Costs of switching to low global warming potential inhalers. An economic and carbon footprint analysis of NHS prescription data in England.

OBJECTIVES: Metered-dose inhalers (MDIs) contain propellants which are potent greenhouse gases. Many agencies propose a switch to alternative, low global warming potential (GWP) inhalers, such as dry powder inhalers (DPIs). We aimed to analyse the impact on greenhouse gas emissions and drug costs of making this switch. SETTING: We studied National Health Service prescription data from England in 2017 and collated carbon footprint data on inhalers commonly used in England. DESIGN: Inhalers were separated into different categories according to their mechanisms of action (eg, short-acting beta-agonist). Within each category we identified low and high GWP inhalers and calculated the cost and carbon impact of changing to low GWP inhalers. We modelled scenarios for swapping proportionally according to the current market share of each equivalent DPI (model 1) and switching to the lowest cost pharmaceutically equivalent DPI (model 2). We also reviewed available data on the carbon footprint of inhalers from scientific publications, independently certified reports and patents to provide more accurate carbon footprint information on different types of inhalers. RESULTS: If MDIs using HFA propellant are replaced with the cheapest equivalent DPI, then for every 10% of MDIs changed to DPIs, drug costs decrease by £8.2M annually. However if the brands of DPIs stay the same as 2017 prescribing patterns, for every 10% of MDIs changed to DPIs, drug costs increase by £12.7M annually. Most potential savings are due to less expensive long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) inhalers. Some reliever inhalers (eg, Ventolin) have a carbon footprint over 25 kg CO2e per inhaler, while others use far less 1,1,1,2-tetrafluoroethane (HFA134a) (eg, Salamol) with a carbon footprint of <10 kg CO2e per inhaler. 1,1,1,2,3,3,3-Heptafluoropropane (HFA227ea) LABA/ICS inhalers (eg, Flutiform) have a carbon footprint over 36 kg CO2e, compared with an equivalent HFA134a combination inhaler (eg, Fostair) at <20 kg CO2e. For every 10% of MDIs changed to DPIs, 58 kt CO2e could be saved annually in England. CONCLUSIONS: Switching to DPIs would result in large carbon savings and can be achieved alongside reduced drug costs by using less expensive brands. Substantial carbon savings can be made by using small volume HFA134a MDIs, in preference to large volume HFA134a MDIs, or those containing HFA227ea as a propellant.This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors

Unsteady effects during resistance tests on a ship model in a towing tank

It is known that there are oscillations in the wave resistance during the constantvelocity phase of a towing-tank resistance test on a ship model. In this work, the unsteady thin-ship resistance theory has been applied to this case. The results have been compared with experiment data obtained using a towing carriage the velocity history of which can be programmed. It is demonstrated here that generally excellent correlation exists between the theory and the experiments. In particular, one can predict the influence of Froude number, rate of acceleration, and type of smoothing of the acceleration on the characteristics of the oscillations. These characteristics include the amplitude, rate of decay, frequency, and phasing of the oscillations in the curve of wave resistance versus time

Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls

The central nervous system and the immune system are closely related. Psychiatric illness is often associated with a dysregulation of the immune response. In an attempt to expand on previously reported immune abnormalities in patients with depressive illness, we compared several immune measures in a group of hospitalized depressed patients and healthy normal controls. Depressed patients had significantly higher percentages of circulating neutrophils, significantly lower percentages of circulating lymphocytes and significantly lower in vitro lymphocyte responses to mitogenic stimulation than normal controls. Basal plasma cortisol and circulating levels of the complement components C3 and C4 were also higher in the depressed group. We also found a significant association between cortisol values and the traffic of leukocytes on the one hand, and complement levels and the lymphocyte mitogenic activities on the other. These findings expand previously reported evidence of immune abnormalities in depressive illness and provide a partial explanation for some of these findings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65846/1/j.1600-0447.1989.tb01316.x.pd

Mathematically Gifted Adolescents Have Deficiencies in Social Valuation and Mentalization

Many mathematically gifted adolescents are characterized as being indolent, underachieving and unsuccessful despite their high cognitive ability. This is often due to difficulties with social and emotional development. However, research on social and emotional interactions in gifted adolescents has been limited. The purpose of this study was to observe differences in complex social strategic behaviors between gifted and average adolescents of the same age using the repeated Ultimatum Game. Twenty-two gifted adolescents and 24 average adolescents participated in the Ultimatum Game. Two adolescents participate in the game, one as a proposer and the other as a responder. Because of its simplicity, the Ultimatum Game is an apt tool for investigating complex human emotional and cognitive decision-making in an empirical setting. We observed strategic but socially impaired offers from gifted proposers and lower acceptance rates from gifted responders, resulting in lower total earnings in the Ultimatum Game. Thus, our results indicate that mathematically gifted adolescents have deficiencies in social valuation and mentalization

