The relationship between FV Leiden and pulmonary embolism

Pulmonary embolism (PE) is one of the leading causes of in-patient hospital deaths. As a consequence, the identification of hemostatic variables that could identify those at risk would be important in reducing mortality. It has previously been thought that deep vein thrombosis and PE are a single disease entity and would, therefore, have the same risk factors. This view is changing, however, with the realization that the prevalence of FV Leiden, a recognized genetic risk factor for deep vein thrombosis, may be a 'milder' genetic risk factor for PE. These observations suggest that PE is not only associated with a different set of risk factors, but may be reflective of a different clot structure

Pierre Auger Data, Photons, and Top-Down Cosmic Ray Models

We consider the ultra-high energy cosmic ray (UHECR) spectrum as measured by the Pierre Auger Observatory. Top-down models for the origin of UHECRs predict an increasing photon component at energies above about $10^{19.7}$eV. Here we present a simple prescription to compare the Auger data with a prediction assuming a pure proton component or a prediction assuming a changing primary component appropriate for a top-down model. We find that the UHECR spectrum predicted in top-down models is a good fit to the Auger data. Eventually, Auger will measure a composition-independent spectrum and will be capable of either confirming or excluding the quantity of photons predicted in top-down models.Comment: 8 pages, 3 figure

The appeal of the Functional Fitness MOT to older adults and health professionals in an outpatient setting: a mixed-method feasibility study

Purpose: To understand the views and perceptions regarding the Functional Fitness MOT (FFMOT), a battery of functional tests followed by a brief motivational interview, of both the older people undergoing it and the health professionals delivering it. Patients and methods: Physically inactive older adults (n=29) underwent the FFMOT and subsequently attended focus groups to share their perceptions of it and to discuss the barriers, motivators, health behavior change, and scope to improve physical activity (PA) levels. PA levels were recorded at baseline and again at 12 weeks together with a post-intervention questionnaire concerning behavior change. Participating physiotherapists and technical instructors were interviewed. Results: Most participants felt they had learned about their abilities and comparisons with their peers, had a change in perception about the importance of good balance and strength, and felt the FFMOT helped raise their awareness of local and self-directed physical activity opportunities. Most felt their awareness of the need for PA had not changed, but 25% of participants started a new organized PA opportunity. The health professionals perceived the FFMOT as being easy to administer, educating, and motivating for participants to increase their PA. Space, time, finances, and insecurity about having the necessary skills to conduct the FFMOTs were seen as barriers in implementing the FFMOT in daily practice. Conclusion: Over half of those offered the FFMOT accepted it, suggesting it is appealing. However, most participants felt they were already active enough and that their awareness of the need for PA had not changed. There were positive perceptions of the FFMOT from both professionals and older people, but both felt the FFMOT could be held in a community venue. The overall findings suggest that the FFMOT is feasible in the clinical setting, but its effectiveness has yet to be determined

Behavioral Risk Elicits Selective Activation of the Executive System in Adolescents: Clinical Implications

We investigated adolescent brain processing of decisions under conditions of varying risk, reward, and uncertainty. Adolescents (n = 31) preformed a Decision–Reward Uncertainty task that separates decision uncertainty into behavioral and reward risk, while they were scanned using functional magnetic resonance imaging. Behavioral risk trials involved uncertainty about which action to perform to earn a fixed monetary reward. In contrast, during reward risk the decision that might lead to a reward was known, but the likelihood of earning a reward was probabilistically determined. Behavioral risk trials evoked greater activation than the reward risk and no risk conditions in the anterior cingulate, medial frontal gyrus, bilateral frontal poles, bilateral inferior parietal lobe, precuneus, bilateral superior-middle frontal gyrus, inferior frontal gyrus, and insula. Our results were similar to those of young adults using the same task (Huettel, 2006) except that adolescents did not show significant activation in the posterior supramarginal gyrus during behavioral risk. During the behavioral risk condition regardless of reward outcome, overall mean frontal pole activity showed a positive correlation with age during the behavioral and reward risk conditions suggesting a developmental difference of this region of interest. Additionally, reward response to the Decision–Reward Uncertainty task in adolescents was similar to that seen in young adults (Huettel, 2006). Our data did not show a correlation between age and mean ventral striatum activity during the three conditions. While our results came from a healthy high functioning non-maltreated sample of adolescents, this method can be used to address types of risks and reward processing in children and adolescents with predisposing vulnerabilities and add to the paucity of imaging studies of risk and reward processing during adolescence

Two photon annihilation of Kaluza-Klein dark matter

We investigate the fermionic one-loop cross section for the two photon annihilation of Kaluza-Klein (KK) dark matter particles in a model of universal extra dimensions (UED). This process gives a nearly mono-energetic gamma-ray line with energy equal to the KK dark matter particle mass. We find that the cross section is large enough that if a continuum signature is detected, the energy distribution of gamma-rays should end at the particle mass with a peak that is visible for an energy resolution of the detector at the percent level. This would give an unmistakable signature of a dark matter origin of the gamma-rays, and a unique determination of the dark matter particle mass, which in the case studied should be around 800 GeV. Unlike the situation for supersymmetric models where the two-gamma peak may or may not be visible depending on parameters, this feature seems to be quite robust in UED models, and should be similar in other models where annihilation into fermions is not helicity suppressed. The observability of the signal still depends on largely unknown astrophysical parameters related to the structure of the dark matter halo. If the dark matter near the galactic center is adiabatically contracted by the central star cluster, or if the dark matter halo has substructure surviving tidal effects, prospects for detection look promising.Comment: 17 pages, 3 figures; slightly revised versio

