The presence and predictors of complicated grief symptoms in perinatally-bereaved mothers from a bereavement support organization

The present study investigated the presence and possible predictors of complicated grief symptoms in perinatally-bereaved mothers (N = 121) up to 5 years post-bereavement. The presence of complicated grief scores in the clinical range was 12.4%, which is higher than in many other bereaved populations, and the presence of other living children may protect against the development of complicated grief symptoms. The majority of the women were able to negotiate a perinatal loss without developing complicated grief; however, there remains an important group of women who up to 5 years later score in the clinical range for complicated grief symptoms

High-precision multi-band measurements of the angular clustering of X-ray sources

In this paper we present the two-point angular correlation function of the X-ray source population of 1063 XMM-Newton observations at high Galactic latitudes, comprising up to ~30000 sources over a sky area of 125.5 sq. deg, in three energy bands: 0.5-2 (soft), 2-10 (hard), and 4.5-10 (ultrahard) keV. We have measured the angular clustering of our survey and find significant positive clustering signals in the soft and hard bands, and a marginal clustering detection in the ultrahard band. We find dependency of the clustering strength on the flux limit and no significant differences in the clustering properties between sources with high hardness ratios and those with low hardness ratios. Our results show that obscured and unobscured objects share similar clustering properties and therefore they both reside in similar environments, in agreement with the unified model of AGN. We deprojected the angular clustering parameters via Limber's equation to compute their typical spatial lengths. From that we have inferred the typical mass of the dark matter haloes in which AGN at redshifts of ~1 are embedded. The short AGN lifetimes derived suggest that AGN activity might be a transient phase that can be experienced several times by a large fraction of galaxies throughout their lives.Comment: 14 pages, 9 figures, accepted for publication in Astronomy and Astrophysic

Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report

Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance

Moclobemide excretion in human breast milk

1 Six lactating white women, aged 24-36 years, received a single oral dose of 300 mg moclobemide, between 09.00 h and 11.00 h, 3 to 5 days after the delivery of a full term neonate. 2 Complete milk collections were obtained before, 3, 6, 9, 12 and 24 h after drug administration by means of a breast pump. Venous blood samples were drawn before, and 0.5, 1, 3, 4.5, 6, 9, 12, 24 h post-dosing. 3 Moclobemide, and its major metabolite (Ro 12-8095) were measured in milk and plasma samples using h.p.l.c. The active metabolite (Ro 12-5637) could only be detected in plasma. 4 Moclobemide and its metabolites were not detectable in 24 h plasma samples. Cmax, tmax and t½h for moclobemide were (mean ± s.d.) 2.70 ± 1.24 mg l-1, 2.03 ± 1.19 h and 2.26 ± 0.26 h, respectively. 5 The concentrations of moclobemide and Ro 12-8095 in milk were highest at 3 h after drug administration and the drug and metabolite were not detectable after 12 h. Ro 12-5637 was not detected in any milk sample. The percentages of the dose excreted as moclobemide and Ro 12-8095 were (mean ± s.d.) 0.057 ± 0.020% and 0.031 ± 0.011%, respectively. An average 3.5 kg breast-fed neonate would therefore be exposed to only a 0.05 mg kgmoclobemide dose (approximately 1% of the maternal dose on the mg kg-' basis)

HIV/AIDS Drugs for Sub-Saharan Africa: How Do Brand and Generic Supply Compare?

BACKGROUND: Significant quantities of antiretroviral drugs (ARVs) to treat HIV/AIDS have been procured for Sub-Saharan Africa for the first time in their 20-year history. This presents a novel opportunity to empirically study the roles of brand and generic suppliers in providing access to ARVs. METHODOLOGY/PRINCIPAL FINDINGS: An observational study of brand and generic supply based on a dataset of 2,162 orders of AIDS drugs for Sub-Saharan Africa reported to the Global Price Reporting Mechanism at the World Health Organization from January 2004-March 2006 was performed. Generic companies supplied 63% of the drugs studied, at prices that were on average about a third of the prices charged by brand companies. 96% of the procurement was of first line drugs, which were provided mostly by generic firms, while the remaining 4%, of second line drugs, was sourced primarily from brand companies. 85% of the generic drugs in the sample were manufactured in India, where the majority of the drugs procured were ineligible for patent protection. The remaining 15% was manufactured in South Africa, mostly under voluntary licenses provided by brand companies to a single generic company. In Sub-Saharan African countries, four first line drugs in the dataset were widely patented, however no general deterrent to generic purchasing based on a patent was detected. CONCLUSIONS/SIGNIFICANCE: Generic and brand companies have played distinct roles in increasing the availability of ARVs in Sub-Saharan Africa. Generic companies provided most of the drugs studied, at prices below those charged by brand companies, and until now, almost exclusively supplied several fixed-dose combination drugs. Brand companies have supplied almost all second line drugs, signed voluntary licenses with generic companies, and are not strictly enforcing patents in certain countries. Further investigation into how price reductions in second line drugs can be achieved and the cheapest drugs can actually be procured is warranted

