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Objectives This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. Methods Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria. Results At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). Conclusion In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes.

Nailplated timber trusses are widely used in residential housing. However, there is limited evidence of use or research on the application of nailplated trusses in exposed environments. It is common knowledge to the nailplated truss industry that weather-exposed trusses experience a phenomenon referred to as “nailplate backout”, where the nailplates separate from the timber surface due to the shrink-swell mechanism of the timber in response to its varying moisture content. This paper investigates the performance of innovative nailplated joints on: (1) stopping moisture-driven backout and (2) increasing the capacity of the joints, when compared to currently used joints, after exposure to severe moisture cycling. Three different experimental sets of joints were manufactured to achieve these outcomes, with Set 1 and Set 2 containing 100 splice and 100 butt joints while Set 3 had 40 splice and 40 butt joints. Sets 1 and 2 have a re-designed tooth profile where: (1) Set 1 combined a polyurethane adhesive with a modified nailplate tooth designed to allow the adhesive to penetrate the timber and (2) Set 2 implemented a hook in the middle of the nailplate teeth to grab the timber when the nailplate tries to separate from the timber, either from moisture induced backout or from loading. Polyurethane adhesive was also used in Set 3 but on an un-modified tooth profile. To evaluate the efficiency of the new nailplates, control joints with unmodified nailplates were manufactured for each set and tested. All joints were subjected to severe accelerated moisture cycles inside an air-driven kiln with the temperature being kept constant 70 °C and the relative humidity varied between 15 and 95%. The cycles consisted of a 7-h wetting and an 18-h drying period. For Sets 1 and 2, the tensile capacity of the joints was measured after 0, 3, 6, 9 and 12 moisture cycles, while for Set 3, it was only measured after 0 and 12 cycles. The backout was recorded after each moisture cycle for Sets 1 and 2 and after 12 cycles for Set 3. The average backout of Set 1 and Set 2 control joints after 12 severe cycles was 1.13 mm and 1.01 mm, respectively, while the addition of glue and a hook reduced the backout to 0.56 and 0.92 mm, respectively. In terms of capacity, the adhesive in Set 1 increased the capacity for the splice joints and butt joints by 43% and 13%, respectively. In Set 2, the hook only marginally increased the capacity of the splice joints by 13% and reduced the average butt joint capacity. Observations were made regarding the failure modes of the joints. The addition of the adhesive and hook to the nailplate teeth resulted in more joints failing due to the capacity of the timber rather than due to the nailplate separating from the timber during the tensile testing.

Purpose of Review Juvenile-onset systemic lupus erythematosus ((j)SLE) is an autoimmune/inflammatory disease that results in significant damage and disability. When compared to patients with disease onset in adulthood, jSLE patients exhibit increased disease activity, damage and require more aggressive treatments. This manuscript summarises age-specific pathogenic mechanisms and underscores the need for age group–specific research, classification and treatment. Recent Findings Genetic factors play a significant role in the pathophysiology of jSLE, as > 7% of patients develop disease as a result of single gene mutations. Remaining patients carry genetic variants that are necessary for disease development, but require additional factors. Increased ‘genetic impact’ likely contributes to earlier disease onset and more severe phenotypes. Epigenetic events have only recently started to be addressed in jSLE, and add to the list of pathogenic mechanisms that may serve as biomarkers and/or treatment targets. To allow meaningful and patient-oriented paediatric research, age-specific classification criteria and treatment targets require to be defined as currently available tools established for adult-onset SLE have limitations in the paediatric cohort. Summary Significant progress has been made in understanding the pathophysiology of jSLE. Meaningful laboratory and clinical research can only be performed using age group–specific tools, classification criteria and treatment targets.

Objective We sought to explore patient and parental views on treatment targets, outcome measures and study designs being considered for a future JSLE treat-to-target (T2T) study. Methods We conducted topic-guided, semistructured interviews with JSLE patients and parents and analysed the audio recorded interviews using thematic approaches. Results Patients and parents differed regarding symptoms they felt would be tolerable, representing ‘low disease activity’. Patients often classed symptoms that they had previously experienced, were ‘invisible’ or had minimal disruption on their life as signs of low disease activity. Parents were more accepting of visible signs but were concerned about potential organ involvement and symptom severity. Overall, patients and parents preferred that children were entirely asymptomatic, with no ongoing treatment side effects. They regarded fatigue as particularly challenging, requiring proper monitoring using a fatigue patient-reported outcome measure. Most families felt that reducing corticosteroids would also be a good treatment target. Overall, families liked the concept of T2T, commenting that it could help to improve disease control, help structure treatment and improve communication with clinicians and treatment compliance. They were concerned that T2T might increase the frequency of hospital visits, thus impacting upon schooling, parental employment and finances. Families made suggestions on how to modify the future trial design to mitigate such effects. Conclusion This study provides guidance from patients and parents on T2T targets and study designs. Complementary quantitative studies assessing the achievability and impact of different targets (e.g. lupus low disease activity state or remission) are now warranted to inform an international consensus process to develop treatment targets.

There is a lack of awareness of paediatric rheumatic diseases (PRDs), among the public, and certain groups of healthcare professionals (HCPs), including general practitioners. To help improve international awareness and understanding of PRDs, World yOung Rheumatic Diseases (WORD) Day was established on 18 March 2019. Its aim was to raise awareness of PRDs and the importance of timely referral plus early diagnosis and access to appropriate treatment and support. A steering committee was established, and an external agency provided digital support. A social media campaign was launched in December 2018 to promote it, and analytics were used to measure its impact. Face-to-face and virtual events took place globally on or around WORD Day 2019, with 34 countries reporting events. Examples included lectures, social gatherings and media appearances. A total of 2585 and 660 individuals followed the official Facebook and Twitter accounts respectively, up until WORD Day. The official #WORDDay2019 hashtag was seen by 533,955 unique accounts on 18 March 2019 alone, with 3.3 million impressions. WORD Day 2019 was the first international campaign focused solely on PRDs. It demonstrated that despite awareness events being often resource-light, they can be implemented across a range of diverse settings. WORD Day has now become an annual global awareness event, facilitated by a growing network of patient, parent and professional community supporters.

In this article we describe the scanning electron microscopy (SEM) techniques of electron channelling contrast imaging and electron backscatter diffraction. These techniques provide information on crystal structure, crystal misorientation, grain boundaries, strain and structural defects on length scales from tens of nanometres to tens of micrometres. Here we report on the imaging and analysis of dislocations and sub-grains in nitride semiconductor thin films (GaN and AlN) and tungsten carbide-cobalt (WC-Co) hard metals. Our aim is to illustrate the capability of these techniques for investigating structural defects in the SEM and the benefits of combining these diffraction-based imaging techniques.

