How does cognitive behavior therapy for dissociative seizures work? A mediation analysis of the CODES trial.

BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Illness representations of people with later-onset functional seizures.

PURPOSE: Although functional seizures can start at any age, little is known about the individuals for whom onset occurs after the age of 40. It has been proposed that health-related traumatic events are more relevant causal factors for people with 'later-onset functional seizures' than for those whose functional seizures begin earlier in life, however, the illness representations of people with later-onset functional seizures have not yet been investigated. This study aimed to understand the experiences and illness representations of people with later-onset functional seizures. METHODS: This was a mixed-methods study. People with later-onset functional seizures were recruited via a neurologist's caseload and online membership-led organisations. Semi-structured interview transcripts were analysed using Template Analysis according to the Common-Sense Model (CSM). Self-report measures of demographic and clinical details were collected to characterise the sample and verify themes. RESULTS: Eight people with later-onset functional seizures participated in the study. Illness representations relating to all domains of the CSM as well as an additional theme of 'Triggers' were identified. Functional seizures were characterised as a mysterious brain disorder analogous to a computer malfunction and involving involuntary movements associated with alterations in consciousness. Perceptions of duration were indefinite, and triggers were unknown or at the extremes of autonomic arousal. Half of the sample identified health-related events/trauma as causal. Opinions were divided on 'cumulative life stress' as a causal factor. Most perceived themselves to have limited or no control but having 'control' over seizures was conceptualised as different to reducing their likelihood, frequency, or impact. Later-onset functional seizures were viewed as being more detrimental for caring and financial responsibilities but to have advantages for acceptance. CONCLUSIONS: This is the first study to assess the illness representations of people with later-onset functional seizures. Many themes were similar to those identified in samples including people with earlier-onset functional seizures. Health-related trauma or events were the most strongly endorsed perceived causal factor, but with the exception of 'consequences', all representations were characterised by uncertainty. Clinicians should hold in mind the interaction between life stage and the consequences of later-onset functional seizures.

Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

BACKGROUND: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. OBJECTIVES: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. METHODS: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. RESULTS: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. CONCLUSIONS: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.

Online psychological interventions to reduce symptoms of depression, anxiety, and general distress in those with chronic health conditions: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Over the past 15 years, there has been substantial growth in web-based psychological interventions. We summarize evidence regarding the efficacy of web-based self-directed psychological interventions on depressive, anxiety and distress symptoms in people living with a chronic health condition. METHOD: We searched Medline, PsycINFO, CINAHL, EMBASE databases and Cochrane Database from 1990 to 1 May 2019. English language papers of randomized controlled trials (usual care or waitlist control) of web-based psychological interventions with a primary or secondary aim to reduce anxiety, depression or distress in adults with a chronic health condition were eligible. Results were assessed using narrative synthases and random-effects meta-analyses. RESULTS: In total 70 eligible studies across 17 health conditions [most commonly: cancer (k = 20), chronic pain (k = 9), arthritis (k = 6) and multiple sclerosis (k = 5), diabetes (k = 4), fibromyalgia (k = 4)] were identified. Interventions were based on CBT principles in 46 (66%) studies and 42 (60%) included a facilitator. When combining all chronic health conditions, web-based interventions were more efficacious than control conditions in reducing symptoms of depression g = 0.30 (95% CI 0.22-0.39), anxiety g = 0.19 (95% CI 0.12-0.27), and distress g = 0.36 (95% CI 0.23-0.49). CONCLUSION: Evidence regarding effectiveness for specific chronic health conditions was inconsistent. While self-guided online psychological interventions may help to reduce symptoms of anxiety, depression and distress in people with chronic health conditions in general, it is unclear if these interventions are effective for specific health conditions. More high-quality evidence is needed before definite conclusions can be made.

Patients with resolution of low-lying placenta and placenta previa remain at increased risk of postpartum hemorrhage.