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Fossil Groups Origins: I. RX J105453.3+552102 a very massive and relaxed system at z~0.5

The most accepted scenario for the origin of fossil groups (FGs) is that they are galaxy associations in which the merging rate was fast and efficient. These systems have assembled half of their mass at early epoch of the Universe, subsequently growing by minor mergers. They could contain a fossil record of the galaxy structure formation. We have started a project in order to characterize a large sample of FGs. In this paper we present the analysis of the fossil system RX J105453.3+552102. Optical deep images were used for studying the properties of the brightest group galaxy and for computing the photometric luminosity function of the group. We have also performed a detail dynamical analysis of the system based on redshift data for 116 galaxies. This galaxy system is located at z=0.47, and shows a quite large line-of-sight velocity dispersion \sigma_{v}~1000 km/s. Assuming the dynamical equilibrium, we estimated a virial mass of M ~ 10^{15} h_{70} M_{\odot}. No evidence of substructure was found within 1.4 Mpc radius. We found a statistically significant departure from Gaussianity of the group members velocities in the most external regions of the group. This could indicate the presence of galaxies in radial orbits in the external region of the group. We also found that the photometrical luminosity function is bimodal, showing a lack of M_{r} ~ -19.5 galaxies. The brightest group galaxy shows low Sersic parameter (n~2) and a small peculiar velocity. Indeed, our accurate photometry shows that the difference between the brightest and the second brightest galaxies is 1.9 mag in the r-band, while the classical definition of FGs is based on a magnitude gap of 2. We conclude that this fossil system does not follow the empirical definition of FGs. Nevertheless, it is a massive, old and undisturbed galaxy system with little infall of L^{*} galaxies since its initial collapse.Comment: 17 pages, 14 figures, accepted for publication at A&

Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation

The nasopharyngeal commensal bacteria Streptococcus pneumoniae is also a frequent cause of serious infections. Nasopharyngeal colonisation with S. pneumoniae inhibits subsequent re-colonisation by inducing Th17-cell adaptive responses, whereas vaccination prevents invasive infections by inducing antibodies to S. pneumoniae capsular polysaccharides. In contrast, protection against invasive infection after nasopharyngeal colonisation with mutant S. pneumoniae strains was associated with antibody responses to protein antigens. The role of colonisation-induced Th17-cell responses during subsequent invasive infections is unknown. Using mouse models, we show that previous colonisation with S. pneumoniae protects against subsequent lethal pneumonia mainly by preventing bacteraemia with a more modest effect on local control of infection within the lung. Previous colonisation resulted in CD4-dependent increased levels of Th17-cell cytokines during subsequent infectious challenge. However, mice depleted of CD4 cells prior to challenge remained protected against bacteraemia, whereas no protection was seen in antibody deficient mice and similar protection could be achieved through passive transfer of serum. Serum from colonised mice but not antibody deficient mice promoted phagocytosis of S. pneumoniae, and previously colonised mice were able to rapidly clear S. pneumoniae from the blood after intravenous inoculation. Thus, despite priming for a Th17-cell response during subsequent infection, the protective effects of prior colonisation in this model was not dependent on CD4 cells but on rapid clearance of bacteria from the blood by antibody-mediated phagocytosis. These data suggest that whilst nasopharyngeal colonisation induces a range of immune responses, the effective protective responses depend upon the site of subsequent infectio

Ammonium regeneration: Its contribution to phytoplankton nitrogen requirements in a eutrophic environment

Ammonium regeneration, nutrient uptake, bacterial activity and primary production were measured from March to August 1980 in Bedford Basin, Nova Scotia, Canada, a eutrophic environment. Rates of regeneration and nutrient uptake were determined using 15N isotope dilution and tracer methodology. Although primary production, nutrient uptake and ammonium regeneration were significantly intercorrelated, no relationship was detected between these parameters and heterotrophic activity. The average contribution of ammonium to total nitrogen (ammonium+nitrate) uptake was similar in the spring and in the summer (approximately 60%). On a seasonal average basis, 36% of the phytoplankton ammonium uptake could be supplied by rapid remineralization processes. In spite of the high average contribution of NH4 regeneration to phytoplankton ammonia uptake, there is indirect evidence suggesting that other NH4 sources may occasionally be important