Objectives ∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE. Methods A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment. Results Urine levels of transferrin (P Conclusions Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.

Background Sjögren's syndrome is an inflammatory disorder involving the exocrine glands, characterised by dry eyes and mucosal surfaces, fatigue and arthralgia. Sjögren's may occur in isolation (primary) or secondary to another autoimmune condition and is considered rare in the paediatric population (incidence and prevalence unknown). Anecdotal reports of differences in clinical presentation and absence of validated paediatric classification criteria render reliable diagnosis challenging and optimal treatment pathways difficult to ascertain. The American-European Consensus Group (AECG) criteria are considered gold standard for diagnosis of primary Sjogren’s syndrome in adults. A 2017 BSR Sjögren's guideline recommends treating children according to the adult pathway. We report a multicentre service evaluation exploring the presentation and management of children with Sjögren's presenting to UK paediatric rheumatology services, with reference to existing adult criteria. Methods Retrospective study conducted using a standardised data collection proforma under local service evaluation permissions. Inclusion criteria: pre-existing diagnosis of either primary or secondary Sjögren's syndrome under 16 years of age. Each case was assessed against the current adult criteria and guidance (AECG and BSR). Results 20 patients (16 female) in eight UK centres with a mean age at diagnosis of 11 (range 2-16 years). 15 patients had primary Sjögren's, 3 secondary Sjögren's and 2 were not categorised. No primary Sjögren's patients fulfilled AECG diagnostic criteria. Dry eye symptoms were present in 13%, dry mouth symptoms in 53% and 14/15 patients were tested for anti Ro/La (100% anti-Ro positive, 43% anti-La positive). Objective ocular dryness (Schirmers or van Bijsterveld positive), objective oral dryness and labial gland focus score were not formally assessed in any patients. No primary Sjögren's patients fulfilled ACR EULAR diagnostic criteria and one patient fitted exclusion criteria. The most common primary Sjögren's symptoms included parotid pain or swelling (73%), dry mouth (53%), arthralgia (47%) and fatigue (40%). Rash and headaches were also described whereas fever and lymphadenopathy were not reported. Sicca symptoms were reported in 100% secondary Sjogren’s patients (66% had parotid pain or swelling.) Management of all patients was assessed against 2017 BSR guidelines. There was documented evidence in 75% of receiving education, diet and lifestyle advice. 50% were prescribed moisturising eye drops. Hydroxychloroquine treatment was considered in 75%; of these, 4% were not referred for annual eye screening. Conclusion Sjögren's syndrome is rare in children and specific paediatric guidance does not exist. Despite extensive investigations no primary Sjögren's patients fulfilled the AECG or ACR EULAR diagnostic criteria due to difficulty in obtaining objective evidence of oral or ocular dryness. These data suggest that primary paediatric presentations may differ from adult cohorts with frequent parotid pain or swelling and less self-reporting of sicca symptoms. Further work is needed to support development of paediatric specific guidelines for Sjögren's syndrome. Disclosures R. Close None. A. Lant None. E. Smith None. C.M. Anderson None. S. Deepak None. R. Foster None. K. Haslam None. L. Bray None. P. Dawson None. C. Bhat None. F. McErlane None.

© 2018 Elsevier Ltd. The systemic autoimmune/inflammatory condition systemic lupus erythematosus (SLE) manifests before the age of 16 years in 10-20% of all cases. Clinical courses are more severe, and organ complications are more common in patients with juvenile SLE. Varying gender distribution in different age groups and increasing severity with younger age and the presence of monogenic disease in early childhood indicate distinct differences in the pathophysiology of juvenile versus adult-onset SLE. Regardless of these differences, classification criteria and treatment options are identical. In this article, we discuss age-specific pathomechanisms of juvenile-onset SLE, which are currently available and as future treatment options, and propose reclassification of different forms of SLE along the inflammatory spectrum from autoinflammation to autoimmunity.

Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus (JSLE) patients. The value of commonly available biomarkers, such as anti-dsDNA antibodies, complement (C3/C4), ESR and full blood count parameters in the identification of active LN remains uncertain. Methods Participants from the UK JSLE Cohort Study, aged Results A total of 370 patients were recruited; 191 (52%) had active LN and 179 (48%) had inactive LN. Binary logistic regression modeling demonstrated a combination of ESR, C3, white cell count, neutrophils, lymphocytes and IgG to be best for the identification of active LN (area under the curve 0.724). Conclusions At best, combining common classic blood biomarkers of lupus activity using multivariate analysis provides a ‘fair’ ability to identify active LN. Urine biomarkers were not included in these analyses. These results add to the concern that classic blood biomarkers are limited in monitoring discrete JSLE manifestations such as LN.

Background: In the series of talks ‘How to manage and treat childhood onset lupus? A multidisciplinary point of view” the first talk focuses on achievement of the initial diagnosis of Lupus within the childhood period, including some potential pitfalls and how these can be avoided. Initial and ongoing treatment within the childhood period, alongside paediatric specific therapeutic considerations will be discussed. The role of the multidisciplinary team of doctors, nurses, physiotherapists, occupational therapists, psychologists and sub-specialists will be highlighted. The impact of the diagnosis on the child, family, education and social activities will also be described. This talk will be followed by a subsequent talks following the patient through transition and into adulthood. Disclosure of Interests: None declared

