Exploring the Anti-Hypoxaemia Effect of Hydromethylthionine: A Prospective Study of Phase 3 Clinical Trial Participants.

Methylthioninium chloride (MTC) is a standard treatment for methaemoglobinaemia. A preparation of reduced MTC has been reported to increase blood oxygen saturation (SpO2) and lower respiratory rates in patients with severe COVID-19. We have developed a stable form of reduced methylthionine (hydromethylthionine-mesylate, HMTM) having a benign safety profile in two Phase 3 trials in Alzheimer's disease. The aim of this prospective study was to determine the effects of oral HMTM on SpO2 and methaemoglobin (metHb) levels in a cohort of patients with mild hypoxaemia not due to COVID-19. Eighteen participants randomised to a single dose of 4, 75, 100 or 125 mg doses of HMTM had SpO2 levels below 94% at baseline. Patients were routinely monitored by pulse oximetry after 4 h, and after 2 and 6 weeks of twice daily dosing. Significant ~3% increases in SpO2 occurred within 4 h and were sustained over 2 and 6 weeks with no dose differences. There were small dose-dependent increases (0.060-0.162%) in metHb levels over 2 to 6 weeks. Minimum-energy computational chemistry revealed that HMT can bind within 2.10 Å of heme iron by donating a pair of electrons from the central nitrogen of HMT to d orbitals of heme iron, but with lower affinity than oxygen. In conclusion, HMTM can increase SpO2 without reducing metHb by acting as a strong displaceable field ligand for heme iron. We hypothesise that this facilitates a transition from the low oxygen affinity T-state of heme to the higher affinity R-state. HMTM has potential as an adjunctive treatment for hypoxaemia.

Multidecadal climate oscillations during the past millennium driven by volcanic forcing.

Past research argues for an internal multidecadal (40- to 60-year) oscillation distinct from climate noise. Recent studies have claimed that this so-termed Atlantic Multidecadal Oscillation is instead a manifestation of competing time-varying effects of anthropogenic greenhouse gases and sulfate aerosols. That conclusion is bolstered by the absence of robust multidecadal climate oscillations in control simulations of current-generation models. Paleoclimate data, however, do demonstrate multidecadal oscillatory behavior during the preindustrial era. By comparing control and forced "Last Millennium" simulations, we show that these apparent multidecadal oscillations are an artifact of pulses of volcanic activity during the preindustrial era that project markedly onto the multidecadal (50- to 70-year) frequency band. We conclude that there is no compelling evidence for internal multidecadal oscillations in the climate system.

Absence of internal multidecadal and interdecadal oscillations in climate model simulations.

For several decades the existence of interdecadal and multidecadal internal climate oscillations has been asserted by numerous studies based on analyses of historical observations, paleoclimatic data and climate model simulations. Here we use a combination of observational data and state-of-the-art forced and control climate model simulations to demonstrate the absence of consistent evidence for decadal or longer-term internal oscillatory signals that are distinguishable from climatic noise. Only variability in the interannual range associated with the El Niño/Southern Oscillation is found to be distinguishable from the noise background. A distinct (40-50 year timescale) spectral peak that appears in global surface temperature observations appears to reflect the response of the climate system to both anthropogenic and natural forcing rather than any intrinsic internal oscillation. These findings have implications both for the validity of previous studies attributing certain long-term climate trends to internal low-frequency climate cycles and for the prospect of decadal climate predictability.

Projected changes in persistent extreme summer weather events: The role of quasi-resonant amplification.

Persistent episodes of extreme weather in the Northern Hemisphere summer have been associated with high-amplitude quasi-stationary atmospheric Rossby waves, with zonal wave numbers 6 to 8 resulting from the phenomenon of quasi-resonant amplification (QRA). A fingerprint for the occurrence of QRA can be defined in terms of the zonally averaged surface temperature field. Examining state-of-the-art [Coupled Model Intercomparison Project Phase 5 (CMIP5)] climate model projections, we find that QRA events are likely to increase by ~50% this century under business-as-usual carbon emissions, but there is considerable variation among climate models. Some predict a near tripling of QRA events by the end of the century, while others predict a potential decrease. Models with amplified Arctic warming yield the most pronounced increase in QRA events. The projections are strongly dependent on assumptions regarding the nature of changes in radiative forcing associated with anthropogenic aerosols over the next century. One implication of our findings is that a reduction in midlatitude aerosol loading could actually lead to Arctic de-amplification this century, ameliorating potential increases in persistent extreme weather events.

