ABSTRACT
Dark matter may be detected in X-ray decay, including from the decay of the dark matter particles that make up the Milky Way (MW) halo. We use a range of density profiles to compute X-ray ...line intensity profiles, with a focus on the resonantly produced sterile neutrino dark matter candidate. Compared to the Navarro–Frenk–White density profile, we show that using an adiabatically contracted halo profile suppresses the line intensity in the halo outskirts and enhances it in the Galactic Centre (GC), although this enhancement is eliminated by the likely presence of a core within 3 kpc. Comparing our results to MW halo observations, other X-ray observations, and structure formation constraints implies a sterile neutrino mixing angle parameter s11 ≡ sin 2(2θ) × 1011 ∼ 3, 4 (particle lifetime $\tau _{28}\equiv \tau /(10^{28}\rm {s})\sim 1.0,1.3$), which is nevertheless is strong tension with some reported non-detections. We make predictions for the likely decay flux that the X-Ray Imaging and Spectroscopy Mission (XRISM) satellite would measure in the GC, plus the Virgo and Perseus clusters, and outline further steps to determine whether the dark matter is indeed resonantly produced sterile neutrinos as detected in X-ray decay.
ABSTRACT The claimed detection of large amounts of substructure in lensing flux anomalies, and in Milky Way stellar stream gap statistics, has led to a step change in constraints on simple warm dark ...matter models. In this study, we compute predictions for the halo mass function both for these simple models and for comprehensive particle physics models of sterile neutrinos and dark acoustic oscillations. We show that the mass function fit of Lovell et al. underestimates the number of haloes less massive than the half-mode mass, $M_\mathrm {hm}$, by a factor of 2, relative to the extended Press–Schechter (EPS) method. The alternative approach of applying EPS to the Viel et al. matter power spectrum fit instead suggests good agreement at $M_\mathrm {hm}$ relative to the comprehensive model matter power spectrum results, although the number of haloes with mass $\rm{\lt} M_\mathrm {hm}$ is still suppressed due to the absence of small-scale power in the fitting function. Overall, we find that the number of dark matter haloes with masses $\rm{\lt} 10^{8}{\, \rm M_\odot }$ predicted by competitive particle physics models is underestimated by a factor of ∼2 when applying popular fitting functions, although careful studies that follow the stripping and destruction of subhaloes will be required in order to draw robust conclusions.
Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global ...prevalence and risk factors.
MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated.
Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data.
The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described.
Irritable bowel syndrome (IBS) is thought to be commoner in women. However, no systematic review has confirmed whether this is the case, or assessed whether any proposed female preponderance remains ...stable according to geography and criteria used to define IBS. Nor has effect of gender on subtype of IBS been examined systematically.
MEDLINE, EMBASE, and EMBASE Classic were searched (up to October 2011) to identify population-based studies reporting prevalence of IBS in adults (≥15 years) according to gender, and defined using symptom-based criteria, or questionnaire. The prevalence of IBS in women and men was extracted for all studies, and according to study location and diagnostic criteria used, and compared using odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence of each subtype of IBS, according to predominant stool pattern, was compared in women and men with IBS.
Of the 390 papers evaluated, 56 studies containing 188,229 subjects were eligible. The OR for IBS in women, compared with men, in all studies was 1.67 (95% CI: 1.53-1.82). Prevalence of IBS was not significantly higher in women, compared with men, in South Asian, South American, or African studies. The OR was highest with the Rome I criteria (1.99; 95% CI: 1.76-2.25), and lowest with the Rome II criteria (1.40; 95% CI: 1.24-1.59). Women with IBS were more likely to exhibit the constipation-predominant subtype (OR: 2.38; 95% CI: 1.45-3.92), and less likely to meet criteria for the diarrhea-predominant subtype (OR: 0.45; 95% CI: 0.32-0.65) than men with IBS.
Prevalence of IBS appeared modestly higher in women, and this remained relatively stable according to geography and criteria used to define its presence. However, among individuals with IBS, subtypes varied according to gender.
Biased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a ...series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinociception therapeutic window in a series of compounds spanning a wide range of signaling bias. We find that βarrestin-biased compounds, such as fentanyl, are more likely to induce respiratory suppression at weak analgesic doses, while G protein signaling bias broadens the therapeutic window, allowing for antinociception in the absence of respiratory suppression.
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•Mu opioid agonists were made to promote signaling through G proteins or βarrestin2•Potency was determined for pain relief and respiratory depression in mice•Fentanyl’s narrow safety window correlates with its preference for βarrestin2•Increasing signaling through G proteins directly improves the therapeutic index
Exploiting ligand bias enables the design of new opioid receptor ligands aimed at reducing side effects.
•5hmC is more pronounced in nDNA than mtDNA or RNA.•Levels of 5mC and 5hmC are increased in PCAD and LAD HPG compared to NC HPG.•Levels of 5fC and 5caC are decreased in PCAD and LAD HPG compared to ...NC HPG.•Levels of TET1 are increased in PCAD and LAD HPG compared to NC HPG.
The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p<0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p<0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.
Increasing evidence suggests that oxidative stress is associated with normal aging and several neurodegenerative diseases, including Alzheimer's disease (AD). Here we quantified multiple oxidized ...bases in nuclear and mitochondrial DNA of frontal, parietal, and temporal lobes and cerebellum from short postmortem interval AD brain and age‐matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring (GC/MS‐SIM) and stable labeled internal standards. Nuclear and mitochondrial DNA were extracted from eight AD and eight age‐matched control subjects. We found that levels of multiple oxidized bases in AD brain specimens were significantly (p < 0.05) higher in frontal, parietal, and temporal lobes compared to control subjects and that mitochondrial DNA had approximately 10‐fold higher levels of oxidized bases than nuclear DNA. These data are consistent with higher levels of oxidative stress in mitochondria. Eight‐hydroxyguanine, a widely studied biomarker of DNA damage, was approximately 10‐fold higher than other oxidized base adducts in both AD and control subjects. DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was only slightly affected in AD brains. These results suggest that oxidative damage to mitochondrial DNA may contribute to the neurodegeneration of AD.
This paper focuses on the relatively late emergence of psychiatric epidemiology as an international discipline, through local-global exchanges during the first 15 years of the World Health ...Organization (WHO). Building an epidemiological canon within WHO's Mental Health Programme faced numerous obstacles. First, an idealist notion of mental health inherent in WHO's own definition of health contributed to tensions around the object of psychiatric epidemiology. Second, the transfer of methods from medical epidemiology to research on mental disorders required mobilizing conceptual justifications, including a 'contagion argument'. Third, epidemiological research at WHO was stymied by other public health needs, resource scarcity and cultural barriers. This history partly recapitulates the development of psychiatric epidemiology in North America and Europe, but is also shaped by concerns in the developing world, translated through first-world 'experts'. Resolving the tensions arising from these obstacles allowed WHO to establish its international schizophrenia research, which in turn provided proof of concept for psychiatric epidemiology in the place of scepticism within and without psychiatry.
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