Hyper-Palatable Foods: Development of a Quantitative Definition and Application to the US Food System Database

Objective: Extensive research has focused on hyper-palatable foods (HPF); however, HPF are defined using descriptive terms (e.g., fast foods, sweets), which are not standardized and lack specificity. The study purpose was to develop a quantitative definition of HPF and apply the definition to the Food and Nutrient Database for Dietary Studies (FNDDS) to determine HPF prevalence in the US food system. Methods: A numeric definition of HPF was developed by extracting common HPF descriptive definitions from the literature and using nutrition software to quantify ingredients of fat, simple sugars, carbohydrates, and sodium. The definition was applied to the FNDDS. Results: HPF from the literature aligned with three clusters: (1) fat and sodium (> 25% kcal from fat, ≥ 0.30% sodium by weight), (2) fat and simple sugars (> 20% kcal from fat, > 20% kcal from sugar), and (3) carbohydrates and sodium (> 40% kcal from carbohydrates, ≥ 0.20% sodium by weight). In the FNDDS, 62% (4,795/7,757) of foods met HPF criteria. The HPF criteria identified a variety of foods, including some labeled reduced or low fat and vegetables cooked in creams, sauces, or fats. Conclusions: A data-derived HPF definition revealed that a substantial percentage of foods in the US food system may be hyper-palatable, including foods not previously conceptualized as hyper-palatable

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17β-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17β-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17β-estradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia 1 (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17β-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17β-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17β-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon. Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number

Ectoplasm with an Edge

The construction of supersymmetric invariant actions on a spacetime manifold with a boundary is carried out using the "ectoplasm" formalism for the construction of closed forms in superspace. Non-trivial actions are obtained from the pull-backs to the bosonic bodies of closed but non-exact forms in superspace; finding supersymmetric invariants thus becomes a cohomology problem. For a spacetime with a boundary, the appropriate mathematical language changes to relative cohomology, which we use to give a general formulation of off-shell supersymmetric invariants in the presence of boundaries. We also relate this construction to the superembedding formalism for the construction of brane actions, and we give examples with bulk spacetimes of dimension 3, 4 and 5. The closed superform in the 5D example needs to be constructed as a Chern-Simons type of invariant, obtained from a closed 6-form displaying Weil triviality.Comment: 25 page

Improvements in 25 Years of Implantable Cardioverter Defibrillator Therapy

In 1980, Dr. Michel Mirowski and his team inserted the first implantable cardioverter defibrillator (ICD) in a patient. Initially, ICD therapy was not widely accepted, and many physicians actually considered this therapy unethical. Large secondary and primary prevention trials, demonstrating a beneficial effect of ICD therapy in selected patients not only on arrhythmic death but also on all-cause mortality, stimulated a rapid growth in the number of implants and increased patient’s and physician’s acceptance. Improvements in size and weight, arrhythmia discrimination capabilities, battery technology, shock waveform and output, monitoring capabilities and defibrillator electrode technology eventually resulted in the current large number of yearly implants. Today, almost 40 years after the conception of the ICD and 25 years after the first human implant, ICD therapy is the treatment of choice for patients at risk for life-threatening arrhythmias either as secondary or primary prevention. Furthermore, with the more recent addition of resynchronisation therapy to standard ICD therapy, it became possible to treat selected patients with advanced symptoms of heart failure and to lower the risk of sudden death

The global-scale impacts of climate change on water resources and flooding under new climate and socio-economic scenarios

This paper presents a preliminary assessment of the relative effects of rate of climate change (four Representative Concentration Pathways - RCPs), assumed future population (five Shared Socio-economic Pathways - SSPs), and pattern of climate change (19 CMIP5 climate models) on regional and global exposure to water resources stress and river flooding. Uncertainty in projected future impacts of climate change on exposure to water stress and river flooding is dominated by uncertainty in the projected spatial and seasonal pattern of change in climate. There is little clear difference in impact between RCP2.6, RCP4.5 and RCP6.0 in 2050, and between RCP4.5 and RCP6.0 in 2080. Impacts under RCP8.5 are greater than under the other RCPs in 2050 and 2080. For a given RCP, there is a difference in the absolute numbers of people exposed to increased water resources stress or increased river flood frequency between the five SSPs. With the ‘middle-of-the-road’ SSP2, climate change by 2050 would increase exposure to water resources stress for between approximately 920 and 3400 million people under the highest RCP, and increase exposure to river flood risk for between 100 and 580 million people. Under RCP2.6, exposure to increased water scarcity would be reduced in 2050 by 22-24%, compared to impacts under the RCP8.5, and exposure to increased flood frequency would be reduced by around 16%. The implications of climate change for actual future losses and adaptation depend not only on the numbers of people exposed to changes in risk, but also on the qualitative characteristics of future worlds as described in the different SSPs. The difference in ‘actual’ impact between SSPs will therefore be greater than the differences in numbers of people exposed to impact