Effectiveness of an Educational Module on Dental Hygiene Students' Attitudes Towards Persons with Disabilities.

Purpose: Persons with disabilities (PWDs) perceive gaps in health care providers' understanding of their health care needs are more likely to delay or not seek health care as compared to persons without disabilities. Oral health is considered an essential component of overall health, however, disparities exist in the United States, especially for persons with disabilities. Improving the education and training of dentists and dental hygienists may contribute to reducing oral health care barriers for PWDs. The purpose of this study was to investigate whether offering an education module about individuals with disabilities would change dental hygiene students' attitudes and capacity for informed empathy for PWDs.Methods: An educational module utilizing a DVD featuring authentic representation of PWDs, along with student discussions and self-reflection was developed and delivered to 165 (n=165) dental hygiene students attending a 2-year community college and a 4-year university. Students consenting to participate in the study were assessed regarding their attitudes and comfort towards caring for PWDs prior to, and following the educational module. Pre- and post-assessment measures included the validated Attitude Toward Disabled Persons, and Attitudes toward Patient Advocacy Microsocial (AMIA) scale. The Interpersonal Reactivity Index (IRI) was used as a pre-assessment measure.Results: A total of 58 (n=58) dental hygiene students, 35 (n=35) from a 4-year university and 23 (n=23) from a 2-year community college, consented for this study, for an overall participation rate of 35%. Scores increased significantly for both student groups after delivering the education module on the AMIA patient advocacy scale. Differences in IRI scores between the 2-year and 4-year dental hygiene programs approached statistical significance.Conclusion: An education module based on informed empathy with a focus on the experiences of PWDs can result in improved attitudes toward advocacy for this population.

Corrigendum: Influence of Anthropogenic Climate Change on Planetary Wave Resonance and Extreme Weather Events.

This corrects the article DOI: 10.1038/srep45242.

Influence of Anthropogenic Climate Change on Planetary Wave Resonance and Extreme Weather Events.

Persistent episodes of extreme weather in the Northern Hemisphere summer have been shown to be associated with the presence of high-amplitude quasi-stationary atmospheric Rossby waves within a particular wavelength range (zonal wavenumber 6-8). The underlying mechanistic relationship involves the phenomenon of quasi-resonant amplification (QRA) of synoptic-scale waves with that wavenumber range becoming trapped within an effective mid-latitude atmospheric waveguide. Recent work suggests an increase in recent decades in the occurrence of QRA-favorable conditions and associated extreme weather, possibly linked to amplified Arctic warming and thus a climate change influence. Here, we isolate a specific fingerprint in the zonal mean surface temperature profile that is associated with QRA-favorable conditions. State-of-the-art ("CMIP5") historical climate model simulations subject to anthropogenic forcing display an increase in the projection of this fingerprint that is mirrored in multiple observational surface temperature datasets. Both the models and observations suggest this signal has only recently emerged from the background noise of natural variability.

The Likelihood of Recent Record Warmth.

2014 was nominally the warmest year on record for both the globe and northern hemisphere based on historical records spanning the past one and a half centuries. It was the latest in a recent run of record temperatures spanning the past decade and a half. Press accounts reported odds as low as one-in-650 million that the observed run of global temperature records would be expected to occur in the absence of human-caused global warming. Press reports notwithstanding, the question of how likely observed temperature records may have have been both with and without human influence is interesting in its own right. Here we attempt to address that question using a semi-empirical approach that combines the latest (CMIP5) climate model simulations with observations of global and hemispheric mean temperature. We find that individual record years and the observed runs of record-setting temperatures were extremely unlikely to have occurred in the absence of human-caused climate change, though not nearly as unlikely as press reports have suggested. These same record temperatures were, by contrast, quite likely to have occurred in the presence of anthropogenic climate forcing.

From Impairment to Empowerment: A Longitudinal Medical School Curriculum on Disabilities.

