Latent heat must be visible in climate communications

C.R.'s portion of the work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). This work used JASMIN, the UK collaborative data analysis facility.Anthropogenic forcing is driving energy accumulation in the Earth system, including increases in the sensible heat content of the atmosphere, as measured by dry-bulb temperature—the metric that is almost universally used for communications about climate change. The atmosphere is also moistening, though, representing an accumulation of latent heat, which is partly concealed by dry-bulb temperature trends. We highlight that, consistent with basic theory, latent heat gains are outpacing sensible heat gains over about half of the Earth's surface. The difference is largest in the tropics, where global “hotspots” of total heat accumulation are located, and where regional disparities in heating rates are very poorly represented by dry-bulb temperatures. Including latent heat in climate-change metrics captures this heat accumulation and therefore improves adaptation-relevant understanding of the extreme humid heat and precipitation hazards that threaten these latitudes so acutely. For example, irrigation can lower peak dry-bulb temperatures, but amplify latent heat content by a larger margin, intensifying dangerous heat stress. Based on a review of the research literature, our Perspective therefore calls for routine use of equivalent temperature, a measure that expresses the combined sensible and latent heat content of the atmosphere in the familiar units of °C or K. We recognize that dry-bulb air temperature must remain a key indicator of the atmospheric state, not least for the many sectors that are sensitive to sensible heat transfer. However, we assert here that more widespread use of equivalent temperature could improve process understanding, public messaging, and adaptation to climate change.Publisher PDFPeer reviewe

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Pharmacotherapy of Schizophrenic Patients: Preponderance of Off-Label Drug Use

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. “Real world” pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs

Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction

Impact of Dendritic Size and Dendritic Topology on Burst Firing in Pyramidal Cells

Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change neuronal burst firing and thus ultimately affect information processing and cognition

Narratives about illness and medication: a neglected theme/new methodology within pharmacy practice research. Part II: Medication narratives in practice

Aim Part 2 of this paper aims to provide a methodological framework for the study of medication narratives, including a semi-structured interview guide and suggested method of analysis, in an attempt to aid the development of narrative scholarship within pharmacy practice research. Examples of medication narratives are provided to illustrate their diversity and usefulness. Methods The framework is derived from the work of other researchers and adapted for our specific purpose. It comes from social psychology, narrative psychology, narrative anthropology, sociology and critical theory and fits within the social constructionist paradigm. The suggested methods of analysis could broadly be described as narrative analysis and discourse analysis. Examples of medication narratives are chosen from a variety of sources and brief interpretations are presented by way of illustration. Conclusion Narrative analysis, a neglected area of research in pharmacy practice, has the potential to provide new understanding about how people relate to their medicines, how pharmacists are engaged in producing narratives and the importance of narrative in the education of students. Impact of the article This article aims to have the following impact on pharmacy practice research: Innovative approach to researching and conceptualising the use of medicines Introduction of a new theoretical perspective and methodology Incorporation of social science research methods into pharmacy practice research Development of narrative scholarship within pharmac

The phenotypic continuum of ATPLA3-related disorders

Background and objectives: ATP1A3 is associated with a broad spectrum of predominantly neurological disorders, that continues to expand beyond the initially defined phenotypes of Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, Sensorineural hearing loss syndrome (CAPOS). This phenotypic variability makes it challenging to assess pathogenicity of an ATP1A3 variant found in an undiagnosed patient. We describe the phenotypic features of individuals carrying a pathogenic/likely pathogenic ATP1A3 variant and perform a literature review of all ATP1A3 variants published thus far in association with human neurological disease. Our aim is to demonstrate the heterogeneous clinical spectrum of the gene and look for phenotypic overlap between patients that will streamline the diagnostic process. Methods: Undiagnosed individuals with ATP1A3 variants were identified within the cohort of the Deciphering Developmental Disorders (DDD) study with additional cases contributed by collaborators internationally. Detailed clinical data was collected with consent through a questionnaire completed by the referring clinicians. PubMed was searched for publications containing the term “ATP1A3” from 2004 to 2021. Results: Twenty-four individuals with a previously undiagnosed neurological phenotype were found to carry 21 ATP1A3 variants. Eight variants have been previously published. Patients experienced on average 2-3 different types of paroxysmal events. Permanent neurological features were common including microcephaly (7;29%), ataxia (13;54%), dystonia (10;42%) and hypotonia (7;29%). All patients had cognitive impairment. Neuropsychiatric diagnoses were reported in 16 (66.6%) individuals. Phenotypes were extremely varied and most individuals did not fit clinical criteria for previously published phenotypes. On review of the literature, 1108 individuals have been reported carrying 168 different ATP1A3 variants. The most common variants are associated with well-defined phenotypes, while more rare variants often result in very rare symptom correlations, such as are seen in our study. CADD scores of pathogenic and likely pathogenic variants were significantly higher and variants clustered within six regions of constraint. Conclusion: Our study shows that looking for a combination of paroxysmal events, hyperkinesia, neuropsychiatric symptoms, and cognitive impairment, as well as evaluating CADD score and variant location can help identify an ATP1A3-related condition, rather than applying diagnostic criteria alone

Intra- and inter-observer reliability in anthropometric measurements in children

Introduction: Studies such as IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) seek to compare data across several different countries. Therefore, it is important to confirm that body composition indices, which are subject to intra- and inter-individual variation, are measured using a standardised protocol that maximises their reliability and reduces error in analyses. Objective: To describe the standardisation and reliability of anthropometric measurements. Both intra- and inter-observer variability of skinfold thickness (triceps, subscapular, biceps, suprailiac) and circumference (neck, arm, waist, hip) measurements were investigated in five different countries. Methods: Central training for fieldwork personnel was carried out, followed by local training in each centre involving the whole survey staff. All technical devices and procedures were standardised. As part of the standardisation process, at least 20 children participated in the intra- and inter-observer reliability test in each centre. A total of 125 children 2-5 years of age and 164 children 6-9 years of age took part in this study, with a mean age of 5.4 (+/- 1.2) years. Results: The intra-observer technical error of measurement (TEM) was between 0.12 and 0.47 mm for skinfold thickness and between 0.09 and 1.24 cm for circumference measurements. Intra-observer reliability was 97.7% for skinfold thickness (triceps, subscapular, biceps, suprailiac) and 94.7% for circumferences (neck, arm, waist, hip). Inter-observer TEMs for skinfold thicknesses were between 0.13 and 0.97 mm and for circumferences between 0.18 and 1.01 cm. Inter-observer agreement as assessed by the coefficient of reliability for repeated measurements of skinfold thickness and circumferences was above 88% in all countries. Conclusion: In epidemiological surveys it is essential to standardise the methodology and train the participating staff in order to decrease measurement error. In the framework of the IDEFICS study, acceptable intra- and inter-observer agreement was achieved for all the measurements. International Journal of Obesity (2011) 35, S45-S51; doi:10.1038/ijo.2011.3