REDCap. Anonymous data were analysed using SPSS. Convergent validity was assessed through Spearman's correlational analysis and known-group validity through Mann-Whitney U analysis. RESULTS: A total of 11,151 participants were recruited across the four stages. Statistically significant, moderate-to-strong correlations were found between all Spider domains and their comparators (p < 0.001, r = 0.63 to 0.80). Known-group validity analysis showed statistically significant differences (p < 0.001) between the hypermobile and control groups in all eight domains. CONCLUSIONS: Convergent and known-group validity of the Spider was established with adults. These results suggest the Spider can measure the presence and impact of multisystemic comorbid symptoms/conditions in adults with HSD/hEDS, providing a tool which guides multidisciplinary management. Key Points • The Spider questionnaire is a novel tool assessing the presence and impact of the multisystemic comorbid symptoms/conditions associated with HSD/hEDS. • Convergent and known-group validity of the Spider questionnaire was established in adults aged 18 to 65. • This tool provides a quick and easy method to visualise the symptom profile of those with HSD/hEDS to guide symptom management.

Xenon tracers for cost effective laser induced fluorescence of alternative propellant Hall thrusters.

One of the limiting factors to developing plasma thrusters on alternative propellants is the cost associated with changing the diagnostic tools, which are often propellant-dependent. For laser induced fluorescence (LIF), which is typically used for ion velocity distribution measurements to determine ion trajectories and potential profiles, either new lasers need to be bought, which are tuned to the wavelength of the new element's excitation level, or a costly tunable laser is required. A method to use existing LIF setups designed for xenon on any propellant has been demonstrated on a Hall thruster operating on krypton. In the demonstration test, a small amount of xenon (0.01%-4%) was mixed with the main krypton propellant for use as a diagnostic tracer, and xenon ion velocities were measured while also monitoring changes in the mean discharge current and oscillations. High signal-to-noise ratios in LIF data acquired along the channel centerline were obtained with tracer gas fractions ≤1% that negligibly affected the thruster operation. These results and comparison of the emission spectra of xenon and other common propellants suggest that the tracer LIF method should be broadly applicable to LIF measurements in Hall thrusters operating on alternative propellants.

Masterclass: Hypermobility and hypermobility related disorders.

INTRODUCTION: Hypermobile joints display a range of movement that is considered excessive, taking into consideration the age, gender and ethnic background of the individual. Joint hypermobility may present in a single joint, a few joints or in multiple joints and may be congenital or acquired with training, disease or injury. Hypermobile joints may be asymptomatic or may be associated with pain, fatigue, multisystemic complaints and significant disability. Furthermore, joint hypermobility may be a sign of an underlying hereditary disorder of connective tissue. PURPOSE: This masterclass aims to provides a state-of-the-art review of the aetiology, epidemiology, clinical presentation, assessment and management of joint hypermobility and hypermobility related disorders using an evidence based and biopsychosocial approach. The new framework for classifying the spectrum of joint hypermobility disorders along with new diagnostic criteria for the hypermobile Ehlers Danlos syndrome, published by an international consortium of clinical experts and researchers in 2017 is integrated into the paper. IMPLICATIONS FOR PRACTICE: People with joint hypermobility related disorders present to healthcare professionals with a wide range of symptoms which extend beyond the musculoskeletal system. Early recognition and treatment are key to effective management. A biopsychosocial and patient empowerment approach to functional restoration is recommended.

The use of dose quantities in radiological protection: ICRP publication 147 Ann ICRP 50(1) 2021.

