Evaluating Strategies For Reducing Health Disparities By Addressing The Social Determinants Of Health

Research reveals that the opportunities for healthy choices in homes, neighborhoods, schools, and workplaces can have decisive impacts on health. This article reviews scientific evidence from promising interventions focused on the social determinants of health, and describes ways in which they can improve population health and reduce health disparities. We show that there is sufficient evidence to support policy interventions targeted at education and early childhood; urban planning and community development; housing; income enhancements and supplements; and employment. When available, cost-effectiveness evaluations show that these interventions lead to long-term societal savings; however, more routine attention to cost considerations is needed for these interventions. We also discuss challenges to implementation, including the need for long-term financing in order to scale-up effective interventions for implementation at the local, state, or national level. Although we know enough to act, questions remain about how to optimally scale-up these interventions and maximize their benefits for the most vulnerable populations

The effect of stress on the expression of the amyloid precursor protein in rat brain

AbstractThe abnormal processing of the amyloid precursor protein (APP) is a pivotal event in the development of the unique pathology that defines Alzheimer's disease (AD). Stress, and the associated increase in corticosteroids, appear to accelerate brain ageing and may increase vulnerability to Alzheimer's disease via altered APP processing. In this study, rats were repeatedly exposed to an unavoidable stressor, an open elevated platform. Previous studies in this laboratory have shown that a single exposure produces a marked increase in plasma corticosterone levels but animals develop tolerance to this effect between 10 and 20 daily sessions. Twenty-four hours after stress, there was an increase in the ratio of the deglycosylated form of APP in the particulate fraction of the brain, which subsequently habituated after 20 days. The levels of soluble APP (APPs) tended to be lower in the stress groups compared to controls except for a significant increase in the hippocampus after 20 days of platform exposure. Since APPs is reported to have neurotrophic properties, this increased release may represent a neuroprotective response to repeated stress. It is possible that the ability to mount this response decreases with age thus increasing the vulnerability to stress-induced AD-related pathology

Can vitamin D status influence the effect of stress on planning and problem-solving? A randomized control trial

Background: Nutritional interventions may serve as a stress resilience strategy with important implications for human health.Objective: The aim of this study was to investigate the effect of vitamin D supplementation throughout wintertime on problem-solving and planning abilities during stressful circumstances.Design: A total of 77 male inpatients with a mean age of 48 years (range 31–81) and stress-related mental health disorders were randomly assigned into a Vitamin D supplement group (daily intake of 40 μg) or a pla-cebo supplement group (Control) (daily intake of 120 mg olive oil). The intervention period was from January 2018 to May 2018. The means and standard deviations for vitamin D status (25-hydroxyvitamin D3, nmol/L), pre- and post-test, respectively, were 58(21) and 46(15) for the Control group, and 63(18) and 76(21) for the Vitamin D group. Problem-solving and planning abilities were measured by the Tower of London (ToL) task pre- (midwinter) and post- (spring) supplement intervention. The ToL task was performed during exposure to distracting noise.Results: The results revealed that vitamin D supplementation throughout the winter had a significant effect on number of correct responses on easier (1 and 2 move) ToL problems during stress; the Vitamin D group improved significantly from pre- to post-test, whereas the Control group did not. In addition, the Vitamin D group had significantly more correct responses than the Control group on post-test. The improved perfor-mance was not related to a speed-accuracy trade off effect; both groups showed significantly decreased plan-ning times from pre- to post-test. The intervention did not differentially affect task performance on the more difficult (3 to 5 move) ToL problems. For the more demanding problems, IQ seemed to explain most of the variance regarding accuracy. Age explained most of the variance associated with task planning time.Conclusion: Vitamin D supplementation seemed to improve resilience to stress, but it was limited to performance of easier tasks.publishedVersio

Mapping preictal and ictal haemodynamic networks using video-electroencephalography and functional imaging

Ictal patterns on scalp-electroencephalography are often visible only after propagation, therefore rendering localization of the seizure onset zone challenging. We hypothesized that mapping haemodynamic changes before and during seizures using simultaneous video-electroencephalography and functional imaging will improve the localization of the seizure onset zone. Fifty-five patients with ≥2 refractory focal seizures/day, and who had undergone long-term video-electroencephalography monitoring were included in the study. ‘Preictal' (30 s immediately preceding the electrographic seizure onset) and ictal phases, ‘ictal-onset'; ‘ictalestablished' and ‘late ictal', were defined based on the evolution of the electrographic pattern and clinical semiology. The functional imaging data were analysed using statistical parametric mapping to map ictal phase-related haemodynamic changes consistent across seizures. The resulting haemodynamic maps were overlaid on co-registered anatomical scans, and the spatial concordance with the presumed and invasively defined seizure onset zone was determined. Twenty patients had typical seizures during functional imaging. Seizures were identified on video-electroencephalography in 15 of 20, on electroencephalography alone in two and on video alone in three patients. All patients showed significant ictal-related haemodynamic changes. In the six cases that underwent invasive evaluation, the ictal-onset phase-related maps had a degree of concordance with the presumed seizure onset zone for all patients. The most statistically significant haemodynamic cluster within the presumed seizure onset zone was between 1.1 and 3.5 cm from the invasively defined seizure onset zone, which was resected in two of three patients undergoing surgery (Class I post-surgical outcome) and was not resected in one patient (Class III post-surgical outcome). In the remaining 14 cases, the ictal-onset phase-related maps had a degree of concordance with the presumed seizure onset zone in six of eight patients with structural-lesions and five of six non-lesional patients. The most statistically significant haemodynamic cluster was localizable at sub-lobar level within the presumed seizure onset zone in six patients. The degree of concordance of haemodynamic maps was significantly better (P < 0.05) for the ictal-onset phase [entirely concordant/concordant plus (13/20; 65%) + some concordance (4/20; 20%) = 17/20; 85%] than ictal-established [entirely concordant/concordant plus (5/13; 38%) + some concordance (4/13; 31%) = 9/13; 69%] and late ictal [concordant plus (1/9; 11%) + some concordance (4/9; 44%) = 5/9; 55%] phases. Ictal propagation-related haemodynamic changes were also seen in symptomatogenic areas (9/20; 45%) and the default mode network (13/20; 65%). A common pattern of preictal changes was seen in 15 patients, starting between 98 and 14 s before electrographic seizure onset, and the maps had a degree of concordance with the presumed seizure onset zone in 10 patients. In conclusion, preictal and ictal haemodynamic changes in refractory focal seizures can non-invasively localize seizure onset at sub-lobar/gyral level when ictal scalp-electroencephalography is not helpfu