New spectra in the HEIDI Higgs models

We study the so-called HEIDI models, which are renormalizable extensions of the standard model with a higher dimensional scalar singlet field. As an additional parameter we consider a higher-dimensional mixing mass parameter. This leads to enriched possibilities compared to a previous study. We find effective spectral densities of the Higgs propagator, consisting of one, two or no particle peaks, together with a continuum. We compare with the LEP-2 data and determine for which range of the model parameters the data can be described. Assuming two peaks to be present we find for the new mass scale \nu\approx 56\pm12 \gev, largely independent of the dimension. In the limiting case of $d\rightarrow 6$ and two peaks we find a higher dimensional coupling constant $\alpha_6=0.70 \pm 0.18$, indicative of strong interactions among the higher dimensional fields. The LHC will not be able to study this Higgs field.Comment: 17 pages, 4 figure

Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis.

Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis

Astrophysical Uncertainties in the Cosmic Ray Electron and Positron Spectrum From Annihilating Dark Matter

In recent years, a number of experiments have been conducted with the goal of studying cosmic rays at GeV to TeV energies. This is a particularly interesting regime from the perspective of indirect dark matter detection. To draw reliable conclusions regarding dark matter from cosmic ray measurements, however, it is important to first understand the propagation of cosmic rays through the magnetic and radiation fields of the Milky Way. In this paper, we constrain the characteristics of the cosmic ray propagation model through comparison with observational inputs, including recent data from the CREAM experiment, and use these constraints to estimate the corresponding uncertainties in the spectrum of cosmic ray electrons and positrons from dark matter particles annihilating in the halo of the Milky Way.Comment: 21 pages, 9 figure

Neural mechanisms of risky decision-making and reward response in adolescent onset cannabis use disorder

Background—Neural mechanisms of decision-making and reward response in adolescent cannabis use disorder (CUD) are underexplored. Methods—Three groups of male adolescents were studied: CUD in full remission (n=15); controls with psychopathology without substance use disorder history(n=23); and healthy controls(n=18). We investigated neural processing of decision-making and reward under conditions of varying risk and uncertainty with the Decision-Reward Uncertainty Task while participants were scanned using functional magnetic resonance imaging. Results—Abstinent adolescents with CUD compared to controls with psychopathology showed hyperactivation in one cluster that spanned left superior parietal lobule/left lateral occipital cortex/precuneus while making risky decisions that involved uncertainty, and hypoactivation in left orbitofrontal cortex to rewarded outcomes compared to no-reward after making risky decisions. Post-hoc region of interest analyses revealed that both control groups significantly differed from the CUD group (but not from each other) during both the decision-making and reward outcome phase of the Decision-Reward Uncertainty Task. In the CUD group, orbitofrontal activations to reward significantly and negatively correlated with total number of individual drug classes the CUD patients experimented with prior to treatment. CUD duration significantly and negatively correlated with orbitofrontal activations to no-reward. Conclusions—The adolescent CUD group demonstrated distinctly different activation patterns during risky decision-making and reward processing (after risky decision-making) compared to both the controls with psychopathology and healthy control groups. These findings suggest that neural differences in risky decision-making and reward processes are present in adolescent addiction, persist after remission from first CUD treatment, and may contribute to vulnerability for adolescent addiction

Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis

Background The Ebola virus disease outbreak that started in Western Africa in 2013 was unprecedented because it spread within densely populated urban environments and affected many thousands of people. As a result, previous advice and guidelines need to be critically reviewed, especially with regard to transmission risks in different contexts. Methods Scientific and grey literature were searched for articles about any African filovirus. Articles were screened for information about transmission (prevalence or odds ratios especially). Data were extracted from eligible articles and summarised narratively with partial meta-analysis. Study quality was also evaluated. Results 31 reports were selected from 6552 found in the initial search. Eight papers gave numerical odds for contracting filovirus illness, 23 further articles provided supporting anecdotal observations about how transmission probably occurred for individuals. Many forms of contact (conversation, sharing a meal, sharing a bed, direct or indirect touching) were unlikely to result in disease transmission during incubation or early illness. Amongst household contacts who reported directly touching a case, the attack rate was 32% (95% CI 26-38%). Risk of disease transmission between household members without direct contact was low (1%; 95% CI 0-5%). Caring for a case in the community, especially until death, and participation in traditional funeral rites were strongly associated with acquiring disease, probably due to a high degree of direct physical contact with case or cadaver. Conclusions Transmission of filovirus is unlikely except through close contact, especially during the most severe stages of acute illness. More data are needed about the context, intimacy and timing of contact required to raise the odds of disease transmission. Risk factors specific to urban settings may need to be determined