First experience with the wearable cardioverter defibrillator in the Netherlands

The implantable cardioverter defibrillator (ICD) has significantly improved survival in patients with an increased risk of sudden cardiac death (SCD). The wearable cardioverter defibrillator (WCD) is an alternative to the ICD in patients with a transient ICD indication or those in whom an ICD temporarily cannot be implanted. We describe here the technical details of the WCD and report three patients who were treated with a WCD in an outpatient setting. The WCD allowed the cardiac condition of two patients to improve to such an extent that permanent ICD implantation was deemed unnecessary. This new form of therapy may result in significant cost reduction, avoidance of unnecessary ICD implantation, and increased patient satisfaction

Factor VIII cross-matches to the human proteome reduce the predicted inhibitor risk in missense mutation hemophilia A.

Single missense mutations in the F8 gene encoding the coagulation protein factor VIII (FVIII) give rise predominantly to non-severe hemophilia A. Despite only a single amino acid sequence difference between the replacement, therapeutic FVIII (tFVIII) and the patient's endogenous FVIII, tFVIII may still be perceived as foreign by the recipient's immune system and trigger an immune response (inhibitor). Inhibitor formation is a life-long risk for non-severe hemophilia A patients treated with tFVIII, but remains difficult to predict. The aim of this study was to understand whether fortuitous, primary sequence cross-matches between tFVIII and proteins in the human proteome are the reason why certain F8 mutations are not associated with inhibitor formation. We predicted which tFVIII differences are potentially perceived as foreign by helper T cells a necessary precursor to inhibitor development and then scanned potentially immunogenic peptides against more than 100,000 proteins in the proteome. As there are hundreds of disease-causing F8 missense mutations and the Human Leucocyte Antigen gene complex governing peptide presentation to helper T cells is highly polymorphic, these calculations pose a huge combinatorial challenge that we addressed computationally. We identify that cross-matches between tFVIII and the human proteome are commonplace and have a profound impact on the predicted risk of inhibitor development. Our results emphasize the importance of knowing both the F8 missense mutation and the Human Leucocyte Antigen alleles of a patient with missense mutation hemophilia A if his underlying risk of inhibitor development is to be estimated

Improved methods using the reverse transcriptase polymerase chain reaction to detect tumour cells

Reverse transcriptase polymerase chain reaction (RT-PCR) is increasingly used to detect small numbers of circulating tumour cells, though the clinical benefit remains controversial. The largest single contributing factor to the controversy of its value is the different approaches to sample processing. The aim of this study was to compare the sensitivity and reproducibility of RT-PCR for the detection of tumour cells after four commonly used different methods of sample processing. Using RT-PCR, one tumour cell spiked in 2 ml of whole blood was detected after analysis of separated mononuclear cell RNA, whole blood total or poly-A+RNA. No false positives were identified with any method. However, the reproducibility of tumour cell detection was reduced after isolation of the mononuclear cell fraction. Only analysis of poly-A+RNA had a sensitivity of 100% in all the cell spiking experiments. In patient blood samples, analysis of poly-A+RNA increased the number of blood samples positive for tyrosine hydroxylase (TH) mRNA compared with those positive after analysis of total RNA. This may reflect high levels of cDNA reducing the efficiency of the PCR. Isolation of poly-A+RNA increases the sensitivity and reproducibility of tumour cell detection in peripheral blood. © 1999 Cancer Research Campaig

A novel in-ear sensor to determine sleep latency during the Multiple Sleep Latency Test in healthy adults with and without sleep restriction