With or without spikes: localization of focal epileptic activity by simultaneous electroencephalography and functional magnetic resonance imaging

In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40-70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode array

Vitamin D supplementation during winter: Effects on stress resilience in a randomized control trial

Vitamin D status may be important for stress resilience. This study investigated the effects of vitamin D supplements during winter on biological markers of stress resilience such as psychophysiological activity, serotonin, and cortisol in a placebo-controlled, randomized clinical trial. Eighty-six participants were randomly assigned to the Intervention (vitamin D) or Control (placebo) groups. Before and after the intervention participants were exposed to an experimental stress procedure. Psychophysiological activity was measured during three main conditions: baseline, stress, and recovery. Fasting blood samples were taken in the morning and saliva samples were collected at seven different time points across 24 h. Prior to intervention both groups had normal/sufficient vitamin D levels. Both groups showed a normal pattern of psychophysiological responses to the experimental stress procedure (i.e., increased psychophysiological responses from resting baseline to stress-condition, and decreased psychophysiological responses from stress-condition to recovery; all p < 0.009). Post-intervention, the Intervention group showed increased vitamin D levels (p < 0.001) and normal psychophysiological responses to the experimental stress procedure (p < 0.001). Importantly, the Control group demonstrated a classic nadir in vitamin D status post-intervention (spring) (p < 0.001) and did not show normal psychophysiological responses. Thus, physiologically the Control group showed a sustained stress response. No significant effects of vitamin D were found on serotonin and cortisol.publishedVersio

The Lick AGN Monitoring Project: Reverberation Mapping of Optical Hydrogen and Helium Recombination Lines

We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7M_sun and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad Hbeta emission, which we have previously reported. We present here the light curves for the Halpha, Hgamma, HeII 4686, and HeI 5876 emission lines and the time lags for the emission-line responses relative to changes in the continuum flux. Combining each emission-line time lag with the measured width of the line in the variable part of the spectrum, we determine a virial mass of the central supermassive black hole from several independent emission lines. We find that the masses are generally consistent within the uncertainties. The time-lag response as a function of velocity across the Balmer line profiles is examined for six of the AGNs. Finally we compare several trends seen in the dataset against the predictions from photoionization calculations as presented by Korista & Goad. We confirm several of their predictions, including an increase in responsivity and a decrease in the mean time lag as the excitation and ionization level for the species increases. Further confirmation of photoionization predictions for broad-line gas behavior will require additional monitoring programs for these AGNs while they are in different luminosity states. [abridged]Comment: 37 pages, 18 figures and 15 tables, accepted for publication in the Astrophysical Journa

The Lick AGN Monitoring Project: Broad-Line Region Radii and Black Hole Masses from Reverberation Mapping of Hbeta

We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7 M_sun and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad Hbeta emission. We present here the light curves for the objects in this sample and the subsequent Hbeta time lags for the nine objects where these measurements were possible. The Hbeta lag time is directly related to the size of the broad-line region, and by combining the lag time with the measured width of the Hbeta emission line in the variable part of the spectrum, we determine the virial mass of the central supermassive black hole in these nine AGNs. The absolute calibration of the black hole masses is based on the normalization derived by Onken et al. We also examine the time lag response as a function of velocity across the Hbeta line profile for six of the AGNs. The analysis of four leads to ambiguous results with relatively flat time lags as a function of velocity. However, SBS 1116+583A exhibits a symmetric time lag response around the line center reminiscent of simple models for circularly orbiting broad-line region (BLR) clouds, and Arp 151 shows an asymmetric profile that is most easily explained by a simple gravitational infall model. Further investigation will be necessary to fully understand the constraints placed on physical models of the BLR by the velocity-resolved response in these objects.Comment: 24 pages, 16 figures and 13 tables, submitted to Ap

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

First Results from the Lick AGN Monitoring Project: The Mass of the Black Hole in Arp 151

We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 13 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7 M_sun. We present here the first results from this project -- the mass of the central black hole in Arp 151. Strong variability throughout the campaign led to an exceptionally clean Hbeta lag measurement in this object of 4.25(+0.68/-0.66) days in the observed frame. Coupled with the width of the Hbeta emission line in the variable spectrum, we determine a black hole mass of (7.1 +/- 1.2)x10^6 M_sun, assuming the Onken et al. normalization for reverberation-based virial masses. We also find velocity-resolved lag information within the Hbeta emission line which clearly shows infalling gas in the Hbeta-emitting region. Further detailed analysis may lead to a full model of the geometry and kinematics of broad line region gas around the central black hole in Arp 151.Comment: 4 pages, 4 figures and 2 tables, accepted for publication in ApJ Letter