OBJECTIVE: To determine whether women who experience resolution of low placentation (low-lying placenta or placenta previa) are at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. METHODS: This was a retrospective cohort study of women who delivered at Mount Sinai Hospital between 2015 and 2019, and who were diagnosed with low-lying placenta or placenta previa on transvaginal ultrasound at the time of the second-trimester anatomical survey, with resolution of low placentation on subsequent ultrasound examination. Women undergoing second-trimester anatomical survey who had normal placentation on transvaginal ultrasound 3 days before or after the cases were randomly identified for comparison. The primary outcome was the rate of postpartum hemorrhage. Secondary outcomes included the need for a blood transfusion, use of additional uterotonic medication, the need for additional procedures to control bleeding, and maternal admission to the intensive care unit. Outcomes were assessed using a multivariable logistic regression model. RESULTS: A total of 1256 women were identified for analysis, of whom 628 had resolved low placentation and 628 had normal placentation. Women with resolved low placentation, compared to those with normal placentation throughout pregnancy, had significantly higher mean age (33.0 ± 5.4 years vs 31.9 ± 5.5 years; P < 0.01) and lower mean body mass index at delivery (27.9 ± 5.5 kg/m2 vs 30.2 ± 5.7 kg/m2 ; P < 0.01), and were more likely to have undergone in-vitro fertilization, be of non-Hispanic white race, have posterior placental location (all P < 0.01) and have private/commercial health insurance (P = 0.04). Patients with resolved low placentation vs normal placentation had greater odds of postpartum hemorrhage (adjusted odds ratio (aOR), 3.5 (95% CI, 2.0-6.0); P < 0.01), use of additional uterotonic medication (aOR, 2.2 (95% CI, 1.5-3.1); P < 0.01) and increased rates of additional procedures to control bleeding (aOR, 4.0 (95% CI, 1.3-11.9); P = 0.01). CONCLUSION: Despite high rates of resolution of low-lying placenta and placenta previa by term, women with resolved low placentation remain at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Reproductive factors and breast arterial calcification: a systematic review and meta-analysis.

BACKGROUND: Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). METHODS: MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. RESULTS: Nineteen observational studies (n = 47,249; three cohort studies, seven case-control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50-4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68-3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40-0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. CONCLUSIONS: BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO: CRD42020141644.

Is contact between men who have sex with men and non-governmental organizations providing harm reduction associated with improved HIV outcomes?

OBJECTIVES: There is a high prevalence of HIV (5.2% in 2018) among men who have sex with men (MSM) in Ukraine. HIV testing, condom provision and facilitated linkage to HIV treatment have been funded by various bodies through non-governmental organizations (NGOs). We investigated whether contact with these NGOs was associated with improved prevention and treatment outcomes among MSM in Ukraine. METHODS: Data were taken from four rounds of integrated bio-behavioural surveys among MSM in Ukraine (2011, N = 5950; 2013, N = 8101; 2015, N = 4550; 2018, N = 5971) including HIV testing combined with questionnaire responses. Data were analysed using mixed-effect regression models, which estimated associations between being an NGO client and behavioural, HIV testing and HIV treatment outcomes, adjusted for demographic factors. RESULTS: Those MSM who were NGO clients were more likely than non-clients to have been HIV tested in the last year [adjusted odds ratio (aOR) = 7.01, 95% confidence interval (CI): 6.45-7.62] or ever (aOR = 11.00, 95% CI: 9.77-12.38), to have used a condom for the last anal sex act (aOR = 1.32, 95% CI: 1.21-1.43), and to have recently either bought or received condoms (aOR = 21.27, 95% CI: 18.01-25.12). HIV-positive MSM were more likely to have contact with NGOs (aOR = 1.61, 95% CI: 1.39-1.86). Among the HIV-positive MSM, those who were NGO clients were more likely to be registered at an AIDS centre (aOR = 2.24, 95% CI: 1.61-3.11) and to be on antiretroviral treatment (aOR = 2.20, 95% CI: 1.51-3.20). CONCLUSIONS: In Ukraine, being in contact with MSM-targeted NGOs is associated with better outcomes for HIV prevention, testing and treatment, suggesting that NGO harm reduction projects for MSM have had a beneficial impact on reducing HIV transmission and morbidity.

Randomized preclinical study of machine perfusion in vascularized composite allografts.

BACKGROUND: Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. METHODS: A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. RESULTS: NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. CONCLUSION: Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

Transient heating in fixed length optical cavities for use as temperature and pressure standards.

Optical refractometry techniques enable realization of both pressure and temperature directly from properties of the gas. The NIST refractometer, a fixed length optical cavity (FLOC) has previously been evaluated for operation as pressure standard, and now in this paper, is evaluated for the feasibility of operation as a primary temperature standard as well. The challenge is that during operation, one cavity is filled with gas. Gas dynamics predicts that this will result in heating which in turn will affect the cavity temperature uniformity, impeding the ability to measure the gas temperature with sufficient accuracy to make the standard useful as a primary standard for temperature or pressure. Temperature uniformity across the refractometer must be less than 0.5 mK for measurements of the refractivity to be sufficiently accurate for the FLOC. This paper compares computer modeling to laboratory measurements, enabling us to validate the model to predict thermal behavior and to accurately determine the measurement uncertainty of the technique. The results presented in this paper show that temperature of the glass elements of the refractometer and 'thermal-shell' copper chamber are equivalent to within 0.5 mK after an equilibration time of 3000 s (when going from 1 kPa to 100 kPa). This finding enables measurements of the copper chamber to determine the gas temperature to within an uncertainty (k = 1) of 0.5 mK. Additionally, the NIST refractometer is evaluated for feasibility of operation as temperature standard.

