The Electric and Magnetic Field Instrument and Integrated Science (EMFISIS) investigation on the NASA Radiation Belt Storm Probes (now named the Van Allen Probes) mission provides key wave and very ...low frequency magnetic field measurements to understand radiation belt acceleration, loss, and transport. The key science objectives and the contribution that EMFISIS makes to providing measurements as well as theory and modeling are described. The key components of the instruments suite, both electronics and sensors, including key functional parameters, calibration, and performance, demonstrate that EMFISIS provides the needed measurements for the science of the RBSP mission. The EMFISIS operational modes and data products, along with online availability and data tools provide the radiation belt science community with one the most complete sets of data ever collected.
The neuromodulator dopamine has a well established role in reporting appetitive prediction errors that are widely considered in terms of learning. However, across a wide variety of contexts, both ...phasic and tonic aspects of dopamine are likely to exert more immediate effects that have been less well characterized. Of particular interest is dopamine's influence on economic risk taking and on subjective well-being, a quantity known to be substantially affected by prediction errors resulting from the outcomes of risky choices. By boosting dopamine levels using levodopa (l-DOPA) as human subjects made economic decisions and repeatedly reported their momentary happiness, we show here an effect on both choices and happiness. Boosting dopamine levels increased the number of risky options chosen in trials involving potential gains but not trials involving potential losses. This effect could be better captured as increased Pavlovian approach in an approach-avoidance decision model than as a change in risk preferences within an established prospect theory model. Boosting dopamine also increased happiness resulting from some rewards. Our findings thus identify specific novel influences of dopamine on decision making and emotion that are distinct from its established role in learning.
In 2017–2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth ...(PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparity's social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a woman's microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB.
Summary
In the face of rapid environmental change, anticipating shifts in microparasite and macroparasite dynamics, including emergence events, is an enormous challenge. We argue that immunological ...studies in natural populations are pivotal to meeting this challenge: many components of environmental change – shifts in biotic assemblages, altered climate patterns and reduced environmental predictability – may affect host immunity. We suggest that wild ungulates can serve as model systems aiding the discovery of immunological mechanisms that link environmental change with parasite transmission dynamics. Our review of eco‐immunological studies in wild ungulates reveals progress in understanding how co‐infections affect immunity and parasite transmission and how environmental and genetic factors interact to shape immunity. Changes in bioavailability of micronutrients have been linked to immunity and health in wild ungulates. Although physiological stress in response to environmental change has been assessed, downstream effects on immunity have not been studied. Moreover, the taxonomic range of ungulates studied is limited to bovids (bighorn sheep, Soay sheep, chamois, musk oxen, bison, African buffalo) and a few cervids (red deer, black‐tailed deer). We discuss areas where future studies in ungulates could lead to significant contributions in understanding the patterns of immunity and infection in natural populations and across species.
To evaluate the protein-binding and signal enhancement characteristics of MS-325, a gadolinium-based magnetic resonance (MR) imaging blood pool agent that binds to albumin, and compare results with ...those obtained with existing gadolinium- and iron oxide-based agents.
Protein binding in human plasma was measured by means of ultrafiltration. T1 relaxation times (20 MHz) were measured in human plasma or ex vivo samples from rabbits and monkeys injected with 0.1 mmol of MS-325 per kilogram of body weight. Imaging (three-dimensional fast imaging with steady-state precession, or FISP) was performed at 1.0 T in phantoms, which contained varying concentrations of different agents, or rabbits after injection of 0.015-0.100 mmol/kg MS-325.
MS-325 is 80%-96% bound in human plasma and exhibits a relaxivity approximately six to 10 times that of gadolinium diethylenetriaminepentaacetic acid (DTPA). Images of phantoms containing MS-325 were significantly brighter than those containing existing gadolinium chelates or iron particles (monocrystalline iron oxide nanoparticle, or MION) at equivalent concentrations. Findings of in vivo studies indicated strong, persistent plasma T1 reduction with MS-325 for 1 hour (T1 of MS-325, 50-100 msec; T1 of Gd-DTPA, 200-400 msec) and strong vascular enhancement on MR images.