The International Commission on Radiological Protection has recently published a report (ICRP Publication 147;Ann. ICRP50, 2021) on the use of dose quantities in radiological protection, under the same authorship as this Memorandum. Here, we present a brief summary of the main elements of the report. ICRP Publication 147 consolidates and clarifies the explanations provided in the 2007 ICRP Recommendations (Publication 103) but reaches conclusions that go beyond those presented in Publication 103. Further guidance is provided on the scientific basis for the control of radiation risks using dose quantities in occupational, public and medical applications. It is emphasised that best estimates of risk to individuals will use organ/tissue absorbed doses, appropriate relative biological effectiveness factors and dose-risk models for specific health effects. However, bearing in mind uncertainties including those associated with risk projection to low doses or low dose rates, it is concluded that in the context of radiological protection, effective dose may be considered as an approximate indicator of possible risk of stochastic health effects following low-level exposure to ionising radiation. In this respect, it should also be recognised that lifetime cancer risks vary with age at exposure, sex and population group. The ICRP report also concludes that equivalent dose is not needed as a protection quantity. Dose limits for the avoidance of tissue reactions for the skin, hands and feet, and lens of the eye will be more appropriately set in terms of absorbed dose rather than equivalent dose.

Health promotion: How government can ensure that the National Health Insurance Fund has a fighting chance.

Health promotion - keeping people healthy - is critical to ensuring that South Africa (SA)'s National Health Insurance (NHI) services and funding will not be overwhelmed by having to service and pay for large numbers of people with avoidable disease. Although the 2019 NHI Bill mentions health promotion, its lack of emphasis and the narrow approach proposed in the Bill make it unlikely that health promotion will have significant impact on population health or reducing healthcare need. Health promotion experts submit that there is in fact huge potential for carefully planned and researched health promotion to impact on population health. The establishment of a multisectoral National Health Commission or an independent Health Promotion and Development Foundation linked directly to the NHI Fund that includes several relevant government departments and civil society and researchers is proposed. Of the NHI Fund, 2% should be dedicated specifically to promoting health and preventing illness, which must support comprehensive, multisectoral health promotion interventions that go beyond awareness raising and health education. SA's specific realities and needs, including poverty and its related behavioural impacts and health consequences, must be taken into account.

Comparative Study of Pediatric Coronary Allograft Vasculopathy Between Single Centers in North America and United Kingdom.

BACKGROUND: Coronary allograft vasculopathy (CAV) is the leading cause of death after pediatric heart transplantation from 1 year postoperation. Anecdotal evidence suggests a difference in the severity of disease between UK and North America. We performed a comparative study using intravascular ultrasound (IVUS). METHODS: Consecutive IVUS procedures from a single year were included from each center. Using standardized techniques, measurement of the vessel area, lumen area, and maximal intimamedial thickening (IMT) were performed with calculation of intimal index (II) for each slice. Mean II, mean IMT, and absolute maximum IMT were calculated along the left coronary artery for each patient. Transplant demographics and treatment details were included in the analysis. RESULTS: One hundred four patients were included between the 2 centers. Interobserver variability for IVUS analysis was excellent. Patients were aged mean 14.2 (SD 3.3) years at the time of the study and 9.2 (SD 6.0) years earlier post-transplant procedure. UK patients were older, at transplant for a shorter time, and demonstrated more severe CAV. Multiple regression analysis demonstrated the detrimental effect of donor age and time from transplant on CAV severity and benefits of sirolimus use. CONCLUSIONS: The data show more severe CAV in the UK cohort despite significantly shorter time post-transplant. Donor age and time post-transplant were associated with more severe CAV and sirolimus use was associated with a reduction in IMT. This study demonstrates a marked difference in the prevalence of CAV in children between UK and North America. The causes are likely to be multifactorial; however, younger donors and recipients have significantly less disease.

Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a service setting.

BACKGROUND: Muir-Torre syndrome (MTS) is a subtype of Lynch syndrome, which encompasses the combination of sebaceous skin tumours or keratoacanthomas and internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous neoplasms (SNs) may occur before other malignancies, and may lead to the diagnosis, which allows testing of other family members, cancer surveillance, risk-reducing surgery or prevention therapies. AIM: To evaluate the efficacy of universal immunohistochemistry (IHC) screening of SNs in a service setting. METHODS: Patients with SNs were ascertained by a regional clinical pathology service over a 3-year period. Results of tumour IHC, clinical genetics notes and germline genetic testing were retrospectively reviewed. RESULTS: In total, 62 patients presented with 71 SNs; 9 (15%) of these patients had previously diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients (94%); 26 (52%) had loss of staining of one or more mismatch repair proteins. Fifteen patients were referred to the Clinical Genetics department, and 10 patients underwent germline genetic testing. Two had a new diagnosis of MTS confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2 genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old woman with a sebaceous adenoma and history of endometrial cancer; to our knowledge, this is the first time a PMS2 mutation has been reported in MTS. CONCLUSIONS: Universal IHC screening of SNs is an effective method to identify cases for further genetic evaluation. Rates of referral to clinical genetics were only moderate (58%). Increased awareness of MTS could help improve the rate of onward referral.