Background The incidence of Juvenile-onset Systemic Lupus Erythematosus (JSLE) in the UK is not well described. Furthermore, we do not know how children and young people initially present and when and where they access care. Previous work has described significant variation in time to diagnosis for UK patients1. Objectives To describe how patients with JSLE currently present, are diagnosed and managed across the UK. Methods Data was collected over 13 months on all children (aged Results 102 cases were reported from Sept 2017–Oct 18. 65 cases were excluded (duplicate cases, diagnosis date outside study period, case definition not met, clinical data pending) and 37 included. All patients met SLICC-2012 and 35 patients met ACR-1997. Of the two patients meeting SLICC-2012 but not ACR-1997, one had lupus nephritis on renal biopsy and positive ANA, and the other met the SLICC-2012 hypocomplementaemia criterion. Of the 35 patients meeting ACR-1997, median age at diagnosis was 12.8 years (interquartile range (IQR) 11.8–14.7 years) with female:male gender of 4.8:1 respectively. 24/35 (69%) were non-Caucasian. Median time from symptom onset to diagnosis was 2 months (IQR 1–6 months). The longest delay was 106 months (patient initially diagnosed with Henoch Schnolein Purpura). 9/35 (26%) of patients experienced a delay in diagnosis measured by at least one of: established organ damage due to JSLE at diagnosis (5 patients), review by ≥1 paediatric sub-specialist prior JSLE diagnosis (3 patients) or patient not referred despite medical review (6 patients). The diagnosis was made by or in conjunction with paediatric rheumatology in 21/35 (60%) patients. 4/35 (11%) patients were diagnosed solely by paediatric nephrology, 2/35 (6%) by adult rheumatology, 7/35 (20%) by general paediatrics and 1/35 (3%) by the paediatric infectious diseases team. Of the 12/35 (34%) patients where diagnosis did not involve a rheumatologist 10 were referred to either adult or paediatric rheumatology and 2 patients were managed solely by paediatric nephrology. 31/35 (89%) patients were treated with oral and/or IV steroids and 33/35 (94%) with hydroxychloroquine. Other treatments used were: mycophenolate mofetil (17/35, 49%); rituximab (8/35, 23%); azathioprine (6/35, 17%); methotrexate (5/35, 14%); cyclophosphamide (3/35, 9%); ofatumumab (1/35, 3%); IV immunoglobulin (1/35, 3%); plasmapheresis (1/35, 3%). No patients died within one month of diagnosis. Conclusion Diagnosis of JSLE involved paediatric rheumatology in 60% of cases. Median time to diagnosis from symptom onset is two months but there is significant variation; future work will focus on factors influencing this. Analysis of final data (2 year incidence data) will facilitate estimation of current UK incidence rate and description of factors affecting time to diagnosis. References [1] Smith EMD, Foster HE, Gray WK, Taylor-Robinson D and Beresford MW. Predictors of access to care in juvenile systemic lupus erythematosus: evidence from the UK JSLE Cohort Study. Rheumatology2014;53:557-61 [2] RCPCH. British Paediatric Surveillance Unit. http://www.rcpch.ac.uk/bpsu (accessed17th January2019) Disclosure of Interests None declared

© 2019 Smith, Lythgoe and Hedrich. Juvenile-onset systemic lupus erythematosus (JSLE) is a rare, heterogeneous multisystem autoimmune disease that can affect any organ, and present with diverse clinical and serological manifestations. Vasculitis can be a feature of JSLE. It more commonly presents as cutaneous vasculitis than visceral vasculitis, which can affect the central nervous system, peripheral nervous system, lungs, gut, kidneys, heart and large vessels. The incidence and prevalence of vasculitis in JSLE has not been well described to date. Symptoms of vasculitis can be non-specific and overlap with other features of JSLE, requiring careful consideration for the diagnosis to be achieved and promptly treated. Biopsies are often required to make a definitive diagnosis and differentiate JSLE related vasculitis from other manifestations of JSLE, vasculopathies and JSLE related antiphospholipid syndrome. Visceral vasculitis can be life threatening, and its presence at the time of JSLE diagnosis is associated with permanent organ damage, which further highlights the importance of prompt recognition and treatment. This review will focus on the presentation, diagnosis, management and outcomes of vasculitis in JSLE, highlighting gaps in the current evidence base.

Background Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts. Methods Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy. Results A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c)

The scanning electron microscopy techniques of electron backscatter diffraction (EBSD), electron channelling contrast imaging (ECCI) and cathodoluminescence (CL) hyperspectral imaging provide complementary information on the structural and luminescence properties of materials rapidly and non-destructively, with a spatial resolution of tens of nanometres. EBSD provides crystal orientation, crystal phase and strain analysis, whilst ECCI is used to determine the planar distribution of extended defects over a large area of a given sample. CL reveals the influence of crystal structure, composition and strain on intrinsic luminescence and/or reveals defect-related luminescence. Dark features are also observed in CL images where carrier recombination at defects is non-radiative. The combination of these techniques is a powerful approach to clarifying the role of crystallography and extended defects on a material’s light emission properties. Here we describe the EBSD, ECCI and CL techniques and illustrate their use for investigating the structural and light emitting properties of UV-emitting nitride semiconductor structures. We discuss our investigations of the type, density and distribution of defects in GaN, AlN and AlGaN thin films and also discuss the determination of the polarity of GaN nanowires.

Background A urinary biomarker panel including alpha-1-acid-glycoprotein (AGP), lipocalin-like-prostaglandin-D-synthase (LPGDS), transferrin and ceruloplasmin demonstrates an ‘excellent’ ability for identifying active lupus nephritis in UK/US children. This study aimed to assess whether this panel identifies active lupus nephritis within the South African Paediatric Lupus Cohort. Methods Juvenile-onset-systemic lupus erythematosus (JSLE) patients aged Results Twenty-three juvenile-onset-systemic lupus erythematosus patients were recruited with a median age of 13.5 years (interquartile range (IQR) 12.7–14.9) and disease duration of 2.6 years (IQR 1.8–4.0). Eighteen healthy controls had a median age of 11.0 years (IQR 10.0–12.0). AGP, LPGDS, transferrin, ceruloplasmin and VCAM-1 were significantly higher in active than in inactive lupus nephritis patients (corrected p-values, all pc c = 1.0). The optimal biomarker combination included AGP, ceruloplasmin, LPGDS and transferrin (area under the curve = 1.0). Conclusions A urinary biomarker panel comprising AGP, ceruloplasmin, LPGDS and transferrin previously validated within UK/US cohorts also performed excellently within a racially distinct South African cohort which displayed more severe lupus nephritis.

Background Juvenile-onset systemic lupus erythematosus (JSLE) patients may develop lupus nephritis (LN) during their initial presentation, or later in their disease. This study aimed to assess whether clinical/demographic factors characterize patients with LN within the United Kingdom JSLE Cohort Study, and whether such factors predict subsequent LN development. Methods Univariate logistic regression modelling compared clinical/demographic factors in patients with and without LN at baseline. For those who subsequently developed LN, Cox proportional-hazard modelling was used to test the association between such factors and time to LN development. Covariates with p Results A total of 121/331 (37%) patients presented with active LN at baseline, with first American College of Rheumatology (ACR) score ( p –16), severe hypertension ( p = 0.0006), proteinuria ( p –16), creatinine ( p = 1.0 × 10–16), erythrocyte sedimentation rate ( p = 1.0 × 10–16), neutrophils ( p –16), complement 3 (C3) ( p = 4.0 × 10–16) and ethnicity ( p = 3.0 × 10–13) differing between those with and without LN. Of the 210 individuals without active LN at baseline, 13 patients had a single visit and were excluded from further analysis. Thirty-four of 197 (17%) developed LN after a median of 2.04 years (interquartile range, 0.8–3.7), with higher ACR scores ( p = 0.014 , hazard ratio (HR) = 1.45, 95% confidence interval (CI) = 1.08–1.95) and lower C3 levels ( p = 0.0082 , HR = 0.27, 95% CI = 0.10–0.68) demonstrated as predictors of subsequent LN. Conclusions Clinical and demographic factors can help to characterize patients at increased risk of LN.

