Two chemically similar stellar overdensities on opposite sides of the plane of the Galaxy

Our Galaxy is thought to have undergone an active evolutionary history dominated by star formation, the accretion of cold gas, and, in particular, mergers up to 10 gigayear ago. The stellar halo reveals rich fossil evidence of these interactions in the form of stellar streams, substructures, and chemically distinct stellar components. The impact of dwarf galaxy mergers on the content and morphology of the Galactic disk is still being explored. Recent studies have identified kinematically distinct stellar substructures and moving groups, which may have extragalactic origin. However, there is mounting evidence that stellar overdensities at the outer disk/halo interface could have been caused by the interaction of a dwarf galaxy with the disk. Here we report detailed spectroscopic analysis of 14 stars drawn from two stellar overdensities, each lying about 5 kiloparsecs above and below the Galactic plane - locations suggestive of association with the stellar halo. However, we find that the chemical compositions of these stars are almost identical, both within and between these groups, and closely match the abundance patterns of the Milky Way disk stars. This study hence provides compelling evidence that these stars originate from the disk and the overdensities they are part of were created by tidal interactions of the disk with passing or merging dwarf galaxies.Comment: accepted for publication in Natur

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Analysis of TACI mutations in CVID & RESPI patients who have inherited HLA B*44 or HLA*B8

<p>Abstract</p> <p>Background</p> <p>Recent reports have suggested that Common Variable Immunodeficieny (CVID) can present as an autosomal dominant trait dependent on the inheritance of a set of uncommon mutations/alleles of TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) involving exons 3 or 4. Penetrance, however, appears to be incomplete. Among our clinic population, the greatest genetic linkage for CVID is to the major histocompatibility complex (MHC) on chromosome 6. The majority of our patients have inherited HLA *DQ2, *DR7, *DR3(17), *B8, and/or *B44. Of these, HLA*B44 was present in almost half of the patients and was thus the most common susceptibility allele. HLA *B44 was also found to be over-represented among patients who presented to our clinic with adult-onset recurrent sinopulmonary infections (RESPI) and normal serum immunoglobulin levels, a cohort that included first and second degree relatives of patients with CVID. One of the two original reports of the association between TACI and CVID also reported Human Leukocyte Antigen (HLA) haplotypes. Of 13 affected subjects, nine had inherited HLA *B8 and six had inherited HLA B44. This raised the possibility that TACI mutations might synergize with MHC class I alleles to enhance susceptibility to humoral immune deficiency.</p> <p>Methods</p> <p>We identified 63 CVID patients irrespective of HLA status and 13 RESPI patients who had inherited HLA*B44. To evaluate for mutations in the gene for TACI, we PCR amplified and sequenced TACI exons 3 and 4 from these patients.</p> <p>Results</p> <p>Of the 76 patients, eleven proved heterozygous for a previously reported, silent T->G polymorphism [rs35062843] at proline 97 in exon 3. However, none of the 13 RESPI patients and only one of the 63 CVID patients inherited a TACI allele previously associated with CVID. This patient was heterozygous for the TACI A181E allele (exon 4). She did not carry *DQ2, *DR7, *DR3(17), *B8, or *B44.</p> <p>Conclusion</p> <p>These findings suggest that TACI mutations are unlikely to play a critical role in creating susceptibility to CVID among patients with previously recognized MHC class I and class II susceptibility alleles.</p> <p>Supported by NIH/USIDNET N01-AI30070, NIH R21 AI079741 and NIH M01-RR00032</p

Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency

Background: Subcutaneous immunoglobulin (SCIG) therapy is an alternative to intravenous immunoglobulin (WIG) therapy.Methods: We evaluated the efficacy and safety of the SCIG Vivaglobin (R) (formerly known as Beriglobin (R) SC) under real-life conditions in a post-marketing observational study in 82 patients with primary or secondary antibody deficiencies. Health-related quality of life (HRQoL) was evaluated in a subset of 30 patients previously treated with WIG (including 11 children <14 years) using the Short Form 36 (SF-36) for patients >= 14 years of age (adults) and the Child Health Questionnaire - Parental Form 50 (CHQ-PF50) for children <14 years of age. Treatment preferences were assessed in adults.Results: The mean serum immunoglobulin G (IgG) trough level during SCIG treatment (7.5 g/L) was higher than during previous IVIG treatment (6.6 g/L; p<0.01). The investigators assessed the efficacy of SCIG therapy as "excellent" in 89% of patients. No systemic adverse drug reactions were observed. Improvements by >= 5 points were observed in 5 of 8 SF-36 subscales and in 6 of 12 CHQ-PF50 subscales. Statistically significant improvements (p <= 0.05) were observed for the SF-36 subscales of bodily pain, general health perceptions, and vitality (adults), and for the CHQ-PF50 subscales of general health perceptions, parental impact - time, parental impact - emotional, and family activities (children). Patients preferred SCIG over WIG therapy (92%) and home therapy over therapy at the clinic/physician (83%).Conclusion: This study confirms that therapy with Vivaglobin (R) at home is effective, safe, well tolerated, and improves quality of life in patients with antibody deficiency

An Exploratory Study of Primary Care Physician Decision Making Regarding Total Joint Arthroplasty

