Stellar Collisions and Ultracompact X-ray Binary Formation

(abridged) We report the results of SPH calculations of parabolic collisions between a subgiant or slightly evolved red-giant star and a neutron star (NS). Such collisions are likely to form ultracompact X-ray binaries (UCXBs) observed today in old globular clusters. In particular, we compute collisions of a 1.4 Msun NS with realistically modelled parent stars of initial masses 0.8 and 0.9 Msun, each at three different evolutionary stages (corresponding to three different radii R). The distance of closest approach for the initial orbit varies from 0.04 R (nearly head-on) to 1.3 R (grazing). These collisions lead to the formation of a tight binary, composed of the NS and the subgiant or red-giant core, embedded in an extremely diffuse common envelope (CE) typically of mass ~0.1 to 0.3 Msun. Our calculations follow the binary for many hundreds of orbits, ensuring that the orbital parameters we determine at the end of the calculations are close to final. Some of the fluid initially in the envelope of the (sub)giant, from 0.003 to 0.023 Msun in the cases we considered, is left bound to the NS. The eccentricities of the resulting binaries range from about 0.2 for our most grazing collision to about 0.9 for the nearly head-on cases. In almost all the cases we consider, gravitational radiation alone will cause sufficiently fast orbital decay to form a UCXB within a Hubble time, and often on a much shorter timescale. Our hydrodynamics code implements the recent SPH equations of motion derived with a variational approach by Springel & Hernquist and by Monaghan. Numerical noise is reduced by enforcing an analytic constraint equation that relates the smoothing lengths and densities of SPH particles. We present tests of these new methods to help demonstrate their improved accuracy.Comment: 41 pages, 17 figures, accepted by Ap

Cis-Acting Regulation of Brain-Specific ANK3 Gene Expression by a Genetic Variant Associated with Bipolar Disorder

Several genome-wide association studies (GWAS) for bipolar disorder (BD) have found a strong association of the Ankyrin3 (ANK3) gene. This association spans numerous linked single nucleotide polymorphisms (SNPs) in a ~250 kb genomic region overlapping ANK3. The associated region encompasses predicted regulatory elements as well as two of six validated alternative first exons, which encode distinct protein domains at the N-terminus of the protein also known as ankyrin-G (AnkG). Using RNA Ligase-Mediated Rapid Amplification of cDNA Ends (RLM-RACE) to identify novel transcripts in conjunction with a highly sensitive, exon-specific multiplexed mRNA expression assay, we detected differential regulation of distinct ANK3 transcription start sites (TSSs) and coupling of specific 5’ ends with 3’ mRNA splicing events in post-mortem human brain and human stem cell-derived neural progenitors and neurons. Furthermore, allelic variation at the BD–associated SNP rs1938526 correlated with a significant difference in cerebellar expression of a brain-specific ANK3 transcript. These findings suggest a brain-specific cis-regulatory transcriptional effect of ANK3 may be relevant to BD pathophysiology

Current management of treatment-induced bone loss in women with breast cancer treated in the United Kingdom

New therapeutic options in breast cancer have improved survival but consequently increase the relevance of late complications. Ovarian suppression/ablation and aromatase inhibitors (AI) in the adjuvant setting have improved outcome, but have clinically important adverse effects on bone health. However, investigation and management of cancer treatment-induced bone loss (CTIBL) is poorly defined with no national guidance. In 2004, a questionnaire was sent to over 500 breast surgeons and oncologists who treat breast cancer within the United Kingdom. The questionnaire evaluated access to bone densitometry and specialist expertise as well as attitudes to investigation of CTIBL and anticipated changes in the use of AI for postmenopausal early breast cancer. A total of 354 completed questionnaires were received, 47 from clinicians not currently treating breast cancer. Of the 307 evaluable questionnaires, 164 (53%) were from breast surgeons, 112 (36%) from clinical oncologists and 31 (10%) from medical oncologists. Although most respondents recognised that CTIBL was the responsibility of the treating breast team, investigations for CTIBL are limited even though most had adequate access to bone densitometry; 98 (32%) had not requested a DXA scan in the last 6 months and 224 (73%) had requested fewer than five scans. In all, 235 (76%) were not routinely investigating patients on AI for bone loss. A total of 277 (90%) felt that their practice would benefit from national guidelines to manage these patients, and the majority (59%) had little or no confidence in interpreting DXA results and advising on treatment. This questionnaire has highlighted clear deficiencies in management of CTIBL in early breast cancer. The development of national guidelines for the management of these patients and educational initiatives for breast teams are urgently required

Assessment of Barotrauma Resulting from Rapid Decompression of Depth Acclimated Juvenile Chinook Salmon Bearing Radio Telemetry Transmitters