The Paediatric Rheumatology European Society (PReS) has over many years, developed a portfolio of educational activities to address increasing educational needs of workforce and support young clinicians to acquire skills to develop new knowledge and deliver clinical care in the future. These educational activities aim to facilitate growth of paediatric rheumatology and ultimately improve the clinical care for children and families. This article describes the current portfolio of PReS educational activities and their relevance to the international paediatric rheumatology community. ispartof: PEDIATRIC RHEUMATOLOGY vol:16 issue:1 ispartof: location:England status: published

Background A urine ‘biomarker panel’ comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an ‘excellent’ level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. Methods The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort. Monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were also quantified in view of evidence from other longitudinal studies. Serial urine samples were collected during routine care with detailed clinical and demographic data. A Markov Multi-State model of state transitions was fitted, with predictive clinical/biomarker factors assessed by a corrected Akaike Information Criterion (AICc) score (the better the model, the lower the AICc score). Results The study included 184 longitudinal observations from 80 patients. The homogeneous multi-state Markov model of lupus nephritis activity AICc score was 147.85. Alpha-1-acid-glycoprotein and ceruloplasmin were identified to be the best predictive factors, reducing the AICc score to 139.81 and 141.40 respectively. Ceruloplasmin was associated with the active-to-inactive transition (hazard ratio 0.60 (95% confidence interval [0.39, 0.93])), and alpha-1-acid-glycoprotein with the inactive-to-active transition (hazard ratio 1.49 (95% confidence interval [1.10, 2.02])). Inputting individual alpha-1-acid-glycoprotein/ceruloplasmin values provides 3, 6 and 12 months probabilities of state transition. Conclusions Alpha-1-acid-glycoprotein was predictive of active lupus nephritis flare, whereas ceruloplasmin was predictive of remission. The Markov state-space model warrants testing in a prospective clinical trial of lupus nephritis biomarker led monitoring.

Background A urine ‘biomarker panel’ comprising alpha-1-acid-glycoprotein (AGP), ceruloplasmin (CP), transferrin (TF) and lipocalin-like-prostaglandin-D synthase (LPGDS) has been shown to cross-sectionally perform to an ‘excellent’ level for Lupus Nephritis (LN) identification in children.1 Quantification of all four biomarkers by enzyme linked immunoabsorbant assay (ELISA) techniques is time consuming and costly. Therefore, novel methods of biomarker panel quantification are required to facilitate future urine biomarker led monitoring studies. Objectives The main objective was to compare the ability of ELISA and multiplex biomarker quantification techniques to differentiate active versus inactive LN when the biomarkers are considered individually and in combination. Methods The urinary biomarkers were quantified by both ELISA and a newly developed, custom multiplex platform in participants of the UK Juvenile Systemic Lupus Erythematosus (JSLE) Cohort Study. Multiplex assay development involved identification of appropriate antibody pairs, assessment of JSLE urine sample matrix effects and range finding in JSLE patient samples. Patients were categorised as having active LN (renal domain BILAG score of A, B and previous histological confirmation of LN) or inactive LN (renal BILAG score D or E). Firth’s penalised binary regression with AUC ROC analysis was used to compare the ability of multiplex and ELISA assays to detect active LN disease state univariately and in combination. Results Biomarker analysis was undertaken on 54 JSLE patients (13 active, 41 in-active). Assessment of each biomarker univariately demonstrated similar AUC values regardless of the biomarker quantification technique; LPGDS (ELISA AUC 0.826, multiplex AUC 0.829), TF (ELISA AUC 0.829, multiplex AUC 0.996), CP (ELISA AUC 0.901, multiplex AUC 0.983), AGP (ELISA AUC 0.934, multiplex AUC 0.979) (see table 1). Combining the multiplex biomarker data in the same order as the original ELISA based study1 led to a similar progressive increase in AUC as biomarkers were added to the model (optimal model including AGP +CP + LPGDS+TF ELISA AUC=0.951, multiplex=0.995). For all biomarker combinations, the multiplex-derived AUC was higher than the ELISA AUC. Conclusions This new LN urine biomarker panel multiplex assay has been shown to display a comparable ability for active LN disease state identification as compared to existing ELISA techniques. The major advantage to this approach is that it reduces cost, processing time and the volume of sample required, as compared to ELISA techniques, representing a key enabler for future clinical studies. Reference [1] Smith EM, Jorgensen AL, Midgley A, Oni L, Goilav B, Putterman C, Wahezi D, Rubinstein T, Ekdawy D, Corkhill R, et al. International validation of a urinary biomarker panel for identification of active lupus nephritis in children. Pediatr Nephrol2017;32:283–295. Disclosure of Interest None declared

We have developed an online radiative-transfer suite (https://psg.gsfc.nasa.gov) applicable to a broad range of planetary objects (e.g., planets, moons, comets, asteroids, TNOs, KBOs, exoplanets). The Planetary Spectrum Generator (PSG) can synthesize planetary spectra (atmospheres and surfaces) for a broad range of wavelengths (UV/Vis/near-IR/IR/far-IR/THz/sub-mm/Radio) from any observatory (e.g., JWST, ALMA, Keck, SOFIA), any orbiter (e.g., ExoMars, Juno), or any lander (e.g., MSL). This is achieved by combining several state-of-the-art radiative transfer models, spectroscopic databases and planetary databases (i.e., climatological and orbital). PSG has a 3D (three-dimensional) orbital calculator for most bodies in the solar system, and all confirmed exoplanets, while the radiative-transfer models can ingest billions of spectral signatures for hundreds of species from several spectroscopic repositories. It integrates the latest radiative-transfer and scattering methods in order to compute high resolution spectra via line-by-line calculations, and utilizes the efficient correlated-k method at moderate resolutions, while for computing cometary spectra, PSG handles non-LTE and LTE excitation processes. PSG includes a realistic noise calculator that integrates several telescope / instrument configurations (e.g., interferometry, coronagraphs) and detector technologies (e.g., CCD, heterodyne detectors, bolometers). Such an integration of advanced spectroscopic methods into an online tool can greatly serve the planetary community, ultimately enabling the retrieval of planetary parameters from remote sensing data, efficient mission planning strategies, interpretation of current and future planetary data, calibration of spectroscopic data, and development of new instrument/spacecraft concepts., Journal of Quantitative Spectroscopy and Radiative Transfer, submitted