Successful orthotopic heart transplantation using a donor heart with ALCAPA.

With the imbalance between donation rates and potential recipients growing, transplant programs are increasingly using non-ideal organs from so-called marginal donors. This is the first reported case of the intentional use of a donor heart with ALCAPA. The recipient was aged one yr with restrictive cardiomyopathy who had been supported with BiVAD for over six months. Function of the donor left ventricle was shown to be well preserved, with no obvious signs of ischemia, except for a fibrotic layer on the anterolateral papillary muscle of the mitral valve. To prevent coronary steal, the anomalous left coronary artery ostium from the MPA was oversewn prior to implantation. The transplanted heart spontaneously regained sinus rhythm immediately following cross-clamp release and showed good contractility from the first postoperative echocardiogram. The patient continues to do well 18 months post-transplant, with excellent function on echocardiography, and good flow on coronary angiography.

Use of effective dose.

International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group.

Physiotherapy management of joint hypermobility syndrome--a focus group study of patient and health professional perspectives.

OBJECTIVE: To develop an understanding of patient and health professional views and experiences of physiotherapy to manage joint hypermobility syndrome (JHS). DESIGN: An explorative qualitative design. Seven focus groups were convened, audio recorded, fully transcribed and analysed using a constant comparative method to inductively derive a thematic account of the data. SETTING: Four geographical areas of the U.K. PARTICIPANTS: 25 people with JHS and 16 health professionals (14 physiotherapists and two podiatrists). RESULTS: Both patients and health professionals recognised the chronic heterogeneous nature of JHS and reported a lack of awareness of the condition amongst health professionals, patients and wider society. Diagnosis and subsequent referral to physiotherapy services for JHS was often difficult and convoluted. Referral was often for acute single joint injury, failing to recognise the long-term multi-joint nature of the condition. Health professionals and patients felt that if left undiagnosed, JHS was more difficult to treat because of its chronic nature. When JHS was treated by health professionals with knowledge of the condition patients reported satisfactory outcomes. There was considerable agreement between health professionals and patients regarding an 'ideal' physiotherapy service. Education was reported as an overarching requirement for patients and health care professionals. CONCLUSIONS: Physiotherapy should be applied holistically to manage JHS as a long-term condition and should address injury prevention and symptom amelioration rather than cure. Education for health professionals and patients is needed to optimise physiotherapy provision. Further research is required to explore the specific therapeutic actions of physiotherapy for managing JHS.

Inflammatory Cytokines, Endothelial Function, and Chronic Allograft Vasculopathy in Children: An Investigation of the Donor and Recipient Vasculature After Heart Transplantation.

Chronic allograft vasculopathy (CAV) limits the lifespan of pediatric heart transplant recipients. We investigated blood markers of inflammation, endothelial dysfunction, and damage to both the native and transplanted vasculature in children after heart transplantation. Serum samples were taken from pediatric heart transplant recipients for markers of inflammation and endothelial activation. The systemic vasculature was investigated using brachial artery flow-mediated dilatation and carotid artery intima-medial hyperplasia. CAV was investigated using intravascular ultrasound. Mean intima-media thickness (mIMT) > 0.5 mm was used to define significant CAV. Forty-eight children (25 male) aged 8-18 years were enrolled in the study. Patients were a median (interquartile range) 4.1 (2.2-8.7) years after transplant. Patients had increased levels of circulating IL6 (3.86 [2.84-4.95] vs. 1.66 [1.22-2.63] p < 0.0001), vascular cell adhesion molecule 1 (539 [451-621] vs. 402 [342-487] p < 0.001), intracellular adhesion molecule 1 305 (247-346) vs. 256 (224-294) p = 0.002 and thrombomodulin (7.1 [5.5-8.1] vs. 3.57 [3.03-4.71] p < 0.0001) and decreased levels of tumor necrosis factor-α, E selectin, and P selectin, compared with controls. The systemic vasculature was unaffected. Patients with severe CAV had raised serum von Willebrand factor and decreased serum thrombomodulin. Posttransplant thrombomodulin levels are elevated after transplant but significantly lower in those with mIMT > 0.5 mm. This suggests that subclinical inflammation is present and that natural anticoagulant/thrombomodulin activity is important after transplant.