PROBLEM: All physicians will care for individuals with disabilities; however, education about disabilities is lacking at most medical schools. Most of the schools that do include such education exclusively teach the medical model, in which disability is viewed as an impairment to be overcome. Disability advocates contest this approach because it overlooks the social and societal contexts of disability. A collaboration between individuals with disabilities, educators, and physicians to design a medical school curriculum on disabilities could overcome these differences. APPROACH: A curriculum on disabilities for first- and second-year medical students was developed during the 2013-2014 academic year and involved a major collaboration between a medical student, medical educators, disability advocates, and academic disability specialists. The guiding principle of the project was the Disability Rights Movement motto, "Nothing about us without us." Two small-group sessions were created, one for each medical school class. They included discussions about different models of disability, video and in-person narratives of individuals with disabilities, and explorations of concepts central to social perceptions of disability, such as power relationships, naming and stigmatization, and disability as identity. OUTCOMES: According to evaluations conducted after each session, students reported positive feedback about both sessions. NEXT STEPS: Through this curriculum, first- and second-year medical students learned about the obstacles faced by individuals with disabilities and became better equipped to understand and address the concerns, hopes, and societal challenges of their future patients. This inclusive approach may be used to design additional curricula about disabilities for the clinical and postgraduate years.

Ozone profiles in the Baltimore-Washington region (2006-2011): satellite comparisons and DISCOVER-AQ observations.

Much progress has been made in creating satellite products for tracking the pollutants ozone and NO2 in the troposphere. Yet, in mid-latitude regions where meteorological interactions with pollutants are complex, accuracy can be difficult to achieve, largely due to persistent layering of some constituents. We characterize the layering of ozone soundings and related species measured from aircraft over two ground sites in suburban Washington, DC (Beltsville, MD, 39.05 N; 76.9 W) and Baltimore (Edgewood, MD, 39.4 N; 76.3 W) during the July 2011 DISCOVER-AQ (Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality) experiment. First, we compare column-ozone amounts from the Beltsville and Edgewood sondes with data from overpassing satellites. Second, processes influencing ozone profile structure are analyzed using Laminar Identification and tracers: sonde water vapor, aircraft CO and NOy. Third, Beltsville ozone profiles and meteorological influences in July 2011 are compared to those from the summers of 2006-2010. Sonde-satellite offsets in total ozone during July 2011 at Edgewood and Beltsville, compared to the Ozone Monitoring Instrument (OMI), were 3 % mean absolute error, not statistically significant. The disagreement between an OMI/Microwave Limb Sounder-based tropospheric ozone column and the sonde averaged 10 % at both sites, with the sonde usually greater than the satellite. Laminar Identification (LID), that distinguishes ozone segments influenced by convective and advective transport, reveals that on days when both stations launched ozonesondes, vertical mixing was stronger at Edgewood. Approximately half the lower free troposphere sonde profiles have very dry laminae, with coincident aircraft spirals displaying low CO (80-110 ppbv), suggesting stratospheric influence. Ozone budgets at Beltsville in July 2011, determined with LID, as well as standard meteorological indicators, resemble those of 4 of the previous 5 summers. The penetration of stratospheric air throughout the troposphere appears to be typical for summer conditions in the Baltimore-Washington region.

Fostering informed empathy through patient-centred education about persons with disabilities.

INTRODUCTION: Having a disability can negatively affect provider-patient communication. Persons with disabilities report the need for better communication with their health care providers and argue that education regarding disabilities is lacking for health care professionals. We sought to determine if a patient-centred curriculum focused on individuals with disabilities could foster the development of informed empathy. METHODS: An educational module to enhance health care students' capacity for informed empathy was developed. To assess the development of informed empathy, a qualitative analysis of the post-module question, 'How has your understanding, awareness or perception of individuals with disabilities changed?' was performed. RESULTS: Themes of the qualitative analysis were (a) becoming familiar with the daily life of individuals with disabilities, (b) changing notions of normalcy, (c) seeing discrimination against individuals with disabilities as an issue that impacted them, (d) recognition that disability is not only an issue of the physical body. CONCLUSIONS: Informed empathy can be effectively taught through a patient-centred curriculum focused on persons with disabilities. Health care providers are effective advocates when they understand the physical, emotional, social, and communication issues of persons with disabilities.

Climate change. Atlantic and Pacific multidecadal oscillations and Northern Hemisphere temperatures.