Opinions and clinical practices related to diagnosing and managing functional (psychogenic) movement disorders: changes in the last decade.

BACKGROUND AND PURPOSE: There is large variability in the diagnostic approach and clinical management in functional movement disorders (FMD). This study aimed to examine whether opinions and clinical practices related to FMD have changed over the past decade. METHODS: Adapted from a 2008 version, we repeated the survey to members of the International Parkinson and Movement Disorder Society (MDS). RESULTS: In all, 864/7689 responses (denominator includes non-neurologists) were received from 92 countries. Respondents were more often male (55%), younger than 45 (65%) and from academic practices (85%). Although the likelihood of ordering neurological investigations prior to delivering a diagnosis of FMD was nearly as high as in 2008 (47% vs. 51%), the percentage of respondents communicating the diagnosis without requesting additional tests increased (27% vs. 19%; P = 0.003), with most envisioning their role as providing a diagnosis and coordinating management (57% vs. 40%; P < 0.001). Compared to patients with other disorders, 64% of respondents were more concerned about missing a diagnosis of another neurological disorder. Avoiding iatrogenic harm (58%) and educating patients about the diagnosis (53%) were again rated as the most effective therapeutic options. Frequent treatment barriers included lack of physician knowledge and training (32%), lack of treatment guidelines (39%), limited availability of referral services (48%) and cultural beliefs about psychological illnesses (50%). The preferred term for communication favored 'functional' over 'psychogenic' (P < 0.001). CONCLUSIONS: Attitudes and management of FMDs have changed over the past decade. Important gaps remain in access to treatment and in the education of neurologists about the inclusionary approach to FMD diagnosis.

Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE).

Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then 1H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P < 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

Abnormal sleep in patients with epileptic or dissociative (non-epileptic) seizures: a polysomnography study.

BACKGROUND AND PURPOSE: The aim of this study was to identify the prevalence of sleep disorders and measure the objective sleep quality in patients with seizure disorders. METHODS: Patients admitted for video electroencephalography monitoring were prospectively recruited and polysomnography was performed on the third night of monitoring. RESULTS: A total of 4/44 (9%) patients with epilepsy and 2/22 (9%) patients with dissociative seizures were found to have mild sleep-disordered breathing. Three (7%) patients with epilepsy were found to have mild or moderate obstructive sleep apnea-hypopnea syndrome (OSAHS) and three (14%) patients with dissociative seizures had mild or moderate OSAHS. Most patients with sleep-disordered breathing or OSAHS were overweight or obese. Time awake after sleep onset was high in both groups. There were no significant differences in sleep architecture between the groups except for a difference in average N3 sleep stage proportion. Periodic limb movements (PLMs) were common in both groups and 27% of patients with dissociative seizures had both high PLM rates and high arousal indices, suggesting a high prevalence of probable PLM disorder in that group (compared with 9% in the epilepsy group). CONCLUSIONS: Our findings contradict the commonly reported high comorbidity of OSAHS and epilepsy, and question its purported clinical relevance. High rates of PLMs were found in patients with dissociative seizures. In both patient groups, high awake after sleep onset times were indicative of sleep disruption, which can have an epileptogenic effect and is known to increase dissociative tendencies.

The Genetic Structure of Populations of the Douglas-Fir Swiss Needle Cast Fungus Nothophaeocryptopus gaeumannii in New Zealand.

Swiss needle cast is a foliar disease of Douglas-fir (Pseudotsuga menziesii) that results in premature foliage loss and reduced growth. The causal fungus, Nothophaeocryptopus gaeumannii, was first detected in New Zealand in 1959 and spread throughout the North and South Islands over the following decades. The contemporary genetic structure of the N. gaeumannii population in New Zealand was assessed by analyzing 468 multilocus SSR genotypes (MLGs) from 2,085 N. gaeumannii isolates collected from 32 sites in the North and South Islands. Overall diversity was lower than that reported from native N. gaeumannii populations in the northwestern United States, which was expected given that N. gaeumannii is introduced in New Zealand. Linkage disequilibrium was significantly higher than expected under random mating, suggesting that population structure is clonal. Populations of N. gaeumannii in the North and South Islands were weakly differentiated, and the isolates collected from sites within the islands were moderately differentiated. This suggests that gene flow has occurred between the N. gaeumannii populations in the North and South Islands, and between the local N. gaeumannii populations within each island. Eighteen isolates of N. gaeumannii Lineage 2, which has previously been reported only from western Oregon, were recovered from two sites in the North Island and four sites in the South Island. The most likely explanation for the contemporary distribution of N. gaeumannii in New Zealand is that it was introduced on infected live seedlings through the forestry or ornamental nursery trade, as the fungus is neither seed borne nor saprobic, and the observed population structure is not consistent with a stochastic intercontinental dispersal event.