MS-325 is highly protein bound after injection and provides vascular signal enhancement superior to that provided with other agents. As the first gadolinium-based blood pool agent in human trials, MS-325 has the potential to enhance both dynamic and steady-state MR angiograms.
Reduced motivation is an important symptom of major depression, thought to impair recovery by reducing opportunities for rewarding experiences. We characterized motivation for monetary outcomes in ...depressed outpatients (N = 39, 22 female) and controls (N = 22, 11 female) in terms of their effectiveness in seeking rewards and avoiding losses. We assessed motivational function during learning of associations between stimuli and actions, as well as when learning was complete. We compared the activity within neural circuits underpinning these behaviors between depressed patients and controls.
We used a Go/No-Go task that assessed subjects' abilities in learning to emit or withhold actions to obtain monetary rewards or avoid losses. We derived motivation-relevant parameters of behavior (learning rate, Pavlovian bias, and motivational influence of gains and losses). After learning, participants performed the task during functional magnetic resonance imaging (fMRI). We compared neural activation during anticipation of action emission vs. action inhibition, and for actions performed to obtain rewards compared to actions that avoid losses.
Depressed patients showed a similar Pavlovian bias to controls and were equivalent in terms of withholding action to gain rewards and emitting action to avoid losses, behaviors that conflict with well-described Pavlovian tendencies to approach rewards and avoid losses. Patients were not impaired in overall performance or learning and showed no abnormal neural responses, for example in bilateral midbrain or striatum. We conclude that basic mechanisms subserving motivated learning are thus intact in moderate depression.
Therapeutically, the intact mechanisms identified here suggest that learning-based interventions may be particularly effective in encouraging recovery. Etiologically, our results suggest that the severe motivational deficits clinically observed in depression are likely to have complex origins, possibly related to an impairment in the representation of future states necessary for long-term planning.
The jewel wasp, Nasonia vitripennis Ashmead (Hymenoptera: Pteromalidae), is an easily reared parasitoid that is providing an ever increasingly malleable model for examining the biology and genetics ...of Hymenoptera. Utilizing genomic and transcriptome resources, 5' upstream transcriptional regulatory sequences (TREs) from three highly expressed genes were identified and cloned. Criteria for TRE selection included the presence of an adjacent gene 5' of the translation initiation site. One gene was methylated whereas the other two were nonmethylated. Each TRE, heat‐shock protein 70 (hsp70), activator of 90 kDa hsp ATPase protein 1 (hsp90A), and lipid storage droplet surface‐binding protein 1 (lsdp) was linked with enhanced green fluorescent protein (EGFP) coding sequence and cloned into both pDP9e somatic and piggyBac germline transformation vectors. EGFP expression patterns under control of each TRE were compared with patterns of DsRed fluorescence produced from the transformation vector cassette. Functional activity of each TRE was observed in cultured Spodoptera frugiperda 9 (Sf9) cells and Drosophila melanogaster as well as in N. vitripennis embryos demonstrating that all three sequences had functional transcriptional regulatory activity in three different insect orders. Identification and functional characterization of these three TREs will provide critical and necessary resources for further genetic analyses of N. vitripennis, Hymenoptera and other insects.
Objective To test the hypothesis that a change in glycated hemoglobin (A1c) over a follow-up interval of approximately 2 years would be associated with concomitant changes in fasting lipids in ...individuals with type 1 diabetes (T1D). Study design All subjects with T1D diagnosed in 2002-2005 in the SEARCH for Diabetes in Youth study with at least 2 study visits ∼12 and ∼24 months after an initial visit were included (age at initial visit, 10.6 ± 4.1 years; 48% female; diabetes duration, 10 ± 7 months; 76% non-Hispanic white; A1c = 7.7% ± 1.4%). Longitudinal mixed models were fit to examine the relationship between change in A1c and change in lipid levels (total cholesterol TC, high-density lipoprotein-cholesterol HDL-c, low-density lipoprotein-cholesterol LDL-c, log triglycerides TG, and non–HDL-c) with adjustment for possible confounders. Results Change in A1c over time was significantly associated with changes in TC, HDL-c, LDL-c, TG, and non–HDL-c over the range of A1c values. For example, for a person with an A1c of 10% and then a 2% decrease in A1c 2 years later (to 8%), the model predicted concomitant changes in TC (−0.29 mmol/L, −11.4 mg/dL), HDL-c (0.03 mmol/L, 1.3 mg/dL), LDL-c (−0.23 mmol/L, −9.0 mg/dL), and non–HDL-c (−0.32 mmol/L, −12.4 mg/dL) and an 8.5% decrease in TG (mmol/L). Conclusions Improved glucose control over a 2-year follow-up was associated with a more favorable lipid profile but may be insufficient to normalize lipids in dyslipidemic T1D youth needing to decrease lipids to goal.