The recent slowdown in global warming has brought into question the reliability of climate model projections of future temperature change and has led to a vigorous debate over whether this slowdown is the result of naturally occurring, internal variability or forcing external to Earth's climate system. To address these issues, we applied a semi-empirical approach that combines climate observations and model simulations to estimate Atlantic- and Pacific-based internal multidecadal variability (termed "AMO" and "PMO," respectively). Using this method, the AMO and PMO are found to explain a large proportion of internal variability in Northern Hemisphere mean temperatures. Competition between a modest positive peak in the AMO and a substantially negative-trending PMO are seen to produce a slowdown or "false pause" in warming of the past decade.

A curriculum focused on informed empathy improves attitudes toward persons with disabilities.

Empathy is an important component of the provider-patient relationship. In the United States one in five persons has a disability. Persons with disabilities perceive gaps in health care providers' understanding of their health care preferences and needs. The purpose of this study was to use valid and reliable assessment methods to investigate the association between empathy and attitudes toward persons with disabilities and advocacy. An educational module was developed to enhance health care students' capacity for informed empathy. Pre- and post-assessment measures included the Attitude toward Disabled Persons scale (ATDP), the Attitudes toward Patient Advocacy Microsocial scale (AMIA) and the Interpersonal Reactivity Index (IRI). ATDP (t(94) = -5.95, p = .000) and AMIA (t(92) = -5.99, p = .000) scores increased significantly after the education module. Correlations between the pre- or post-module ATDP or AMIA scores and the IRI scores were not significant. Empathy in general may not be sufficient to ensure optimal attitudes toward persons with disabilities or advocacy in pre-health care professionals. However, a curriculum based on informed empathy and focused on the experiences of persons with disabilities can result in more positive attitudes toward and advocacy for people with disabilities.

A qualitative study of the perspectives of individuals with disabilities about their health care experiences: implications for culturally appropriate health care.

PURPOSE: This study explores the health care experience of individuals with disabilities and how this knowledge can guide health care professionals in providing effective and compassionate care for persons with disabilities. METHODS: Participants' experiences about the health care they received were quantitatively analyzed for common themes. RESULTS: Participants most often discussed the process of how they came to receive their official disability diagnosis. Another recurrent theme was disability etiology, in which participants described the events or process that resulted in a disability. Two other frequent themes, normality and others' perceptions of disability, centered upon what it means to be "normal" or others' assumptions about what it means to be "nor mal" (as opposed to having a disability). Family support and struggles, experiences with medical professionals and hospitals, and barriers to inclusion and accommodations were the other key themes. CONCLUSION: This study provides insights to aspects of living with a disability that individuals with disabilities felt were important for health care professionals to know. Being aware of these topics may help health care providers in establishing good communication with their patients who have a disability.

Proxy-based reconstructions of hemispheric and global surface temperature variations over the past two millennia.

Following the suggestions of a recent National Research Council report [NRC (National Research Council) (2006) Surface Temperature Reconstructions for the Last 2,000 Years (Natl Acad Press, Washington, DC).], we reconstruct surface temperature at hemispheric and global scale for much of the last 2,000 years using a greatly expanded set of proxy data for decadal-to-centennial climate changes, recently updated instrumental data, and complementary methods that have been thoroughly tested and validated with model simulation experiments. Our results extend previous conclusions that recent Northern Hemisphere surface temperature increases are likely anomalous in a long-term context. Recent warmth appears anomalous for at least the past 1,300 years whether or not tree-ring data are used. If tree-ring data are used, the conclusion can be extended to at least the past 1,700 years, but with additional strong caveats. The reconstructed amplitude of change over past centuries is greater than hitherto reported, with somewhat greater Medieval warmth in the Northern Hemisphere, albeit still not reaching recent levels.

Popliteal aneurysm as a source of phantom pain: a case report.

A 42-year-old man with a remote history of right transtibial amputation but no history of phantom pain developed severe phantom pain 10 years after amputation. A literature review suggested that his presentation was contrary to the natural history of phantom pain, which is usually most prominent in the early stages after amputation. Diagnostic workup revealed a popliteal artery aneurysm, which was successfully treated with coil embolization. The patient had complete resolution of his phantom pain after treatment of the aneurysm, suggesting it was the source of the pain. As a result of successful diagnosis and treatment, the amputation level did not need to be revised and the patient was able to continue his previously high level of function.