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Satire is a form of expression which tackles complex, contemporary issues in a nuanced, jesting spirit. Vitally, it does so through humour and provocation. This article demonstrates why we should not place extensive limits on controversial satire. At the European Court level, this requires a robust proportionality assessment of each satirical expression, rather than granting a wide margin of appreciation to national authorities which are more likely to uphold restrictions. The definition of satire in Vereinigung Bildender Künstler (VBK) v Austria did not go far enough to ensure that satire is treated as a distinct category worthy of higher protection at the European Court level. Moreover, the European Court’s worrying approach to controversial expression allows offence to feelings to justify restrictions, thus satire rests in a precarious position. This article remedies this deficiency by elucidating clearer reasoning for protecting satire than that offered in VBK, while providing a rigorous framework for assessing the proportionality of restrictions on satire, in order to provide limited, well-reasoned exceptions.

PURPOSE OF REVIEW To examine respiratory and skin diseases that occur among workers exposed to metalworking fluids (MWFs) used during machining processes. RECENT FINDINGS Five cases of a severe and previously unrecognized lung disease characterized by B-cell bronchiolitis and alveolar ductitis with emphysema (BADE) were identified among workers at a machining facility that used MWFs, although MWF exposure could not be confirmed as the etiology. In the United Kingdom, MWF is now the predominant cause of occupational hypersensitivity pneumonitis (HP). Under continuous conditions associated with respiratory disease outbreaks, over a working lifetime of 45 years, workers exposed to MWF at 0.1 mg/m3 are estimated to have a 45.3% risk of acquiring HP or occupational asthma under outbreak conditions and a 3.0% risk assuming outbreak conditions exist in 5% of MWF environments. In addition to respiratory outcomes, skin diseases such as allergic and irritant contact dermatitis persist as frequent causes of occupational disease following MWF exposure. SUMMARY Healthcare providers need to consider MWF exposure as a potential cause for work-related respiratory and skin diseases. Additional work is necessary to more definitively characterize any potential association between MWF exposures and BADE. Medical surveillance should be implemented for workers regularly exposed to MWF.

We performed a study of tumor necrosis factor inhibitors (TNFi) compared to non-TNFi biologic therapies in rheumatoid arthritis to test whether body mass index (BMI) modified the effect of each therapy.We utilized data from CorEvitas. We studied 3 clinical outcomes based on the Clinical Disease Activity Index (CDAI) at 6 months from therapy initiation: 1) achievement of low disease activity (LDA); 2) a change as large as the minimum clinically important difference (MCID); and 3) the absolute change. We categorized BMI and utilized restricted cubic splines to consider nonlinear associations. We used linear and logistic regression to evaluate associations with response, adjusting for confounders. To determine if comparative effectiveness of therapy varied by BMI, we tested for interactions between BMI and class of therapy.The sample included 2,891 TNFi and 3,010 non-TNFi initiators. Among all initiators, those with severe obesity experienced lower odds of achieving LDA or MCID and less improvement in CDAI score, although associations were attenuated with adjustment. Low BMI was associated with reduced response rates in adjusted models including lower odds of LDA (odds ratio 0.32 [95% confidence interval (95% CI) 0.15, 0.71], P = 0.005). Analyses stratified by TNFi and non-TNFi therapies demonstrated no differences in clinical response rates for TNFi versus non-TNFi across BMI categories (all P for interaction0.05). Estimates for non-TNFi biologics fit within the 95% CI for TNFi.This study observed lower response rates among obese and underweight patients and no evidence of a superior effect of non-TNFi therapy over TNFi therapy in particular BMI categories.