Background Proteinuria is a well-known risk factor for progression of renal dysfunction in a variety of chronic kidney diseases. In adult-onset Systemic Lupus Erytematosus (SLE) patients with lupus nephritis (LN), proteinuria takes a significant period of time to normalise, with proteinuric remission being associated with improved renal survival and reductions in mortality. The length of time required to attain proteinuric remission has not previously been investigated in Juvenile-onset SLE (JSLE). The aim of this study was to elucidate when proteinuric remission occurs, and whether clinical/demographic factors at LN onset bear influence on the time to proteinuric remission. Methods Participants of the UK JSLE Cohort Study and Repository were included if they had active LN (renal biopsy and/or renal British Isles Lupus Assessment Grade (BILAG) score defined active LN) and proteinuria. Univariate Cox proportional hazard regression modelling was used to explore factors associated with time to proteinuric recovery. Covariates with p-value

The development of biological agents with specific immunological targets has revolutionized the treatment of a wide variety of paediatric diseases where traditional immunosuppressive agents have been partly ineffective or intolerable. The increasing requirement for pharmaceutical companies to undertake paediatric studies has provided impetus for studies of biologics in children. The assessment of biological agents in children to date has largely relied upon randomized controlled trials using a withdrawal design, rather than a parallel study design. This approach has been largely used due to ethical concerns, including use of placebo treatments in children with active chronic disease, and justified on the basis that treatments have usually already undergone robust assessment in related adult conditions. However, this study design limits the reliability of the data and can confuse the interpretation of safety results. Careful ongoing monitoring of safety and efficacy in real-world practice through national and international biologics registries and robust reporting systems is crucial. The most commonly used biological agents in children target tumour necrosis factor-α, interleukin-1, interleukin-6 and cytotoxic lymphocyte-associated antigen-4. These agents are most frequently used in paediatric rheumatic diseases. This review discusses the development and assessment of biologics within paediatric rheumatology with reference to the lessons learned from use in other subspecialties.

We present BUSTED, a new approach to identifying gene-wide evidence of episodic positive selection, where the non-synonymous substitution rate is transiently greater than the synonymous rate. BUSTED can be used either on an entire phylogeny (without requiring an a priori hypothesis regarding which branches are under positive selection) or on a pre-specified subset of foreground lineages (if a suitable a priori hypothesis is available). Selection is modeled as varying stochastically over branches and sites, and we propose a computationally inexpensive evidence metric for identifying sites subject to episodic positive selection on any foreground branches. We compare BUSTED with existing models on simulated and empirical data. An implementation is available on www.datamonkey.org/busted, with a widget allowing the interactive specification of foreground branches.

In 2013, the European Union-funded Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) project was initiated to produce consensus evidence-based international guidance for the diagnosis and management of paediatric rheumatic diseases. The need for this stemmed from observations of varying practice between clinicians/centres throughout Europe as a result of the rarity of paediatric rheumatic diseases, and the challenges in undertaking clinical research. Childhood-onset systemic lupus erythematosus (cSLE, also known as juvenile or paediatric SLE) is a rare, multisystem autoimmune disease with potential for significant associated morbidity and mortality. The SHARE recommendations for its diagnosis and treatment were published in June 20171 (box 1).Box 1 ### Resources #### Background on the Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative: #### SHARE childhood-onset systemic lupus erythematosus (cSLE) recommendations: #### SHARE recommendations for other paediatric rheumatic diseases: No previous guidelines or recommendations on the diagnosis and management of cSLE exist. Adult SLE literature2 3 was consulted where there was no evidence in children. A total of 25 recommendations were …

Background Patients attending the UK’s only ‘Centre of Excellence for Childhood Lupus’, routinely attend clinic appointments 3 monthly. During appointments there is pressure for clinicians to review complex medical presentations in a timely manner. As a service we recognise the importance of holistic, multi-disciplinary care and the need to consider the patients’ and families’ priorities in relation to lupus and its management. The challenges faced by patients in asking questions and asserting influence over a medial consultation are widely acknowledged. Aim To develop a ‘screening tool’ to facilitate this process. Method The tool was developed through consultation with patients, parents and the multi-disciplinary team. Age-appropriate versions were developed to facilitate completion by children as well as their parents’. Parents identified concerns regarding their child’s health as well as areas in which they were struggling themselves regarding their child’s health. Patients and their parent were asked to complete the screening questionnaire in the waiting-room before clinic. Their responses were reviewed by clinicians present thus influencing conversations within the appointment. Where appropriate, families could meet with members of the multi-disciplinary team separately. Completed questionnaires were filed within patients’ case notes. Data were collated to inform lupus service development. Results 36 screening tools were completed (19 young people and 17 parents) over a 10 month period. The most frequently reported concerns for young people were: fatigue (81%), appearance (58%) and pain (53%). Among parents, the greatest concerns were their child’s fatigue (65%), pain (65%), emotions (59%), sleep (59%) and support from school (53%). Parent’s concerns for themselves were associated with their child’s future and their emotions about their child’s health (59%). Conclusion Questionnaires received positive feedback from service-users and staff regarding ease of completion, utility for highlighting issues for discussion within clinic or otherwise and value in normalising the role of psychology in the management of lupus. The data have been used to influence service development including development of a ‘health passport’ to facilitate communication between family, hospital and school and development of workshops regarding fatigue management and transition.

Background Lupus is a severe, autoimmune disease that is very rare in children and young people. As a regional service and the UK’s only ‘Centre of Excellence for Childhood Lupus’, our patients live across a large geographical area. Many have never met another young person with lupus and report how isolating this could feel. The psychological impact of chronic illnesses are well-known and potentially debilitating. Aims We aimed to develop a series of day-long multidisciplinary workshops for young people with lupus and their families. As part of a stepped-care model of psychological support, we wanted to intervene proactively to promote resilience and coping as well as responding to an individual’s difficulties as they arouse. Method 7 families participated in the first workshop which focused on managing fatigue and research participation. Fatigue was highlighted as a frequent area of concern by young people and their parents when completing a routinely preclinic screening tool. All participants completed a range of standardised psychological measures as well as a workshop feedback form. Results Participant participated in exercises designed to encourage sharing of experiences as well hearing examples of strategies to manage fatigue. High levels of fatigue were identified among lupus patients (mean score on the fatigue severity scale 5.1 (range 4–5.8) where people scoring above 3 points are considered to suffer with fatigue). Young people and their families reported increased confidence in managing fatigue when pre- and post-workshop data were compared. Information about local and national research in paediatric lupus was shared in an interactive session. There was considerable variation in the extent to which young people were coping with lupus. Attendees reported finding the workshop helpful and convenient to attend. Support for siblings, medication, and symptom knowledge were identified as potential future workshop topics. Conclusion The ‘Lupus and You’ workshop allowed young people and their families to share experiences of managing lupus, to develop supportive relationships while also developing resilience and practical strategies for living life fully despite lupus.

