A multiscale model to predict current absolute risk of femoral fracture in a postmenopausal population

Osteoporotic hip fractures are a major healthcare problem. Fall severity and bone strength are important risk factors of hip fracture. This study aims to obtain a mechanistic explanation for fracture risk in dependence of these risk factors. A novel modelling approach is developed that combines models at different scales to overcome the challenge of a large space–time domain of interest and considers the variability of impact forces between potential falls in a subject. The multiscale model and its component models are verified with respect to numerical approximations made therein, the propagation of measurement uncertainties of model inputs is quantified, and model predictions are validated against experimental and clinical data. The main results are model predicted absolute risk of current fracture (ARF0) that ranged from 1.93 to 81.6% (median 36.1%) for subjects in a retrospective cohort of 98 postmenopausal British women (49 fracture cases and 49 controls); ARF0 was computed up to a precision of 1.92 percentage points (pp) due to numerical approximations made in the model; ARF0 possessed an uncertainty of 4.00 pp due to uncertainties in measuring model inputs; ARF0 classified observed fracture status in the above cohort with AUC = 0.852 (95% CI 0.753–0.918), 77.6% specificity (95% CI 63.4–86.5%) and 81.6% sensitivity (95% CI 68.3–91.1%). These results demonstrate that ARF0 can be computed using the model with sufficient precision to distinguish between subjects and that the novel mechanism of fracture risk determination based on fall dynamics, hip impact and bone strength can be considered validated.

     

Phase precession in the human hippocampus and entorhinal cortex

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Fictibacillus enclensis sp. nov., isolated from marine sediment

A novel Gram-positive strain, designated NIO-1003^T, was isolated from a marine sediment sample collected from the Chorao Island, Goa Provence, India. Strain NIO-1003^T was found to be strictly aerobic, motile, endospore-forming rods. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NIO-1003^T belongs to the genus Fictibacillus and to be most closely related to Fictibacillus rigui KCTC 13278^T, Fictibacillus solisalsi KCTC 13181^T and Fictibacillus barbaricus DSM 14730^T with 98.2, 98.0 and 97.2 % similarity and 25, 28, 39 nucleotide differences respectively. Strain NIO-1003^T was characterized by having cell-wall peptidoglycan based on meso-diaminopimelic acid and MK-7 as the predominant menaquinone. The polar lipid profile exhibited the major compounds diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. In addition, minor amounts of an aminophospholipid were detected. The major fatty acids were identified as ai-C_15:0, iso-C_15:0, ai-C_17:0 and C_16:0, supporting the grouping of strain NIO-1003^T into the family Bacillaceae. The DNA G+C content of strain NIO-1003^T was determined to be 42.6 mol%. On the basis of phenotypic properties, phylogeny and DNA–DNA hybridisation analysis, strain NIO-1003^T is considered to represent a novel species of the genus Fictibacillus for which the name Fictibacillus enclensis sp. nov. is proposed. The type strain is NIO-1003^T (= NCIM 5458^T = DSM 25142^T).     

Genomic triumph meets clinical reality

A report on the ''Genomic Disorders 2013: from 60 years of DNA to human genomes in the clinic'' meeting, held at Homerton College, Cambridge, UK, April 10-12, 2013.A meeting about genetics held in April 2013 in Cambridge, UK, started laden with historical overtones: it was 60 years to the month since the structure of DNA was reported as a result of work carried out by Watson and Crick just a short walk away. This year''s Genomic Disorders 2013 meeting was thus subtitled ''From 60 years of DNA to human genomes in the clinic'' and reflected on both the spectacular progress that has been achieved in these six decades, and also on the barriers to further advances.It has indeed been a remarkable journey. Progress in sequencing technologies has led to near-complete genome sequences of thousands of humans at a fraction of the cost of the Human Genome Project and prompted the push into clinical medicine, always a goal of the project. Within a working lifetime, the field had made a dramatic transition, likened to that from medieval guild to modern factory (Richard Durbin, The Wellcome Trust Sanger Institute, UK) or from the first car (which had to be preceded by a man walking with a red flag) towards the modern automobile industry (Robert C Green, Brigham and Women''s Hospital and Harvard Medical School, USA).In addition to celebrating the past, the major stumbling blocks on the road to clinical medicine came up during several rounds of discussions and are a main focus of this report. The challenges can be grouped as technological, annotation-related, biological or ethical, and seem to increase in difficulty and complexity in that order.     

Phenotypic and Molecular Characterization of Wheat for Slow Rusting Resistance against Puccinia striiformis Westend. f.sp. tritici

Race‐specific resistance of wheat (Triticum aestivum L.) to yellow rust caused by Puccinia striiformis Westend. f.sp. tritici is often short‐lived. Slow‐rusting resistance has been reported to be a more durable type of resistance. A set of sixteen bread wheat varieties along with a susceptible control Morocco was tested during 2004–05 to 2006–07 in field plots at Peshawar (Pakistan) to identify slow rusting genotypes through epidemiological variables including final rust severity (FRS), apparent infection rate (r), area under disease progress curve (AUDPC), average coefficients of infection (ACI) and leaf tip necrosis (LTN). Epidemiological parameters of resistance were significantly (P < 0.01) different for years/varieties in three seasons, while variety × year interactions remained non‐significant. Sequence tagged site (STS) marker, csLV34 analyses revealed that cultivars Faisalabad‐83, Bahawalpur‐95, Suleman‐96, Punjab‐96, Bakhtawar‐93, Faisalabad‐85, Shahkar‐95 and Kohsar‐95 possessed Yr18 linked allele. Faisalabad‐83, Bahawalpur‐95, Suleman‐96, Punjab‐96, Bakhtawar‐93 and Faisalabad‐85 were relatively more stable over 3‐years where FRS, AUDPC and r values reduced by 80, 84 and 70% respectively compared to control Morocco. These six varieties therefore could be exploited for the deployment of Yr18 in breeding for slow rusting in wheat. Both FRS and ACI are suitable parameters for phenotypic selection.     

Effects of rGM-CSF on leukemia cell proliferation and on the incorporation of cytosine arabinoside into DNA.

In vitro studies of the effects of recombinant granulocyte macrophage-colony stimulating factor (rGM-CSF) on freshly obtained human leukemia cells were conducted to determine if there is a relationship between the effects of this growth factor on the proliferative characteristics of leukemia cells and on their incorporation of cytosine arabinoside (araC) into DNA. While rGM-CSF was found to be able to stimulate both leukemia cell proliferation and araC incorporation, for individual leukemia specimens there was no consistent relationship among these effects. In some specimens proliferation was stimulated without an increase in araC incorporation. The reverse was also observed. These studies demonstrate the difficulty in identifying assays capable of predicting the clinical effects of growth factors on leukemia cells in patients since the effect in vitro vary with the assay.