Objectives: Detecting sleep latency during the Multiple Sleep Latency Test (MSLT) using electroencephalogram (scalp-EEG) is time-consuming. The aim of this study was to evaluate the efficacy of a novel in-ear sensor (in-ear EEG) to detect the sleep latency, compared to scalp-EEG, during MSLT in healthy adults, with and without sleep restriction. Methods: We recruited 25 healthy adults (28.5±5.3 years) who participated in two MSLTs with simultaneous recording of scalp and in-ear EEG. Each test followed a randomly assigned sleep restriction (≤5 hours sleep) or usual night sleep (≥7 hours sleep). Reaction time and Stroop test were used to assess the functional impact of the sleep restriction. The EEGs were scored blind to the mode of measurement and study conditions, using American Academy of Sleep Medicine 2012 criteria. The Agreement between the scalp and in-ear EEG was assessed using Bland-Altman analysis. Results: Technically acceptable data were obtained from 23 adults during 69 out of 92 naps in the sleep restriction condition and 25 adults during 85 out of 100 naps in the usual night sleep. Meaningful sleep restrictions were confirmed by an increase in the reaction time (mean ± SD: 238±30 ms vs 228±27 ms; P=0.045). In the sleep restriction condition, the in-ear EEG exhibited a sensitivity of 0.93 and specificity of 0.80 for detecting sleep latency, with a substantial agreement (κ=0.71), whereas after the usual night’s sleep, the in-ear EEG exhibited a sensitivity of 0.91 and specificity of 0.89, again with a substantial agreement (κ=0.79). Conclusion: The in-ear sensor was able to detect reduced sleep latency following sleep restriction, which was sufficient to impair both the reaction time and cognitive function. Substantial agreement was observed between the scalp and in-ear EEG when measuring sleep latency. This new in-ear EEG technology is shown to have a significant value as a convenient measure for sleep latency

The Scenario Model Intercomparison Project (ScenarioMIP) for CMIP6

Model experiment description paperProjections of future climate change play a fundamental role in improving understanding of the climate system as well as characterizing societal risks and response options. The Scenario Model Intercomparison Project (ScenarioMIP) is the primary activity within Phase 6 of the Coupled Model Intercomparison Project (CMIP6) that will provide multi-model climate projections based on alternative scenarios of future emissions and land use changes produced with integrated assessment models. In this paper, we describe ScenarioMIP's objectives, experimental design, and its relation to other activities within CMIP6. The ScenarioMIP design is one component of a larger scenario process that aims to facilitate a wide range of integrated studies across the climate science, integrated assessment modeling, and impacts, adaptation, and vulnerability communities, and will form an important part of the evidence base in the forthcoming Intergovernmental Panel on Climate Change (IPCC) assessments. At the same time, it will provide the basis for investigating a number of targeted science and policy questions that are especially relevant to scenario-based analysis, including the role of specific forcings such as land use and aerosols, the effect of a peak and decline in forcing, the consequences of scenarios that limit warming to below 2 °C, the relative contributions to uncertainty from scenarios, climate models, and internal variability, and long-term climate system outcomes beyond the 21st century. To serve this wide range of scientific communities and address these questions, a design has been identified consisting of eight alternative 21st century scenarios plus one large initial condition ensemble and a set of long-term extensions, divided into two tiers defined by relative priority. Some of these scenarios will also provide a basis for variants planned to be run in other CMIP6-Endorsed MIPs to investigate questions related to specific forcings. Harmonized, spatially explicit emissions and land use scenarios generated with integrated assessment models will be provided to participating climate modeling groups by late 2016, with the climate model simulations run within the 2017-2018 time frame, and output from the climate model projections made available and analyses performed over the 2018-2020 period.CRESCENDO project members (V. Eyring, P. Friedlingstein, E. Kriegler, R. Knutti, J. Lowe, K. Riahi, D. van Vuuren) acknowledge funding received from the Horizon 2020 European Union’s Framework Programme for Research and Innovation under grant agreement no. 641816. C. Tebaldi, G. A. Meehl and B. M. Sanderson acknowledge the support of the Regional and Global Climate Modeling Program (RGCM) of the U.S. Department of Energy’s, Office of Science (BER), Cooperative Agreement DE-FC02-97ER6240