This paper begins with a review of the famous "goodness" of electrical machines concept published in 1965 by Laithwaite. Its correctness when applied to induction machines is demonstrated using the metric of torque density, for which we use the word "compactness", measured in Nm/m3. Technical advances in the latter half of the 20th century are discussed, as are properties of axial flux geometry, that have had a significant impact on machine volume. A range of axial flux permanent magnet (PM) machines, some of which are currently in production by Regal Beloit Corporation are presented, studying in particular their compactness. The paper concludes with a discussion of why larger machines can indeed demonstrate an increase in compactness, although much less dramatically than that proposed by Laithwaite, using the air gap shear stress concept. This discussion includes the difference of this relationship for radial and axial flux PM machines.

Vaccine "hesitancy" is an emerging term in the literature and discourse on vaccine decision-making and determinants of vaccine acceptance. It recognizes a continuum between the domains of vaccine acceptance and vaccine refusal and de-polarizes previous characterization of individuals and groups as either anti-vaccine or pro-vaccine. The primary aims of this systematic review are to: 1) identify research on vaccine hesitancy; 2) identify determinants of vaccine hesitancy in different settings including its context-specific causes, its expression and its impact; and 3) inform the development of a model for assessing determinants of vaccine hesitancy in different settings as proposed by the Strategic Advisory Group of Experts Working Group (SAGE WG) for dealing with vaccine hesitancy. A broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy around vaccines, was applied across multiple databases. Peer-reviewed studies were selected for inclusion if they focused on childhood vaccines [≤ 7 years of age], used multivariate analyses, and were published between January 2007 and November 2012. Our results show a variety of factors as being associated with vaccine hesitancy but they do not allow for a complete classification and confirmation of their independent and relative strength of influence. Determinants of vaccine hesitancy are complex and context-specific - varying across time, place and vaccines.

In this paper we describe the scanning electron microscopy techniques of electron backscatter diffraction, electron channeling contrast imaging, wavelength dispersive X-ray spectroscopy, and cathodoluminescence hyperspectral imaging. We present our recent results on the use of these non-destructive techniques to obtain information on the topography, crystal misorientation, defect distributions, composition, doping, and light emission from a range of UV-emitting nitride semiconductor structures. We aim to illustrate the developing capability of each of these techniques for understanding the properties of UV-emitting nitride semiconductors, and the benefits were appropriate, in combining the techniques.

Summary Background The intensity, spread, and effects of public opinion about vaccines are growing as new modes of communication speed up information sharing, contributing to vaccine hesitancy, refusals, and disease outbreaks. We aimed to develop a new application of existing surveillance systems to detect and characterise early signs of vaccine issues. We also aimed to develop a typology of concerns and a way to assess the priority of each concern. Methods Following preliminary research by The Vaccine Confidence Project, media reports (eg, online articles, blogs, government reports) were obtained using the HealthMap automated data collection system, adapted to monitor online reports about vaccines, vaccination programmes, and vaccine-preventable diseases. Any reports that did not meet the inclusion criteria—any reference to a human vaccine or vaccination campaign or programme that was accessible online—were removed from analysis. Reports were manually analysed for content and categorised by concerns, vaccine, disease, location, and source of report, and overall positive or negative sentiment towards vaccines. They were then given a priority level depending on the seriousness of the reported event and time of event occurrence. We used descriptive statistics to analyse the data collected during a period of 1 year, after refinements to the search terms and processes had been made. Findings We analysed data from 10 380 reports (from 144 countries) obtained between May 1, 2011, and April 30, 2012. 7171 (69%) contained positive or neutral content and 3209 (31%) contained negative content. Of the negative reports, 1977 (24%) were associated with impacts on vaccine programmes and disease outbreaks; 1726 (21%) with beliefs, awareness, and perceptions; 1371 (16%) with vaccine safety; and 1336 (16%) with vaccine delivery programmes. We were able to disaggregate the data by country and vaccine type, and monitor evolution of events over time and location in specific regions where vaccine concerns were high. Interpretation Real-time monitoring and analysis of vaccine concerns over time and location could help immunisation programmes to tailor more effective and timely strategies to address specific public concerns. Funding Bill & Melinda Gates Foundation.

An open, paired, randomized, controlled trial of high-dose parenteral ceftazidime (120 mg/[kg.d]) vs. amoxicillin/clavulanate (160 mg/[kg.d]) for the treatment of severe melioidosis was conducted in Ubon Ratchatani in northeastern Thailand. Of 379 patients enrolled in the study, 212 (56%) had culture-proven melioidosis; 106 patients were in each treatment group. The overall mortality rate (47%) was similar for both treatment groups. However, 4 of 75 surviving patients in the ceftazidime group compared with 16 of 69 surviving patients in the amoxicillin/clavulanate group were switched to the alternate regimen because of an unsatisfactory clinical response after > or = 72 hours of treatment (P = .004). The overall therapeutic failure rate (i.e., treatment failure or death due to uncontrolled melioidosis) was significantly higher for the amoxicillin/clavulanate group than for the ceftazidime group (P = .02). Clinical and bacteriologic responses for successfully treated patients were similar in both groups, and both treatments were well tolerated. Parenteral amoxicillin/clavulanate is a safe and effective initial treatment, but parenteral ceftazidime remains the treatment of choice for severe melioidosis.

An open, prospective, randomized, comparative treatment trial was conducted to compare the therapeutic efficacy of high-dose intravenous imipenem and ceftazidime for acute severe melioidosis. Adult Thai patients with suspected acute, severe melioidosis were randomized to receive either imipenem, at a dosage of 50 mg/(kg x d), or ceftazidime, at a dosage of 120 mg/(kg x d), for a minimum of 10 days. The main outcome measures were death or treatment failure. Of the 296 patients enrolled, 214 had culture-confirmed melioidosis, and 132 (61.7%) of them had positive blood cultures. Mortality among patients with melioidosis was 36.9% overall. There were no differences in survival overall (P = .96) or after 48 hours (P = .3). Treatment failure after 48 hours was more common among patients treated with ceftazidime (P = .011). Both treatments were well tolerated. Imipenem is a safe and effective treatment for acute severe melioidosis and may be considered an alternative to ceftazidime.

Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.