BACKGROUND: For patients to experience the benefits of total joint arthroplasty (TJA), primary care physicians (PCPs) ought to know when to refer a patient for TJA and/or optimize nonsurgical treatment options for osteoarthritis (OA). OBJECTIVE: To evaluate the ability of physicians to make clinical treatment decisions. DESIGN AND PARTICIPANTS: A survey, using ten clinical vignettes, of PCPs in Indiana. MEASUREMENTS: A test score (range 0 to 10) was computed based on the number of correct answers consistent with published explicit appropriateness criteria for TJA. We also collected demographic characteristics and physicians’ perceived success rate of TJA in terms of pain relief and functional improvement. RESULTS: There were 149 PCPs (response rate = 61%) who participated. The mean test score was 6.5 ± 1.5. Only 17% correctly identified the published success rate of TJA (i.e., ≥90%). In multivariate analysis, the only physician-related variables associated with test score were ethnicity, board status, and perceived success rate of TJA. Physicians who were white (P = .001), board-certified (P = .04), and perceived a higher success rate of TJA (P = .004) had higher test scores. CONCLUSIONS: PCP knowledge with respect to guideline-concordant care for OA could be improved, specifically in deciding when to consider TJA versus optimizing nonsurgical options. Moreover, the perception of the success rate of TJA may influence a clinician’s decision making

Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison

BACKGROUND: The Mycobacterium tuberculosis Beijing genotype is biologically different from other genotypes. We aimed to clinically and immunologically compare human tuberculosis caused by Beijing and non-Beijing strains. METHODS: Pulmonary tuberculosis patients were prospectively enrolled and grouped by their M. tuberculosis genotypes. The clinical features, plasma cytokine levels, and cytokine gene expression levels in peripheral blood mononuclear cells (PBMC) were compared between the patients in Beijing and non-Beijing groups. RESULTS: Patients in the Beijing group were characterized by significantly lower frequency of fever (odds ratio, 0.12, p = 0.008) and pulmonary cavitation (odds ratio, 0.2, p = 0.049). Night sweats were also significantly less frequent by univariate analysis, and the duration of cough prior to diagnosis was longer in Beijing compared to non-Beijing groups (medians, 60 versus 30 days, p = 0.048). The plasma and gene expression levels of interferon (IFN) γ and interleukin (IL)-18 were similar in the two groups. However, patients in the non-Beijing group had significantly increased IL-4 gene expression (p = 0.018) and lower IFN-γ : IL-4 cDNA copy number ratios (p = 0.01). CONCLUSION: Patients with tuberculosis caused by Beijing strains appear to be less symptomatic than those who have disease caused by other strains. Th1 immune responses are similar in patients infected with Beijing and non-Beijing strains, but non-Beijing strains activate more Th2 immune responses compared with Beijing strains, as evidenced by increased IL-4 expression

Elevated atmospheric CO2 and humidity delay leaf fall in Betula pendula, but not in Alnus glutinosa or Populus tremula × tremuloides

Context: Anthropogenic activity has increased the level of atmospheric CO2, which is driving an increase of global temperatures and associated changes in precipitation patterns. At Northern latitudes, one of the likely consequences of global warming is increased precipitation and air humidity. Aims: In this work, the effects of both elevated atmospheric CO2 and increased air humidity on trees commonly growing in northern European forests were assessed. Methods: The work was carried out under field conditions by using Free Air Carbon dioxide Enrichment (FACE) and Free Air Humidity Manipulation (FAHM) systems. Leaf litter fall was measured over 4 years (FACE) or 5 years (FAHM) to determine the effects of FACE and FAHM on leaf phenology. Results: Increasing air humidity delayed leaf litter fall in Betula pendula, but not in Populus tremula × tremuloides. Similarly, under elevated atmospheric CO2, leaf litter fall was delayed in Betula pendula, but not in Alnus glutinosa. Increased CO2 appeared to interact with periods of low precipitation in summer and high ozone levels during these periods to effect leaf fall. Conclusions: This work shows that increased CO2 and humidity delay leaf fall, but this effect is species specific

Genetic Association Study of Common Mitochondrial Variants on Body Fat Mass

Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94×10-3 and 4.58×10-2, respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β) was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31×10-3) and body fat mass (adjusted P = 5.67×10-4) Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism

Ginseng and Ganoderma lucidum Use after Breast Cancer Diagnosis and Quality of Life: A Report from the Shanghai Breast Cancer Survival Study

Objective: To evaluate associations between quality of life (QOL) and use of ginseng and Ganoderma lucidum (G. lucidum) among breast cancer survivors. Methods: Included in this study were 4,149 women with breast cancer who participated in the Shanghai Breast Cancer Survival Study. Ginseng use was assessed at 6-, 18-, and 36-month post-diagnosis surveys; G. lucidum use was assessed at the 6- and 36-month surveys. QOL was evaluated at the 6- and 36-month surveys. Multiple linear regression models were used to examine associations between ginseng and G.lucidum use and QOL assessed at the 36-month survey, with adjustment for potential confounders and baseline QOL. Results: At 6 months post-diagnosis, 14.2 % of participants reported regular use of ginseng and 58.8 % reported use of G. lucidum. We found no significant associations between ginseng use at 6, 18, and 36 months post-diagnosis and participants’ total QOL score or individual scores for psychological, physical, or social well-being. Post-diagnosis G. lucidum use was positively associated with social well-being (adjusted mean difference: 1.26; 95 % CI: 0.66, 1.86), but was inversely associated with physical well-being (adjusted mean difference: 21.16; 95 % CI: 21.86, 20.47) with a dose-response pattern observed for cumulative number of times of use (P for trend,0.001 for both). Conclusion: We found no evidence that post-diagnosis ginseng use improved the QOL of breast cancer survivors. Post

MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults.</p> <p>Methods</p> <p>A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks.</p> <p>Results</p> <p>After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (<it>P </it>< 0.05 for either of these genotypes) and TT genotype in the high FA group (<it>P </it>< 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, <it>P </it>= 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, <it>P </it>= 0.989).</p> <p>Conclusions</p> <p>This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.</p