Headline
This is a longitudinal study of a cohort of primigravidae recruited between 1985 and 1987 and followed up 7 and 15 years later. Pelvic floor neurophysiology was performed and questionnaires ...were administered to determine the natural history of stress incontinence and to establish whether pelvic floor denervation after the first delivery is associated with symptoms of stress urinary incontinence in the future.
Objectives
To study the natural history of stress urinary incontinence arising during the first pregnancy, to determine whether postnatal pelvic floor denervation progresses with time and whether it predisposes to stress urinary incontinence in the future.
Design
Prospective longitudinal cohort study.
Setting
Tertiary referral urogynaecology unit.
Sample
Cohort of 96 primigravidae studied prospectively between 1985 and 1987 and followed up 7 years (n= 76) and 15 years (n= 55) later.
Methods
Urinary incontinence symptoms were recorded and pelvic floor neurophysiology was performed antenatally and postnatally between 1985 and 1987. Repeat neurophysiological tests and questionnaires were completed by those relocated 7 and 15 years later.
Main outcome measure
Symptoms of stress urinary incontinence.
Secondary outcomes
Symptoms of urge urinary incontinence and anal incontinence; motor unit potential duration and pudendal nerve terminal latency; vaginal squeeze pressure measured by perineometry.
Results
Prevalence of stress incontinence was highest during pregnancy and had increased seven years after the first postnatal period (P= 0.0129). Two‐thirds of women with antenatal stress incontinence had stress incontinence 15 years later. One‐third of women with stress incontinence at any time appear to undergo resolution of symptoms. Motor unit potential duration increased at seven years (P= 0.036). Vaginal squeeze pressure improved during the same period (P= 0.0007).
Conclusions
When stress urinary incontinence arises during the first pregnancy, the risk of stress incontinence occurring 15 years later is doubled. Although pelvic floor reinnervation progressed after the postnatal period, the absence of an adequate marker for pelvic floor denervation makes it of uncertain clinical significance.
Dissociation, defined as a disruption in usually integrated mental functions, is found not only in DSM-IV dissociative disorders, but also in post-traumatic stress disorder and eating disorders. ...Dissociative phenomena are also common in the general population, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through experiencing adverse life events. In pathological dissociation, evidence has been presented for episodic memory dysfunction. In contrast, in high-dissociative subjects increased performance has been found for episodic memory and dual task performance. These findings have been linked to changes in working memory capacity.
In the present study, the authors sought to extend these findings by using functional magnetic resonance imaging during performance of two parametric working memory tasks. We tested 21 healthy low- and high-dissociative participants.
High-dissociative participants performed slightly better during both tasks. Imaging data showed that both groups activated similar networks for both tasks, i.e. (bilateral) dorsolateral (DL) and ventrolateral prefrontal cortex (PFC), parietal cortex, and supplementary motor area. Group x task interactions were found in the high-dissociative group in L DLPFC and L parietal cortex; in the low-dissociative group in R fusiform gyrus. The differences in the high-dissociative group were independent from performance differences, implying that high-dissociative subjects generally recruit this network to a greater extent.
These results confirm earlier findings using a verbal WM task in high-dissociative participants, and are compatible with the conceptualization of non-pathological dissociation as an information-processing style, characterized by distinct attentional and mnemonic abilities.