The pGALS (paediatric Gait, Arms, Legs, Spine) Musculoskeletal (MSK) screen is validated in English-speaking school-aged children and has been shown to be useful in acute paediatric practice in the UK. The aim of this study is to evaluate the practicality and acceptability of pGALS in children in an acute hospital setting in Malawi. School-aged inpatients and children presenting to the Queen Elizabeth Hospital Blantyre, Malawi, participated. Practicality (time taken, degree of completion) and patient/parent assessed acceptability (time take, discomfort) were assessed using a 'smiley face' visual analogue scale. Fifty-one children (median age 8 years) were assessed; 23 out of 51 (45%) in the emergency department and the remainder were inpatients. Most presentations were infection or trauma related (n = 35, 69%). Practicality of pGALS was good [median time to complete pGALS--4 min (range 1.8-7.4)] and completed in 48 out of 51 children (94%). Acceptability was high; 98% of parents considered the time taken to be acceptable, 84% of children deemed little/no additional discomfort. Abnormalities using pGALS were found in 21 out of 51 (41%), mostly in the lower limbs. The pGALS MSK screen was practical and acceptable in this acute setting. Abnormal findings were common.

International audience; The objective of this work is to advance the understanding of the structure and dynamics of the middle altitude region of the martian atmosphere. While numerous advancements have been made in the level of scientific understanding of Mars's upper and lower atmospheres over the past several decades, insight into the mechanisms of the middle atmosphere has come at a significantly slower pace due to the small number of datasets available for this region. Over the past decade this has begun to change, with renewed interest by NASA and ESA to send spacecraft to Mars. The result of these recent efforts is a growing database for Mars's middle atmosphere, enabling long-awaited and necessary studies characterizing the middle altitude region. Various numerical models of the martian atmosphere can now be validated and constrained using this database. We utilize the Mars Express/Spectroscopy for the Investigation of the Characteristics of the Atmosphere of Mars (MEX/SPICAM) density and temperature datasets to characterize the middle atmosphere as well as validate and constrain the coupled multi-dimensional Mars General Circulation Model-Mars Thermosphere General Circulation Model (MGCM-MTGCM) at middle altitudes in order to explore the underlying physics controlling the structure and dynamics at these levels. The results of this study stress the importance of proper dust prescription within the MGCM-MTGCM for accurately reproducing the density and thermal structure of the middle and upper atmosphere regions on Mars. Simulations conducted with horizontal dust opacities that are consistent with the SPICAM observation period (i.e. Mars Odyssey/THEMIS opacities) yield modeled densities and temperatures that are closer to the observed values than simulations conducted with "typical" dust conditions (i.e. Mars Global Surveyor/TES opacities). We show that the MGCM-MTGCM closely reproduces the observed densities during low-dust and high-dust scenarios but displays difficulty during the pre-dust-season "ramp-up" period (Ls not, vert, similar 120-200°) during MY27. In addition, we show that the MGCM-MTGCM accurately reproduces the temperature profiles below the mesopause, but, the mesopause altitude is too low and its temperature warmer (5-10 K) than observations. This may be related to nightside dynamical heating processes that require further refinement. In addition, CO2 15-μm cooling rates may be too small, which would be consistent with underestimated atomic O abundances.

Background: The aim of this study was to estimate the effect of rheumatoid arthritis (RA) on the personal income of a cohort of individuals with RA in Australia. Methods: A cross-sectional study of a sample of 497 working age people with RA in Adelaide, South Australia was carried out. Results: The average personal income of an individual with RA in our cohort in 2003–2004 was $A22 400 compared with the Australian mean annual income of $A38 000. When standardized, the income of our cohort was 66% that of the average income of the Australian population. Overall one-third of the RA cohort relied principally on the social security system for their income and more than 75% of the cohort estimated they had lost greater than $A10 000 per annum in personal income as a result of their disease. Individuals with RA who were not working had annual incomes on average of more than $A20 000 less than those who continued to work. Conclusion: The personal income loss associated with RA in Australia is of enormous significance. It reduces a large population of individuals to relative financial poverty and potentially limits their access to a range of services including private health services.

The aim of this study was to re-assess whether the use of a ‘one-knife technique’ can be considered as safe as the alternative practice of using separate skin and inside knives for elective orthopaedic surgery. A total of 609 knife blades from 203 elective orthopaedic operations, with equal numbers of skin, inside and control blades, were cultured using direct and enrichment media. We found 31 skin blades (15.3%), 22 inside blades (10.8%), and 13 control blades (6.4%) gave bacterial growth. Of the 31 contaminated skin blades only three (9.7%) had growth of the same organism as found on the corresponding inside blade. It is not known whether contamination of deeper layers in the remaining 90% was prevented by changing the knife after the skin incision. The organisms cultured were predominantly coagulase-negative staphylococci and proprionibacterium species; both are known to be the major culprits in peri-prosthetic infection. Our study suggests that the use of separate skin and inside knives should be maintained as good medical practice, since the cost of a single deep infection in human and financial terms can be considerable.

International audience; The Composite Infrared Spectrometer (CIRS) is a remote-sensing Fourier Transform Spectrometer (FTS) on the Cassini orbiter that measures thermal radiation over two decades in wavenumber, from 10 to 1400 cm- 1 (1 mm to 7mu m), with a spectral resolution that can be set from 0.5 to 15.5 cm- 1. The far infrared portion of the spectrum (10 600 cm- 1) is measured with a polarizing interferometer having thermopile detectors with a common 4-mrad field of view (FOV). The middle infrared portion is measured with a traditional Michelson interferometer having two focal planes (600 1100 cm- 1, 1100 1400 cm- 1). Each focal plane is composed of a 1× 10 array of HgCdTe detectors, each detector having a 0.3-mrad FOV. CIRS observations will provide three-dimensional maps of temperature, gas composition, and aerosols/condensates of the atmospheres of Titan and Saturn with good vertical and horizontal resolution, from deep in their tropospheres to high in their mesospheres. CIRS's ability to observe atmospheres in the limb-viewing mode (in addition to nadir) offers the opportunity to provide accurate and highly resolved vertical profiles of these atmospheric variables. The ability to observe with high-spectral resolution should facilitate the identification of new constituents. CIRS will also map the thermal and compositional properties of the surfaces of Saturn's icy satellites. It will similarly map Saturn's rings, characterizing their dynamical and spatial structure and constraining theories of their formation and evolution. The combination of broad spectral range, programmable spectral resolution, the small detector fields of view, and an orbiting spacecraft platform will allow CIRS to observe the Saturnian system in the thermal infrared at a level of detail not previously achieved.