High-resolution air-clad imaging fibers.

We present a coherent fiber bundle comprising over 11,000 doped silica cores separated by an air-filled cladding. The fiber is characterized, and its imaging quality is shown to be a substantial improvement over the commercial state of the art, with comparable resolution over an unparalleled spectral range.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Pollination context alters female advantage in gynodioecious Silene vulgaris.

Gynodioecy, the co-occurrence of females and hermaphrodites, is arguably the most common angiosperm gender polymorphism in many florae. Females' ability to invade and persist among hermaphrodites depends, in part, on pollinators providing adequate pollination to females. We directly measured diurnal and nocturnal pollinators' contributions to female and hermaphrodite seed production in artificial populations of gynodioecious Silene vulgaris by experimentally restricting pollinator access. We found that female relative seed production in this system depended strongly on pollination context: females produced more than twice as many seeds as hermaphrodites in the context of abundant, nectar-collecting moths. Conversely, females showed no seed production advantage in the context of pollen-collecting syrphid flies and bees due to acutely hermaphrodite-biased visitation. We infer that variation in pollinator type, behaviour and abundance may be important for achieving the female relative fitness thresholds necessary for the maintenance of gynodioecy. Generally, our study illustrates how pollinator-mediated mechanisms may influence the evolution of breeding systems and associated suites of floral traits. Segments of a pollinator community may facilitate gynodioecy by selecting for plant characteristics that increase the attractiveness of both sexes to pollinators, such as nectar rewards. Conversely, discriminating visitors in search of pollen may restrict gynodioecy in associated plant lineages by reducing male steriles' fitness below threshold levels.

Role of breast density measurement in screening for breast cancer.

Mammographic breast density is an established risk factor for breast cancer and significantly reduces the sensitivity of mammography, yet its use within breast cancer screening programs in Australia is limited. We provide a contemporary snapshot of the role of breast density measurement in screening for breast cancer and review the recent evidence for an increasing role of breast density measurement as: a predictor of breast cancer risk, a predictor of 'masking', and a biomarker to monitor effectiveness of intervention strategies for primary prevention or improved breast cancer outcomes.

Towards Photonic based Pascal Realization as a Primary Pressure Standard.

New techniques using refractometry have enabled gas pressure to be measured using laser interferometry. Two key techniques have been studied at NIST which include the Fixed Length Optical Cavity (FLOC) and the Variable Length Optical Cavity (VLOC). The measurement techniques are described and the traceability of these measurements through quantum mechanics that enables them to be primary standards. This technology is critical for gas pressure metrology to move away from artifact based standards (and especially mercury based) and move to quantum based methods for realization of the pascal.

Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) appear to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). However, ANCA alone are not sufficient to generate disease, and some evidence suggests that infectious triggers may serve as inciting events for AAV disease activity. Antibodies of the immunoglobulin (Ig)M isotype often serve as markers of recent infection, and IgM ANCA have been identified previously in patients with AAV, although the frequency and clinical relevance of IgM ANCA is not well established. We sought to characterize IgM ANCA more clearly by creating a novel enzyme-linked immunosorbent assay (ELISA) for IgM antibodies to proteinase 3 [IgM proteinase 3 (PR3)-ANCA], which we applied to two large, clinically well-characterized trial cohorts of patients with granulomatosis with polyangiitis and microscopic polyangiitis. In the first cohort, IgM PR3-ANCA occurred with a frequency of 15·0%, and were associated with a higher degree of disease severity and a trend towards a higher rate of alveolar haemorrhage (29·6 versus 15·7%, P = 0·10). Analysis of follow-up samples in this cohort showed that the presence of IgM PR3-ANCA was transient, but could recur. In the second cohort, IgM PR3-ANCA occurred with a frequency of 41·1%, and were also associated with a higher degree of disease severity. A higher rate of alveolar haemorrhage was observed among those with IgM PR3-ANCA (45·3 versus 15·8%; P < 0·001). The association of transient IgM PR3-ANCA with an acute respiratory manifestation of AAV suggests a possible link between an infectious trigger and AAV disease activity.