Objectives Numerous states within the USA have legalized cannabis for medical or non-medical (adult/recreational) use. With the increased availability and use of cannabis, occupational and environmental exposures to secondhand cannabis smoke (SHCS) raise concerns over whether non-users may be at risk for a ‘contact high’, impaired neurocognitive function, harm from irritants and carcinogens in smoke, or potentially failing a cannabis screening test. The extent of health effects from potential occupational exposure to SHCS is unknown. This is a study of occupational exposures to SHCS among law enforcement officers (LEOs) providing security at outdoor concerts on a college campus in a state where adult use of cannabis is legal. Methods Investigators evaluated a convenience sample of LEOs’ potential exposure to SHCS and symptoms experienced while providing security during two open-air stadium rock-n-roll concerts on consecutive days in July 2018. During each event, full-shift area and LEO personal air samples were collected for Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of cannabis. Urine (pre- and postevent; n = 58) and blood (postevent; n = 29) were also collected and analyzed for Δ9-THC and two of its metabolites [11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and 11-nor-hydroxy-delta-9-tetrahydrocannabinol (OH-THC)]. Urine samples were analyzed using ultrahigh performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry and results were compared with the Department of Transportation guidelines for urine screening for cannabis. Blood (postevent) samples were also collected and the plasma fraction was tested for Δ9-THC, THC-COOH, and OH-THC using high-performance liquid chromatography coupled with mass spectrometry. LEOs also completed a medical questionnaire asking about symptoms experienced during the concerts. Results Twenty-nine LEOs participated in the evaluation. Measurable amounts of Δ9-THC were found in area (concentrations ranged from non-detectable to 330 ng m−3) and personal air samples (53–480 ng m−3). Small amounts ( Conclusions Identification of Δ9-THC in the breathing zone for some LEOs indicates the potential for airborne exposure to the psychoactive component of cannabis. However, the magnitude of these exposures was small compared with those that would result in a dose of Δ9-THC associated with psychotropic effects. Similarly, THC-COOH was found in the postevent urine of some LEOs at concentrations that were orders of magnitude below active use cut-points used during a cannabis screening test (50 ng ml−1). Exposure to SHCS was not high enough to detect concentrations of THC, THC-COOH, to OH-THC in the blood, which could be due to differences between the limits of detection for the tests employed. The ocular and respiratory symptoms reported by LEOs may be related to irritants in SHCS. However, the health effects of SHCS remain unclear, and further research concerning occupational and environmental exposures is warranted.

Since 2004, the National Institute for Occupational Safety and Health (NIOSH) has received 10 cannabis-related health hazard evaluation (HHE) investigation requests from law enforcement agencies (n = 5), state-approved cannabis grow operations (n = 4), and a coroner’s office (n = 1). Earlier requests concerned potential illicit drug exposures (including cannabis) during law enforcement activities and criminal investigations. Most recently HHE requests have involved state-approved grow operations with potential occupational exposures during commercial cannabis production for medicinal and non-medical (recreational) use. As of 2019, the United States Drug Enforcement Administration has banned cannabis as a Schedule I substance on the federal level. However, cannabis legalization at the state level has become more common in the USA. In two completed cannabis grow operation HHE investigations (two investigations are still ongoing as of 2019), potential dermal exposures were evaluated using two distinct surface wipe sample analytical methods. The first analyzed for delta-9-tetrahydrocannabinol (Δ9-THC) using a liquid chromatography and tandem mass spectrometry (LC–MS–MS) method with a limit of detection (LOD) of 4 nanograms (ng) per sample. A second method utilized high performance liquid chromatography with diode-array detection to analyze for four phytocannabinoids (Δ9-THC, Δ9-THC acid, cannabidiol, and cannabinol) with a LOD (2000 ng per sample) which, when comparing Δ9-THC limits, was orders of magnitude higher than the LC–MS–MS method. Surface wipe sampling results for both methods illustrated widespread contamination of all phytocannabinoids throughout the tested occupational environments, highlighting the need to consider THC form (Δ9-THC or Δ9-THC acid) as well as other biologically active phytocannabinoids in exposure assessments. In addition to potential cannabis-related dermal exposures, ergonomic stressors, and psychosocial issues, the studies found employees in cultivation, harvesting, and processing facilities could potentially be exposed to allergens and respiratory hazards through inhalation of organic dusts (including fungus, bacteria, and endotoxin) and volatile organic compounds (VOCs) such as diacetyl and 2,3-pentanedione. These hazards were most evident during the decarboxylation and grinding of dried cannabis material, where elevated job-specific concentrations of VOCs and endotoxin were generated. Additionally, utilization of contemporary gene sequencing methods in NIOSH HHEs provided a more comprehensive characterization of microbial communities sourced during cannabis cultivation and processing. Internal Transcribed Spacer region sequencing revealed over 200 fungal operational taxonomic units and breathing zone air samples were predominantly composed of Botrytis cinerea, a cannabis plant pathogen. B. cinerea, commonly known as gray mold within the industry, has been previously associated with hypersensitivity pneumonitis. This work elucidates new occupational hazards related to cannabis production and the evolving occupational safety and health landscape of an emerging industry, provides a summary of cannabis-related HHEs, and discusses critical lessons learned from these previous HHEs.

We examined the types of patient monitor alarms encountered in the trauma resuscitation unit of a major level 1 trauma center. Over a 1-year period, 316688 alarms were recorded for 6701 trauma patients (47 alarms/patient). Alarms were more frequent among patients with a Glasgow Coma Scale of 8 or less. Only 2.4% of all alarms were classified as "patient crisis," with the rest in the presumably less critical categories "patient advisory," "patient warning," and "system warning." Nearly half of alarms were ≤5 seconds in duration. In this patient population, a 2-second delay would reduce alarms by 25%, and a delay of 5 seconds would reduce all alarms by 49%.

ObjectiveTo examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA).MethodsThe study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death.ResultsThere were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74).ConclusionTNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.

Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries.We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations. To address confounding, we identified risk predictors for outcomes of interest (mortality, cardiovascular disease, infection, and malignancy). We used patient-level analyses at each registry and central analysis of standardized group-level data.Despite data differences, the coordinated approach enabled consistent variable definitions for key baseline characteristics and outcomes. Selection of restricted subcohorts (e.g., using active joint count criteria) improved baseline comparability with trial patients for some rheumatoid arthritis disease activity measures, but less for other characteristics (e.g., age and comorbidity); however, such selection decreased sample size considerably. For most outcomes, age was the most important risk predictor, emphasizing the importance of age/sex standardization to address confounding. The prospective approach enabled use of recent relevant data; the distributed analysis safeguarded confidentiality of registry data.Compared with reliance on published data alone, a forward-looking coordinated approach across multiple observational data sources can improve comparability and consistency and better support sensitivity analyses and data interpretation, in contextualizing safety data from clinical trials. This approach may have utility to support safety assessments across diverse diseases and drug development programs and satisfy future regulatory requirements.

Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries.Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared. Patients ages18 years with RA, and present in or recruited to the registry from January 1, 2000, were included in the main cohort. Patients from the main cohort with positive rheumatoid factor and/or erosive RA who had received ≥1 synthetic disease-modifying antirheumatic drug (DMARD), and switched to or added another DMARD, were included in the subcohort at time of treatment switch.Age and sex distributions were fairly similar across the registries. The percentage of patients with a high Disease Activity Score in 28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7% NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and CORRONA International including more prevalent cases of RA; the differences were smaller for the subcohort. Prevalence of comorbidities varied across registries (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly due to the way comorbidity data were captured and general cultural differences; the pattern was similar for the subcohorts.Despite different inclusion criteria for the individual RA registries, it is possible to improve the comparability and interpretability of differences across RA registries by applying well-defined cohort definitions.

To identify the rheumatoid arthritis (RA) characteristics associated with increased herpes zoster (HZ) risk in the Corrona registry RA patients, and to evaluate the risk in initiators of tumor necrosis factor inhibitors (TNFi) or non-TNFi biologic agents or (among those who were currently on or had been previously treated with methotrexate [MTX]) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) other than MTX.Cox regression modeling estimated the association between first HZ incidence and selected RA characteristics, including disease activity. Medication-related risk for HZ in RA patients taking current or past MTX (to exclude milder RA disease) were categorized by treatment initiation (TNFi versus non-TNFi versus csDMARD). Hazard ratios (HRs) estimated HZ risk of each treatment initiation category after stratification on trimmed propensity score (PS) quintiles to control for potential confounders.A total of 28,852 patients contributed 95,287 person-years. Seven hundred twenty-nine observed HZ cases yielded a 7.7 (95% confidence interval [95% CI] 7.1-8.2) per 1,000 patient-years crude incidence rate, lower than found in prior RA cohorts. However, consistent with prior studies, increasing age (HR 1.14, 95% CI 1.09-1.19 per 5 years) and prednisone therapy ≥7.5 mg/day (HR 1.81, 95% CI 1.23-2.67) were associated with a higher HZ risk. Referent to TNFi exposure, PS-stratified analysis showed an HR for csDMARDs of 1.36 (95% CI 0.82-2.25) and for non-TNFi of 0.83 (95% CI 0.51-1.38).In the Corrona registry, the HZ risk in RA patients taking prior or current MTX increased with older age and higher prednisone dose. The HZ risk among these patients with RA was comparable after initiation of TNFi versus non-TNFi versus csDMARDs.

Over three hundred years after Leeuwenhoek first applied a microscope to the study of life, new developments in optical systems technology and applications to science continue to emerge on a regular basis. However, most new instrumentation is developed behind closed doors, in the laboratories of optical physicists who collaborate with a small number of scientists to prove out and evaluate the potential impact. Most scientists, including those who stand to benefit the most from the innovations, must wait until the instruments become commercially available before they can evaluate and utilize the latest imaging approaches in their research. The Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute (HHMI) are collaborating to change that situation with the development of an Advanced Imaging Center (AIC) at HHMI's Janelia Research Campus (Janelia) in Northern Virginia. The AIC will provide access to pre-commercial imaging systems developed in the laboratories at Janelia, free of charge to researchers who submit compelling proposals for their use. The AIC will open in the second quarter of 2014, and will initially provide access to five novel imaging systems. The poster will describe the planned organization, proposal review process, initial technology set, and metrics for evaluating the utility of the facility. This new model of inter-institution collaboration and focus on getting important technology into the hands of motivated scientists promises to benefit both instrument developers and a wide range of users.