A case-control study assessing bone mineral density in severe haemophilia A in the UK.

It has been shown that bone mineral density (BMD) may be lower in patients with haemophilia (PWH). A comparison to control subjects is required to thoroughly assess current BMD in PWH in the UK. The objective of this study was to test the hypothesis that BMD is lower in PWH than in controls, and in patients with more severely affected joints or lower activity levels. In this case-control study, 37 patients with severe haemophilia A were recruited from two haemophilia centres in the UK. A group of 37 age, gender and ethnicity-matched control participants were recruited. All participants had a bone density scan, a musculoskeletal assessment, a blood test for vitamin D and completed a functional activity questionnaire. Of the case group, 5% had osteoporosis and 24% had BMD lower than expected for age. No control participants had osteoporosis, 3% had osteopenia and 14% had BMD lower than expected for age. Ninety one per cent of case participants and 92% of control participants had reduced 25(OH)D levels. Case participants had significantly lower BMD than control participants, and case participants with more severely affected joints, lower activity levels, HIV, history of hepatitis C or lower BMI had significantly lower BMD. Patients with severe haemophilia have a higher risk of low BMD than men without haemophilia. Patients with more severely affected joints and lower activity levels have lower BMD. It remains unclear whether patients with low BMD reached adequate peak bone mass. Low vitamin D may be present in the majority of PWH.

ICRP Publication 124: Protection of the Environment under Different Exposure Situations.

In this report, the Commission describes its framework for protection of the environment and how it should be applied within the Commission's system of protection. The report expands upon its objectives in relation to protection of the environment, in so far as it relates to the protection of animals and plants (biota) in their natural environment, and how these can be met by the use of Reference Animals and Plants (RAPs); their Derived Consideration Reference Levels (DCRLs), which relate radiation effects to doses over and above their normal local background natural radiation levels; and different potential pathways of exposure. The report explains the different types of exposure situations to which its recommendations apply; the key principles that are relevant to protection of the environment; and hence how reference values based on the use of DCRLs can be used to inform on the appropriate level of effort relevant to different exposure situations. Further recommendations are made with regard to how the Commission's recommendations can be implemented to satisfy different forms of environmental protection objectives, which may require the use of representative organisms specific to a site, and how these may be compared with the reference values. Additional information is also given with regard to, in particular, communication with other interested parties and stakeholders. Issues that may arise in relation to compliance are also discussed, and the final chapter discusses the overall implications of the Commission's work in this area to date. Appendices A and B provide some numerical information relating to the RAPs. Annex C considers various existing types of environmental protection legislation currently in place in relation to large industrial sites and practices, and the various ways in which wildlife are protected from various threats arising from such sites.

Michael J. Simmonds1, Herbert J. Meiselman2, Oguz K. Baskurt3 / 老年心脏病学杂志（英文版）

The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals;this finding of increased fibrinogen concen-tration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.

Susceptibility to Fusarium head blight is associated with the Rht-D1b semi-dwarfing allele in wheat.

Fusarium head blight (FHB) is an important disease of wheat worldwide. The cultivar Spark is more resistant than most other UK winter wheat varieties but the genetic basis for this is not known. A mapping population from a cross between Spark and the FHB susceptible variety Rialto was used to identify quantitative trait loci (QTL) associated with resistance. QTL analysis across environments revealed nine QTL for FHB resistance and four QTL for plant height (PH). One FHB QTL was coincident with the Rht-1D locus and accounted for up to 51% of the phenotypic variance. The enhanced FHB susceptibility associated with Rht-D1b is not an effect of PH per se as other QTL for height segregating in this population have no influence on susceptibility. Experiments with near-isogenic lines supported the association between susceptibility and the Rht-D1b allele conferring the semi-dwarf habit. Our results demonstrate that lines carrying the Rht-1Db semi-dwarfing allele are compromised in resistance to initial infection (type I resistance) while being unaffected in resistance to spread within the spike (type II resistance).

