Systematic uncertainties in the determination of the local dark matter density

A precise determination of the local dark matter density and an accurate control over the corresponding uncertainties are of paramount importance for Dark Matter (DM) searches. Using very recent high-resolution numerical simulations of a Milky Way like object, we study the systematic uncertainties that affect the determination of the local dark matter density based on dynamical measurements in the Galaxy. In particular, extracting from the simulation with baryons the orientation of the Galactic stellar disk with respect to the DM distribution, we study the DM density for an observer located at $\sim$8 kpc from the Galactic center {\it on the stellar disk}, $\rho_0$. This quantity is found to be always larger than the average density in a spherical shell of same radius $\bar{\rho}_0$, which is the quantity inferred from dynamical measurements in the Galaxy, and to vary in the range $\rho_0/\bar{\rho}_0=1.01-1.41$. This suggests that the actual dark matter density in the solar neighbourhood is on average 21\% larger than the value inferred from most dynamical measurements, and that the associated systematic errors are larger than the statistical errors recently discussed in the literature.Comment: 6 pages, 3 figures, matches published versio

Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to he activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism

A new parenting-based group intervention for young anxious children: results of a randomized controlled trial

Objective Despite recent advances, there are still no interventions that have been developed for the specific treatment of young children who have anxiety disorders. This study examined the impact of a new, cognitive–behaviorally based parenting intervention on anxiety symptoms. Method Families of 74 anxious children (aged 9 years or less) took part in a randomized controlled trial, which compared the new 10-session, group-format intervention with a wait-list control condition. Outcome measures included blinded diagnostic interview and self-reports from parents and children. Results Intention-to-treat analyses indicated that children whose parent(s) received the intervention were significantly less anxious at the end of the study than those in the control condition. Specifically, 57% of those receiving the new intervention were free of their primary disorder, compared with 15% in the control condition. Moreover, 32% of treated children were free of any anxiety diagnosis at the end of the treatment period, compared with 6% of those in the control group. Treatment gains were maintained at 12-month follow-up. Conclusions This new parenting-based intervention may represent an advance in the treatment of this previously neglected group. Clinical trial registration information: Anxiety in Young Children: A Randomized Controlled Trial of a New Cognitive-Behaviourally Based Parenting Intervention; http://www.isrctn.org/; ISRCTN12166762

A note on organizational structure and environmental liability

This paper employs a multi-task principal-agent model to examine how a corporation’s organizational structure and liability rules for environmental damages affect the incentive schemes offered to managers. We derive environmental liability rules for risk averse managers under two alternative organizational structures: a product-based organization (PBO) and functional-based organization (FBO). For a PBO, it is shown that efficiency is independent of whether the firm or managers are liable for environmental damages; in a FBO it is optimal either to hold the firm liable for environmental damages or, equivalently, to only hold the environmental managers liable for damages. It is also shown that the two organizational structures are equally efficient when there is no correlation between environmental damages from products and no spillover between managerial effort across products or functions. Numerical results further reveal that beneficial spillovers between functions for the same product favours a PBO over a FBO; beneficial spillovers across functions favours a FBO

Diagnosing Severe Falciparum Malaria in Parasitaemic African Children: A Prospective Evaluation of Plasma PfHRP2 Measurement.

In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10) plasma PfHRP2 and risk of death. Mortality increased 20% per log(10) increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children

A common genetic target for environmental and heritable influences on aggressiveness in Drosophila

Environmental and genetic factors can modulate aggressiveness, but the biological mechanisms underlying their influence are largely unknown. Social experience with conspecifics suppresses aggressiveness in both vertebrate and invertebrate species, including Drosophila. We searched for genes whose expression levels correlate with the influence of social experience on aggressiveness in Drosophila by performing microarray analysis of head tissue from socially isolated (aggressive) vs. socially experienced (nonaggressive) male flies. Among {approx}200 differentially expressed genes, only one was also present in a gene set previously identified by profiling Drosophila strains subjected to genetic selection for differences in aggressiveness [Dierick HA, Greenspan RJ (2006) Nat Genet 38:1023–1031]. This gene, Cyp6a20, encodes a cytochrome P450. Social experience increased Cyp6a20 expression and decreased aggressiveness in a reversible manner. In Cyp6a20 mutants, aggressiveness was increased in group-housed but not socially isolated flies. These data identify a common genetic target for environmental and heritable influences on aggressiveness. Cyp6a20 is expressed in a subset of nonneuronal support cells associated with pheromone-sensing olfactory sensilla, suggesting that social experience may influence aggressiveness by regulating pheromone sensitivity

Cyclin D2-knock-out mice with attenuated dentate gyrus neurogenesis have robust deficits in long-term memory formation.