The experimental nuclear structure data for 199 Pb have been compiled and evaluated. Extensive revisions to the adopted levels, gammas and high--spin data sets for this nuclide have been made based on the new high--spin studies of 1999Po13, 1997Cl03, 1995Ne09, 1994Ba43 (also 1997Hu12,1997Fa15,1997Di03), and 1989Su12. The decay data sets and (α,3nγ) dataset have been revised but no new references are added. The Q values are now adopted from 1995Au04. This revision supersedes earlier 199 Pb data contained in the A=199 update by 1994Ar13 (A. Artna--Cohen, Nuclear Data Sheets 72, 297 (1994)), with literature coverage up to May 25, 1994.

Quality of life (QOL) surveys are increasingly recognized as part of state-of-the-art asthma assessment. Disease-specific surveys quantitate total QOL and subscale domains which, along with changes in these measures, suggest asthma severity and effects of intervention.This study was conducted to (1) compare regional variation in QOL and change in QOL in an allergy practice in the South and (2) to examine if one or a set of questions relating to asthma severity could estimate QOL thereby obviating the need for a complete survey.Fifty-eight patients were administered an asthma specific quality of life (AQOL) questionnaire, the Marks et al Asthma Quality of Life survey, at baseline and surveyed in follow-up at 1 and 6 months. Additional questions were asked concerning bronchodilator use in a day and 1 week, missed work/school days, nocturnal wakening in 1 week due to asthma, emergency room visits in the previous month, and past hospitalizations in the last year. Spirometry was performed at each visit.Baseline AQOL is significantly (P.05) related individually to nocturnal wakening, bronchodilator use in a day, work or school days missed, and hospitalization during the past year. A model combining these factors explains 49% of the variance, r2 = .49. The AQOL score between baseline and the first month shows a significant improvement (P.0001) and this improvement is related (P = .002) to the reduction in nocturnal wakenings during that same time period.Specialty care intervention affected QOL similarly in the Southern practice compared with other regions/countries. Nocturnal wakening, bronchodilator use in a day, workdays missed, and hospitalization in the past year were all significantly correlated with AQOL. Number of nocturnal wakenings and bronchodilator use in a day may not only stratify asthma severity, they roughly stratify AQOL. The wide scatter of AQOL scores for a given indicator of asthma severity makes a limited combination of questions an indicator but not yet a reliable predictor of AQOL.

To compare the incidence rates of malignancy among patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry.We analyzed 2,970 patients with PsA (7,133 patient-years of followup) and 19,260 patients with RA (53,864 patient-years of followup). Using a standardized adjudication process, we identified 40 confirmed malignancies in the patients with PsA and 307 confirmed malignancies in those with RA. Incidence rates were calculated per 100 patient-years. Incidence rate ratios were estimated, with adjustment for age, sex, disease duration, body mass index, disease activity, year of enrollment, and medication use.The overall malignancy incidence per 100 patient-years was similar between patients with PsA and patients with RA (0.56 [95% confidence interval (95% CI) 0.40-0.76] and 0.56 [95% CI 0.50-0.63], respectively). Nonmelanoma skin cancer was the most common type of cancer in the overall cohort, with an incidence rate of 0.21 (95% CI 0.12-0.35) in PsA, and 0.20 (95% CI 0.17-0.24) in RA, with a calculated incidence rate ratio of 1.05 (95% CI 0.61-1.80; P = 0.85). Lymphoma rates were similar in PsA and RA (0.04 [95% CI 0.01-0.12] and 0.04 [95% CI 0.02-0.06], respectively; incidence rate ratio 1.00 [95% CI 0.17-3.11]; P = 0.67). The adjusted incidence rate ratio of malignancy in PsA versus RA was 1.17 (95% CI 0.82-1.69; P = 0.37).The incidence rates across malignancy subtypes were similar in the PsA and RA cohorts from a US registry.

In a prospective double-blind trial, the reactogenicity and immunogenicity of recombinant baculovirus influenza A vaccines containing purified full-length hemagglutinin (HA) were compared with standard trivalent inactivated vaccine (TIV). The recombinant baculovirus influenza A vaccines (rHA0) were monovalent (containing 45 micrograms of A/Beijing/92[H3] and 15, 45, and 135 micrograms of A/Texas/91[H1]) and bivalent (containing 45 micrograms of both A/Beijing/92 and A/Texas/91). The bivalent rHA0 vaccine produced fewer local side effects than the TIV (50% vs. 88%, P = .003). The hemagglutinin inhibition (HAI) responses (defined as a > or = 4 increase in HAI) to A/Beijing rHA0 in the monovalent A/Beijing/92, the bivalent vaccine, and the TIV were 68%, 76%, and 46%, respectively (P = .086). Increasing doses of A/Texas rHA0 (15 micrograms [60%], 45 micrograms [69%], and 135 micrograms [76%]) and bivalent HA (76%) gave better immunologic responses to H1 than did TIV (31%; P = .003).