A multifactor study was conducted by Battelle for the US Army Corps of Engineers to assess the significance of the presence of a radio telemetry transmitter on the effects of rapid decompression from simulated hydro turbine passage on depth acclimated juvenile run-of-the-river Chinook salmon. Study factors were: (1) juvenile chinook salmon age;, subyearling or yearling, (2) radio transmitter present or absent, (3) three transmitter implantation factors: gastric, surgical, and no transmitter, and (4) four acclimation depth factors: 1, 10, 20, and 40 foot submergence equivalent absolute pressure, for a total of 48 unique treatments. Exposed fish were examined for changes in behavior, presence or absence of barotrauma injuries, and immediate or delayed mortality. Logistic models were used to test hypotheses that addressed study objectives. The presence of a radio transmitter was found to significantly increase the risk of barotrauma injury and mortality at exposure to rapid decompression. Gastric implantation was found to present a higher risk than surgical implantation. Fish were exposed within 48 hours of transmitter implantation so surgical incisions were not completely healed. The difference in results obtained for gastric and surgical implantation methods may be the result of study design and the results may have been different if tested fish had completely healed surgical wounds. However, the test did simulate the typical surgical-release time frame for in-river telemetry studies of fish survival so the results are probably representative for fish passing through a turbine shortly following release into the river. The finding of a significant difference in response to rapid decompression between fish bearing radio transmitters and those not implies a bias may exist in estimates of turbine passage survival obtained using radio telemetry. However, the rapid decompression (simulated turbine passage) conditions used for the study represented near worst case exposure for fish passing through turbines. At this time, insufficient data exist about the distribution of river-run fish entering turbines, and particularly, the distribution of fish passing through turbine runners, to extrapolate study findings to the population of fish passing through FCRPS turbines. This study is the first study examining rapid decompression study to include acclimation depth as an experimental factor for physostomous fish. We found that fish acclimated to deeper depth were significantly more vulnerable to barotrauma injury and death. Insufficient information about the distribution of fish entering turbines and their depth acclimation currently exists to extrapolate these findings to the population of fish passing through turbines. However, the risk of barotrauma for turbine-passed fish could be particularly high for subyearling Chinook salmon that migrate downstream at deeper depths late in the early summer portion of the outmigration. Barotrauma injuries led to immediate mortality delayed mortality and potential mortality due to increased susceptibility to predation resulting from loss of equilibrium or swim bladder rupture

Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin

Background Uromodulin, the most abundant protein excreted in normal urine, plays major roles in kidney physiology and disease. The mechanisms regulating the urinary excretion of uromodulin remain essentially unknown. Methods We conducted a meta-analysis of genome-wide association studies for raw (uUMOD) and indexed to creatinine (uUCR) urinary levels of uromodulin in 29,315 individuals of European ancestry from 13 cohorts. We tested the distribution of candidate genes in kidney segments and investigated the effects of keratin-40 (KRT40) on uromodulin processing. Results Two genome-wide significant signals were identified for uUMOD: a novel locus (P 1.24E-08) over the KRT40 gene coding for KRT40, a type 1 keratin expressed in the kidney, and the UMOD-PDILT locus (P 2.17E-88), with two independent sets of single nucleotide polymorphisms spread over UMOD and PDILT. Two genome-wide significant signals for uUCR were identified at the UMOD-PDILT locus and at the novel WDR72 locus previously associated with kidney function. The effect sizes for rs8067385, the index single nucleotide polymorphism in the KRT40 locus, were similar for both uUMOD and uUCR. KRT40 colocalized with uromodulin and modulating its expression in thick ascending limb (TAL) cells affected uromodulin processing and excretion. Conclusions Common variants in KRT40,WDR72, UMOD, and PDILT associate with the levels of uromodulin in urine. The expression of KRT40 affects uromodulin processing in TAL cells. These results, although limited by lack of replication, provide insights into the biology of uromodulin, the role of keratins in the kidney, and the influence of the UMOD-PDILT locus on kidney function

Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis

The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A meta-analysis of 10 studies was performed to determine the impact of the PCSK9 R46L variant on CAVS, and the authors found that CAVS was less prevalent in carriers of this variant (odds ratio: 0.80 [95% confidence interval: 0.70 to 0.91]; p = 0.0011) compared with noncarriers. PCSK9 expression was higher in the aortic valves of patients CAVS compared with control patients. In human valve interstitials cells submitted to a pro-osteogenic medium, PCSK9 levels increased and a PCSK9 neutralizing antibody significantly reduced calcium accumulation

Bone resorption predicts for skeletal complications in metastatic bone disease

Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0–3 months) and 95 patients over the second 3-month period (4–6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r=0.62, P<0.001 for 0–3 months and r=0.46, P<0.001 for 4–6 months, respectively). Patients with baseline Ntx values greater than or equal to100 nmol mmol−1 creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx <100 (P<0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment

Are all prognostic factors in parotid gland carcinoma well recognized?

The aim of his study was to assess the treatment results and prognostic factors in patients with parotid gland carcinoma. The material consisted of 109 patients treated surgically, with or without complementary radiotherapy, between 1978 and 2008 (follow-up at least 5-years). 5-year overall and disease-specific survival were observed in 57.0% of the patients and 5-year disease-free survival was achieved in 50.0%. Univariate analysis including ten clinical and pathological features to assess their prognostic value was done. Parapharyngeal space invasion, facial nerve palsy, and high grade of tumor malignancy were the factors with the highest influence on the treatment results, because their presence decreased the chance for recovery 9.8, 9.7, and 8.2 times, respectively. Histologically positive cervical lymph nodes and extraparenchymal extension were the other factors connected with poor prognosis (prognosis worse 6.7 and 5.4 times, respectively). Clinically positive cervical lymph nodes, positive/uncertain microscopic margin, involvement of the deep lobe, or the whole gland increased the risk of treatment failure 3.4, 3.1, and 2.8, respectively. The age ≥60 years and male gender were statistically significant factors, correlated with poor prognosis and decreased chance for recovery 2.4 and 2.6 times. T-status and clinical stage had important influence on 5-year disease-free survival rate because there were significant differences in the treatment results between individual stages. Multivariate analysis proved that the independent prognostic value, among anatomic structures involved by the neoplasm, had mandible, facial nerve, and skin infiltration. Among tumor-related factors, T-stage and grade had the statistically significant influence on treatment results, and stage and lymph nodes metastases among clinical and pathological features. These results confirm the value of actually used TNM classification (2002). Although the parapharyngeal space invasion is a factor, which seems to have a significant, poor prognostic value, it was not included in this classification