Neurobehavioral studies have produced contradictory findings concerning the function of neurogenesis in the adult dentate gyrus. Previous studies have proved inconsistent across several behavioral endpoints thought to be dependent on dentate neurogenesis, including memory acquisition, short-term and long-term retention of memory, pattern separation, and reversal learning. We hypothesized that the main function of dentate neurogenesis is long-term memory formation because we assumed that a newly formed and integrated neuron would have a long-term impact on the local neural network. We used a cyclin D2-knock-out (cyclin D2-/-) mouse model of endogenously deficient dentate neurogenesis to test this hypothesis. We found that cyclin D2-/- mice had robust and sustained loss of long-term memory in two separate behavioral tasks, Morris water maze (MWM) and touchscreen intermediate pattern separation. Moreover, after adjusting for differences in brain volumes determined by magnetic resonance (MR) imaging, reduced dentate neurogenesis moderately correlated with deficits in memory retention after 24 hours. Importantly, cyclin D2-/- mice did not show deficits in learning acquisition in a touchscreen paradigm of intermediate pattern separation or MWM platform location, indicating intact short-term memory. Further evaluation of cyclin D2-/- mice is necessary to confirm that deficits are specifically linked to dentate gyrus neurogenesis since cyclin D2-/- mice also have a reduced size of the olfactory bulb, hippocampus, cerebellum and cortex besides reduced dentate gyrus neurogenesis

A Strategy to Optimize Recovery in Orthopedic Sports Injuries

An important goal for treatment of sports injuries is to have as short a recovery time as possible. The critical problem with current orthopedic implants is that they are designed to be permanent and have a high complication rate (15%) that often requires removal and replacement with a second surgery; and subsequently a second rehabilitation cycle. This study was designed to test the feasibility of having a device that could provide the needed mechanical properties, while promoting healing, for a specified amount of time and then degrade away, to shorten the recovery time. The specific strategy was to create a surface layer on a degradable metal alloy with a controllable degradation rate. Previous studies have shown the feasibility of using surface treatments to alter the surface integrity (i.e., topography, microhardness, and residual stress) leading to increased fatigue strength and a decreased degradation rate. This study was an extension of these previous studies to look at the changes in surface integrity and mechanical properties initially as well as the degradation over time for two surface treatments (shot peening and burnishing). Although the treatments improved initial properties and the burnishing treatment slowed degradation rate, the faster degradation of the base material in vitro (compared to previous studies) probably reduced the overall impact. Therefore although the study helped support the feasibility of this approach by showing the ability of the surface treatment to modify surface integrity, initial mechanical properties, and degradation rate; the degradation rate of the base material used needs to be slower and/or the surface treatment needs to create a bigger change in the degradation rate. Further it ultimately needs to be shown that the surface treatment can produce a material that will allow orthopedic devices to meet the required clinical design constraints in vivo

HST/NICMOS observations of the GLIMPSE9 stellar cluster

We present HST/NICMOS photometry, and low-resolution K-band spectra of the GLIMPSE9 stellar cluster. The newly obtained color-magnitude diagram shows a cluster sequence with H-Ks =1 mag, indicating an interstellar extinction Aks=1.6\pm0.2 mag. The spectra of the three brightest stars show deep CO band-heads, which indicate red supergiants with spectral type M1-M2. Two 09-B2 supergiants are also identified, which yield a spectrophotometric distance of 4.2\pm0.4 kpc. Presuming that the population is coeval, we derive an age between 15 and 27 Myr, and a total cluster mass of 1600\pm400 Msun, integrated down to 1 Msun. In the vicinity of GLIMPSE9 are several HII regions and SNRs, all of which (including GLIMPSE 9) are probably associated with a giant molecular cloud (GMC) in the inner galaxy. GLIMPSE9 probably represents one episode of massive star formation in this GMC. We have identified several other candidate stellar clusters of the same complex.Comment: 13 pages, 14 figures. accepted for publication in ApJ. A version with high-resolution figures can be found at the following location ftp://ftp.rssd.esa.int/pub/mmessine/ms.pdf New version with updated reference