Review of trends in the UK population dose.

The Radiation Protection Division of the Health Protection Agency (HPA-RPD), formerly the National Radiological Protection Board, has periodically reported the doses to members of the public and workers in the UK from all sources of radiation. This paper is a review of the doses reported in these publications from the 1970s to 2000 or later. The paper aims to present how the estimated doses received by the UK population have changed over this time period, and where possible from earlier years as well, from all sources of radiation. It was not possible to directly compare the doses reported in the earlier reports. There have been changes in the type of doses estimated, the dosimetry (in particular the definition of effective dose) and improvements made in the measurement of natural background doses. In these cases the earlier reported doses have been recalculated using modern dosimetry so that the doses can be compared. The occupational doses reported in this paper are for those workers involved in the civil nuclear power production industry, industrial radiography or from the medical use of radiation sources. For workers it was found that the individual and collective dose has decreased significantly over this time through the introduction of legislation, the improvement in technology and better working practices. Members of the public are exposed to radiation following the atmospheric testing of nuclear weapons, discharges from UK civil nuclear sites and from diagnostic radiology as well as from natural sources. Exposure to anthropogenic sources has decreased over the period considered in this paper. However, the dose to the UK population as a whole, presented as a per caput dose to a population of 55 million, has not changed significantly as it is dominated by the constant level of exposure to natural sources of radiation.

The combined impact on doses to man of multiple, authorized, radionuclide discharges for the year 1999 reaching the upper river thames, uk.

Before issuing a new or revised authorization to discharge liquid radioactive waste to a river, past and current practice has been to assess the impact of each discharge on a site-by-site basis. This paper reports an assessment of the combined impact of all the (year 1999) authorized discharges in the upper River Thames (UK) catchment. A modification of the PC-CREAM model, using parameters specific to the upper River Thames, was used to estimate "potential doses" to the population, using the authorized discharge activity for each of the discharges as the main driving variable. The main purpose of this study was to investigate the difference in doses between single and multiple discharges in the Thames. A partial validation of the model against measurements was also carried out as a secondary investigation. The source term of the upper Thames consisted of 90 authorized discharges for 86 sites, made up of three nuclear licensed sites, 36 industrial discharges, 25 research organizations, 20 hospitals and two miscellaneous organizations. Of the authorized discharges, nuclear sites constituted 67% of the total activity in authorizations to discharge; hospitals 16%, research organizations 13%, and industry only 3%. Three radionuclides made up 96% of the total authorized discharge activity: tritium-74%; Tc-15%, and C-7%. No other single radionuclide constituted more than 1.5% of the total activity. All of the discharges from non-nuclear sites were via a sewage works so that, in total, only 39 discrete discharges to the river were included in the model. For the purposes of the assessments, it was assumed that all discharges were at the authorized limits (rather than using actual discharge). Even with this maximizing assumption, all the calculated potential doses from the combined source terms were significantly less than the radiation dose limit of 1 mSv y for a member of the public. The highest estimated potential doses were investigated further to identify the major pathways. Ingestion of fish was the main pathway in several river stretches and in the highest case constituted 97% of the dose. In a few stretches, external irradiation from the riverbank or ingestion of drinking water were the main pathways, but the potential contribution was a very small percentage (<1%) of the dose limit for members of the public. An investigation of the reasons for the relatively high potential doses resulting from fish showed that the radionuclide with the largest contribution was P. Three factors had a major effect on potential dose estimations in these circumstances: the fish consumption rate, the P concentration factor and the use of P in some cases to represent radionuclides authorized for discharge as "any other radionuclide, except alpha emitters." Using the precautionary principle, all authorized activity in the latter designation was modeled as the radionuclide which would produce the highest dose to humans.