Numerical resolution effects on simulations of massive black hole seeds

We have performed high-resolution numerical simulations with the hydrodynamical AMR code Enzo to investigate the formation of massive seed black holes in a sample of six dark matter haloes above the atomic cooling threshold. The aim of this study is to illustrate the effects of varying the maximum refinement level on the final object formed. The virial temperatures of the simulated haloes range from $\rm{T} \sim 10000\ \rm{K} - 16000\ \rm{K}$ and they have virial masses in the range $\rm{M} \sim 2 \times 10^7 \rm{M_{\odot}}$ to $\rm{M} \sim 7 \times 10^7 \rm{M_{\odot}}$ at $z \sim 15$. The outcome of our six fiducial simulations is both generic and robust. A rotationally supported, marginally gravitationally stable, disk forms with an exponential profile. The mass and scale length of this disk depends strongly on the maximum refinement level used. Varying the maximum refinement level by factors between 1 / 64 to 256 times the fiducial level illustrates the care that must be taken in interpreting the results. The lower resolution simulations show tentative evidence that the gas may become rotationally supported out to 20 pc while the highest resolution simulations show only weak evidence of rotational support due to the shorter dynamical times for which the simulation runs. The higher resolution simulations do, however, point to fragmentation at small scales of the order of $\sim 100$ AU. In the highest resolution simulations a central object of a few times $10^2\ \rm{M_{\odot}}$ forms with multiple strongly bound, Jeans unstable, clumps of $\sim 10\ \rm{M_{\odot}}$ and radii of 10 - 20 AU suggesting the formation of dense star clusters in these haloes

Eta Carinae -- Physics of the Inner Ejecta

Eta Carinae's inner ejecta are dominated observationally by the bright Weigelt blobs and their famously rich spectra of nebular emission and absorption lines. They are dense (n_e ~ 10^7 to 10^8 cm^-3), warm (T_e ~ 6000 to 7000 K) and slow moving (~40 km/s) condensations of mostly neutral (H^0) gas. Located within 1000 AU of the central star, they contain heavily CNO-processed material that was ejected from the star about a century ago. Outside the blobs, the inner ejecta include absorption-line clouds with similar conditions, plus emission-line gas that has generally lower densities and a wider range of speeds (reaching a few hundred km/s) compared to the blobs. The blobs appear to contain a negligible amount of dust and have a nearly dust-free view of the central source, but our view across the inner ejecta is severely affected by uncertain amounts of dust having a patchy distribution in the foreground. Emission lines from the inner ejecta are powered by photoionization and fluorescent processes. The variable nature of this emission, occurring in a 5.54 yr event cycle, requires specific changes to the incident flux that hold important clues to the nature of the central object.Comment: This is Chapter 5 in a book entitled: Eta Carinae and the Supernova Impostors, Kris Davidson and Roberta M. Humphreys, editors Springe

Minor structural modifications to alchemix influence mechanism of action and pharmacological activity

Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumors. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in G1 supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies

Epidemiology of fractures in Armenia: development of a country-specific FRAX model and comparison to its surrogate

Summary: Fracture probabilities derived from the surrogate FRAX model for Armenia were compared to those from the model based on regional estimates of the incidence of hip fracture. Disparities between the surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. Objective: Armenia has relied on a surrogate FRAX model based on the fracture epidemiology of Romania. This paper describes the epidemiology of fragility fractures in Armenia used to create an Armenia-specific FRAX model with an aim of comparing this new model with the surrogate model. Methods: We carried out a population-based study in two regions of Armenia (Ararat and Vayots Dzor representing approximately 11% of the country’s population). We aimed to identify all low-energy fractures: retrospectively from hospital registers in 2011–2012 and prospectively in 2013 with the inclusion of primary care sources. Results: The differences in incidence between the surveys with and without data from primary care suggested that 44% of patients sustaining a hip fracture did not receive specialized medical care. A similar proportion of forearm and humeral fractures did not come to hospital attention (48 and 49%, respectively). Only 57.7% of patients sustaining a hip fracture were hospitalized. In 2013, hip fracture incidence at the age of 50 years or more was 201/100,000 for women and 136/100,000 for men, and age- and sex-specific rates were incorporated into the new “authentic” FRAX model for Armenia. Compared to the surrogate model, the authentic model gave lower 10-year fracture probabilities in men and women aged less than 70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the surrogate and authentic models ( >  0.99) so that the revisions had little impact on the rank order of risk. Conclusion: A substantial proportion of major osteoporotic fractures in Armenia do not come to hospital attention. The disparities between surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal

Epidemiology of hip fracture in Belarus: development of a country-specific FRAX model and its comparison to neighboring country models

Summary Fracture probabilities resulting from the newly generated FRAX model for Belarus based on regional estimates of the hip fracture incidence were compared with FRAX models of neighboring countries. Differences between the country-specific FRAX patterns and the rank orders of fracture probabilities were modest. Objective This paper describes the epidemiology of hip fractures in Belarus that was used to develop the country-specific fracture prediction FRAX® tool and illustrates its features compared to models for the neighboring countries of Poland, Russia, and Lithuania. Methods We carried out a population-based study in a region of Belarus (the city of Mozyr) representing approximately 1.2% of the country’s population. We aimed to identify all hip fractures in 2011–2012 from hospital registers and primary care sources. Age- and sex-specific incidence and national mortality rates were incorporated into a FRAX model for Belarus. Fracture probabilities were compared with those derived from FRAX models in neighboring countries. Results The estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 8250 in 2015 and is predicted to increase to 12,918 in 2050. The annual incidence of fragility hip fractures in individuals aged 50 years or more was 24.6/10,000 for women and 14.6/10,000 for men, standardized to the world population. The comparison with FRAX models in neighboring countries showed that hip fracture probabilities in men and women in Belarus were similar to those in Poland, Russia, and Lithuania. The difference in incidence rates between the surveys including or excluding data from primary care suggested that 29.1% of patients sustaining a hip fracture were not hospitalized and, therefore, did not receive specialized medical care. Conclusion A substantial proportion of hip fractures in Belarus does not come to hospital attention. The FRAX model should enhance accuracy of determining fracture probability among the Belarus population and help guide decisions about treatment