Background. Public confidence in vaccination is vital to the success of immunisation programmes worldwide. Understanding the dynamics of vaccine confidence is therefore of great importance for global public health. Few published studies permit global comparisons of vaccination sentiments and behaviours against a common metric. This article presents the findings of a multi-country survey of confidence in vaccines and immunisation programmes in Georgia, India, Nigeria, Pakistan, and the United Kingdom (UK) � these being the first results of a larger project to map vaccine confidence globally. Methods. Data were collected from a sample of the general population and from those with children under 5 years old against a core set of confidence questions. All surveys were conducted in the relevant local-language in Georgia, India, Nigeria, Pakistan, and the UK. We examine confidence in immunisation programmes as compared to confidence in other government health services, the relationships between confidence in the system and levels of vaccine hesitancy, reasons for vaccine hesitancy, ultimate vaccination decisions, and their variation based on country contexts and demographic factors. Results. The numbers of respondents by country were: Georgia (n=1000); India (n=1259); Pakistan (n=2609); UK (n=2055); Nigerian households (n=12554); and Nigerian health providers (n=1272). The UK respondents with children under five years of age were more likely to hesitate to vaccinate, compared to other countries. Confidence in immunisation programmes was more closely associated with confidence in the broader health system in the UK (Spearmans �i=0.5990), compared to Nigeria (�i=0.5477), Pakistan (�i=0.4491), and India (�i=0.4240), all of which ranked confidence in immunisation programmes higher than confidence in the broader health system. Georgia had the highest rate of vaccine refusals (6 %) among those who reported initial hesitation. In all other countries surveyed most respondents who reported hesitating to vaccinate went on to receive the vaccine except in Kano state, Nigeria, where the percentage of those who ultimately refused vaccination after initially hesitating was as high as 76%) Reported reasons for hesitancy in all countries were classified under the domains ofconfidence, � �convenience, � orcomplacency, � and confidence issues were found to be the primary driver of hesitancy in all countries surveyed. Abstract Background. Public confidence in vaccination is vital to the success of immunisation programmes worldwide. Understanding the dynamics of vaccine confidence is therefore of great importance for global public health. Few published studies permit global comparisons of vaccination sentiments and behaviours against a common metric. This article presents the findings of a multi-country survey of confidence in vaccines and immunisation programmes in Georgia, India, Nigeria, Pakistan, and the United Kingdom (UK) � these being the first results of a larger project to map vaccine confidence globally. Methods. Data were collected from a sample of the general population and from those with children under 5 years old against a core set of confidence questions. All surveys were conducted in the relevant local-language in Georgia, India, Nigeria, Pakistan, and the UK. We examine confidence in immunisation programmes as compared to confidence in other government health services, the relationships between confidence in the system and levels of vaccine hesitancy, reasons for vaccine hesitancy, ultimate vaccination decisions, and their variation based on country contexts and demographic factors. Results. The numbers of respondents by country were: Georgia (n=1000); India (n=1259); Pakistan (n=2609); UK (n=2055); Nigerian households (n=12554); and Nigerian health providers (n=1272). The UK respondents with children under five years of age were more likely to hesitate to vaccinate, compared to other countries. Confidence in immunisation programmes was more closely associated with confidence in the broader health system in the UK (Spearmans �i=0.5990), compared to Nigeria (�i=0.5477), Pakistan (�i=0.4491), and India (�i=0.4240), all of which ranked confidence in immunisation programmes higher than confidence in the broader health system. Georgia had the highest rate of vaccine refusals (6 %) among those who reported initial hesitation. In all other countries surveyed most respondents who reported hesitating to vaccinate went on to receive the vaccine except in Kano state, Nigeria, where the percentage of those who ultimately refused vaccination after initially hesitating was as high as 76%) Reported reasons for hesitancy in all countries were classified under the domains ofconfidence, � �convenience, � orcomplacency, � and confidence issues were found to be the primary driver of hesitancy in all countries surveyed. Abstract Background. Public confidence in vaccination is vital to the success of immunisation programmes worldwide. Understanding the dynamics of vaccine confidence is therefore of great importance for global public health. Few published studies permit global comparisons of vaccination sentiments and behaviours against a common metric. This article presents the findings of a multi-country survey of confidence in vaccines and immunisation programmes in Georgia, India, Nigeria, Pakistan, and the United Kingdom (UK) � these being the first results of a larger project to map vaccine confidence globally. Methods. Data were collected from a sample of the general population and from those with children under 5 years old against a core set of confidence questions. All surveys were conducted in the relevant local-language in Georgia, India, Nigeria, Pakistan, and the UK. We examine confidence in immunisation programmes as compared to confidence in other government health services, the relationships between confidence in the system and levels of vaccine hesitancy, reasons for vaccine hesitancy, ultimate vaccination decisions, and their variation based on country contexts and demographic factors. Results. The numbers of respondents by country were: Georgia (n=1000); India (n=1259); Pakistan (n=2609); UK (n=2055); Nigerian households (n=12554); and Nigerian health providers (n=1272). The UK respondents with children under five years of age were more likely to hesitate to vaccinate, compared to other countries. Confidence in immunisation programmes was more closely associated with confidence in the broader health system in the UK (Spearmans �i=0.5990), compared to Nigeria (�i=0.5477), Pakistan (�i=0.4491), and India (�i=0.4240), all of which ranked confidence in immunisation programmes higher than confidence in the broader health system. Georgia had the highest rate of vaccine refusals (6 %) among those who reported initial hesitation. In all other countries surveyed most respondents who reported hesitating to vaccinate went on to receive the vaccine except in Kano state, Nigeria, where the percentage of those who ultimately refused vaccination after initially hesitating was as high as 76%) Reported reasons for hesitancy in all countries were classified under the domains ofconfidence, � �convenience, � orcomplacency, � and confidence issues were found to be the primary driver of hesitancy in all countries surveyed.

Delayed diagnosis of jersey finger injuries often results in retraction of the flexor digitorum profundus tendon. Current practice recommends limiting tendon advancement to 1 cm in delayed repairs. The purpose of this study was to investigate the biomechanical consequences of tendon shortening on the force required to form a fist. The flexor digitorum profundus muscle was isolated in ten cadaveric forearms and the force required to form a fist was recorded. Simulated jersey finger injuries to the ring finger were then created and repaired. The forces required to pull the fingertips to the palm after serial tendon advancements were measured. There was a near linear increase in the force required for making a fist with shortening up to 2.5 cm. The force required to make a fist should be taken into account when considering the limit of ‘safe’ tendon shortening in delayed repair of jersey finger injuries.

Despite improvements in hemodialyzers with respect to their clearance of middle and high molecular mass molecules, accumulation of specific solutes in the circulation of dialysis patients continues to be a medical problem. A new membrane material, polyester-polymer alloy (PEPA) which has been developed to have a filtration profile akin to that of the natural kidney, is now being used in hemodialyzers. This study evaluates the performance of a PEPA-based hemodialyzer alongside a selection of available competing high-flux dialyzers using official standardized methods. The new membrane material appears to be a viable alternative which offers performance at least as good as that of the competition. The promising results obtained with the PEPA membrane suggest that a detailed clinical performance study should be undertaken.