Mid-term results of the Latitude primary total elbow arthroplasty

Background: The Latitude total elbow prosthesis is a third-generation implant, developed to restore the natural anatomy of the elbow. Literature on this prosthesis is scarce. The aim of this study was to analyze the mid-term results of the Latitude total elbow prosthesis. Methods: We retrospectively evaluated 62 patients (21 men and 41 women). The mean age at the time of surgery was 65 years (range, 28-87 years). The main indication for surgery was inflammatory arthritis. The outcome measures were complications, reoperations, self-reported physical functioning, pain, satisfaction, objectively measured physical functioning, and radiologic signs of loosening. Kaplan-Meier survival analysis was used to determine survival with revision as the endpoint. Results: Sixty-nine primary Latitude prostheses were placed in 62 patients between 2008 and 2019. Six patients (7 prostheses) died, 3 elbows underwent revision, and 9 patients were lost to follow-up. A total of 44 patients (50 prostheses) were available for follow-up. The mean length of follow-up was 51 months (range, 10-144 months). Kaplan-Meier survival analysis showed a survival rate of 82% at 10 years after surgery. The main reason for revision was aseptic loosening. Radial head dissociation was seen in 8 patients (24%), but none had complaints. Self-reported and objectively measured physical functioning yielded good results, although 23 patients (46%) did show radiolucent lines on radiographs. Conclusion: Latitude total elbow arthroplasty is considered a successful procedure with low pain scores, high patient satisfaction, and good physical functioning. Survival rates nonetheless remain low and complication rates remain high yet are comparable to those of other elbow arthroplasties. We recommend biomechanical studies to concentrate on specific postoperative loading instructions to minimize wear and consequent loosening

DNA-based Self-Assembly of Chiral Plasmonic Nanostructures with Tailored Optical Response

Surface plasmon resonances generated in metallic nanostructures can be utilized to tailor electromagnetic fields. The precise spatial arrangement of such structures can result in surprising optical properties that are not found in any naturally occurring material. Here, the designed activity emerges from collective effects of singular components equipped with limited individual functionality. Top-down fabrication of plasmonic materials with a predesigned optical response in the visible range by conventional lithographic methods has remained challenging due to their limited resolution, the complexity of scaling, and the difficulty to extend these techniques to three-dimensional architectures. Molecular self-assembly provides an alternative route to create such materials which is not bound by the above limitations. We demonstrate how the DNA origami method can be used to produce plasmonic materials with a tailored optical response at visible wavelengths. Harnessing the assembly power of 3D DNA origami, we arranged metal nanoparticles with a spatial accuracy of 2 nm into nanoscale helices. The helical structures assemble in solution in a massively parallel fashion and with near quantitative yields. As a designed optical response, we generated giant circular dichroism and optical rotary dispersion in the visible range that originates from the collective plasmon-plasmon interactions within the nanohelices. We also show that the optical response can be tuned through the visible spectrum by changing the composition of the metal nanoparticles. The observed effects are independent of the direction of the incident light and can be switched by design between left- and right-handed orientation. Our work demonstrates the production of complex bulk materials from precisely designed nanoscopic assemblies and highlights the potential of DNA self-assembly for the fabrication of plasmonic nanostructures.Comment: 5 pages, 4 figure

Tunable magnetic exchange interactions in manganese-doped inverted core/shell ZnSe/CdSe nanocrystals

Magnetic doping of semiconductor nanostructures is actively pursued for applications in magnetic memory and spin-based electronics. Central to these efforts is a drive to control the interaction strength between carriers (electrons and holes) and the embedded magnetic atoms. In this respect, colloidal nanocrystal heterostructures provide great flexibility via growth-controlled `engineering' of electron and hole wavefunctions within individual nanocrystals. Here we demonstrate a widely tunable magnetic sp-d exchange interaction between electron-hole excitations (excitons) and paramagnetic manganese ions using `inverted' core-shell nanocrystals composed of Mn-doped ZnSe cores overcoated with undoped shells of narrower-gap CdSe. Magnetic circular dichroism studies reveal giant Zeeman spin splittings of the band-edge exciton that, surprisingly, are tunable in both magnitude and sign. Effective exciton g-factors are controllably tuned from -200 to +30 solely by increasing the CdSe shell thickness, demonstrating that strong quantum confinement and wavefunction engineering in heterostructured nanocrystal materials can be utilized to manipulate carrier-Mn wavefunction overlap and the sp-d exchange parameters themselves.Comment: To appear in Nature Materials; 18 pages, 4 figures + Supp. Inf

Elbow Joint Loads during Simulated Activities of Daily Living:Implications for Formulating Recommendations after Total Elbow Arthroplasty.

Background: Overloading of the elbow joint prosthesis following total elbow arthroplasty can lead to implant failure. Joint moments during daily activities are not well-contextualized for a prosthesis' failure limits and the effect of the current postoperative instruction on elbow joint loading is unclear. This study investigates the difference in elbow joint moments between simulated daily tasks and between flexion-extension, pronation-supination, varus-valgus movement directions. Additionally, the effect of the current postoperative instruction on elbow joint load is examined.Methods: Nine healthy participants (age 45.8 ± 17 years, 3 males) performed eight tasks; driving a car, opening a door, rising from chair, lifting, sliding, combing hair, drinking, emptying cup, without and with the instruction "not lifting more than 1 kg". Upper limb kinematics and hand contact forces were measured. Elbow joint angles and net moments were analyzed using inverse dynamic analysis, where the net moments are estimated from movement data and external forces.Results: Peak elbow joint moments differed significantly between tasks (p &lt; 0.01) and movement directions (p &lt; 0.01). The most and least demanding tasks were, rising from a chair (13.4 Nm extension, 5.0 Nm supination, 15.2 Nm valgus) and sliding (4.3 Nm flexion, 1.7 Nm supination, 2.6 Nm varus). Net moments were significantly reduced after instruction only in the chair task (p &lt; 0.01).Conclusion: This study analyzed elbow joint moments in different directions during daily tasks. The outcomes question whether postoperative instruction can lead to decreasing elbow loads. Future research might focus on reducing elbow loads in the flexion-extension and varus-valgus directions.<br/

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al