FRAX- vs. T-score-based intervention thresholds for osteoporosis

Many current guidelines for the assessment of osteoporosis, including those in Kuwait, initiate fracture risk assessment in men and women using BMD T-score thresholds. We compared the Kuwaiti guidelines with FRAX-based age-dependent intervention thresholds equivalent to that in women with a prior fragility fracture. FRAX-based intervention thresholds identified women at higher fracture probability than fixed T-score thresholds, particularly in the elderly. PURPOSE: A FRAX® model been recently calibrated for Kuwait, but guidance is needed on how to utilise fracture probabilities in the assessment and treatment of patients. METHODS: We compared age-specific fracture probabilities, equivalent to women with no clinical risk factors and a prior fragility fracture (without BMD), with the age-specific fracture probabilities associated with femoral neck T-scores of -2.5 and -1.5 SD, in line with current guidelines in Kuwait. Upper and lower assessment thresholds for BMD testing were additionally explored using FRAX. RESULTS: When a BMD T-score of -2.5 SD was used as an intervention threshold, FRAX probabilities of a major osteoporotic fracture in women aged 50 years were approximately twofold higher than those in women of the same age but with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 83 years or more, a T-score of -2.5 SD was associated with a lower probability of fracture than that of the age-matched general population with no clinical risk factors. The same phenomenon was observed from the age of 66 years at a T-score of -1.5 SD. A FRAX-based intervention threshold, defined as the 10-year probability of a major osteoporotic fracture in a woman of average BMI with a previous fracture, rose with age from 4.3% at the age of 50 years to 23%, at the age of 90 years, and identified women at increased risk at all ages. Qualitatively comparable findings were observed in the case of hip fracture probability and in men. CONCLUSION: Intervention thresholds based on BMD alone do not optimally target women at higher fracture risk than those on age-matched individuals without clinical risk factors, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' consistently target women at higher fracture risk, irrespective of age

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Clinical Observation Study of Massive Blood Transfusion in a Tertiary Care Hospital in Korea

PURPOSE: Massive blood transfusios are uncommon. The goal of this study was to propose an ideal ratio for the blood component of massive hemorrhage treatment after review of five years of massive transfusion practice, in order to have the best possible clinical outcomes. MATERIALS AND METHODS: We defined a 'massive transfusion' as receiving 10 or more units of red blood cells in one day. A list of patients receiving a massive transfusion from 2004 to 2008 was generated using the electronic medical records. For each case, we calculated the ratio of blood components and examined its relationship to their survival. RESULTS: Three hundred thirty four patients underwent massive transfusion during the five years of the study. The overall seven-day hospital mortality for massive transfusion patients was 26.1%. Factors independently predictive of survival were a fresh-frozen plasma (FFP)/packed red blood cell (pRBC) ratio ≥ 1.1 with an odds ratio (OR) of 1.96 (1.03-3.70), and elective admission with an OR of 2.6 (1.52-4.40). The receiver operation characteristic (ROC) curve suggest that a 1 : 1 : 1 ratio of pRBCs to FFP to platelets is the best ratio for survival. CONCLUSION: Fixing blood-component ratios during active hemorrhage shows improved outcomes. Thus, the hospital blood bank and physician hypothesized that a fixed blood component ratio would help to reduce mortality and decrease utilization of the overall blood componentope

Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX™)

SUMMARY: The present study estimated the 10-year probability using the Japanese version of WHO fracture risk assessment tool (FRAX) in order to determine fracture probabilities that correspond to intervention thresholds currently used in Japan and to resolve some issues for its use in Japan. INTRODUCTION: The objective of the present study was to evaluate a Japanese version of the WHO fracture risk assessment (FRAX) tool to compute 10-year probabilities of osteoporotic fracture in Japanese men and women. Since lumbar spine bone mineral density (BMD) is used preferentially as a site for assessment, and densitometers use Japanese reference data, a second aim was to investigate the suitability and impact of this practice in Japan. METHODS: Fracture probabilities were computed from published data on the fracture and death hazards in Japan. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. Fracture probabilities were determined that were equivalent to intervention thresholds currently used in Japan. The difference between T-scores derived from international reference data and that using Japanese-specific normal ranges was estimated from published sources. The gradient of risk of BMD for fracture in Japan was compared to that for BMD at the lumbar spine in the Hiroshima cohort. RESULTS: The 10-year probabilities of a major osteoporosis-related fracture that corresponded to current intervention thresholds ranged from approximately 5% at the age of 50 years to more than 20% at the age of 80 years. The use of femoral neck BMD predicts fracture as well as or better than BMD tests at the lumbar spine. There were small differences in T-scores between those used for the model and those derived from a Japanese reference population. CONCLUSIONS: The FRAX mark tool has been used to determine possible thresholds for therapeutic intervention, based on equivalence of risk with current guidelines. The approach will need to be supported by appropriate health economic analyses. Femoral neck BMD is suitable for the prediction of fracture risk among Japanese. However, when applying the FRAX model to Japan, T-scores and Z-scores should be converted to those derived from the international reference