Application of homogenization theory to the study of trabecular bone mechanics

It is generally accepted that the strength and stiffness of trabecular bone is strongly affected by trabecular microstructure. It has also been hypothesized that stress induced adaptation of trabecular bone is affected by trabecular tissue level stress and/or strain. At this time, however, there is no generally accepted (or easily accomplished) technique for predicting the effect of microstructure on trabecular bone apparent stiffness and strength or estimating tissue level stress or strain. In this paper, a recently developed mechanics theory specifically designed to analyze microstructured materials, called the homogenization theory, is presented and applied to analyze trabecular bone mechanics. Using the homogenization theory it is possible to perform microstructural and continuum analyses separately and then combine them in a systematic manner. Stiffness predictions from two different microstructural models of trabecular bone show reasonable agreement with experimental results, depending on metaphyseal region, (R2>0.5 for proximal humerus specimens, R2 <0.5 for distal femur and proximal tibia specimens). Estimates of both microstructural strain energy density (SED) and apparent SED show that there are large differences (up to 30 times) between apparent SED (as calculated by standard continuum finite element analyses) and the maximum microstructural or tissue SED. Furthermore, a strut and spherical void microstructure gave very different estimates of maximum tissue SED for the same bone volume fraction (BV/TV). The estimates from the spherical void microstructure are between 2 and 20 times greater than the strut microstructure at 10-20% BV/TV.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29647/1/0000736.pd

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Metric analysis of ungulate mammals from the early Middle Pleistocene of Britain, in relation to taxonomy and biostratigraphy. I: Rhinocerotidae and Bovidae

Rhinoceroses (Stephanorhinus) and large bovids (Bison, Bos) from the early Middle Pleistocene of Britain are analysed with regard to their taxonomy, biometric variation, and possible biochronological significance. The localities considered are West Runton (type Cromerian), Pakefield, Westbury-sub-Mendip, and Boxgrove. The samples include important, previously undescribed material. Among the rhinos, in addition to the common Stephanorhinus hundsheimensis, upper dentitions from Pakefield and West Runton provide hints of undescribed taxa with affinity to, but distinct from, S. etruscus and S. hundsheimensis. At Boxgrove, a further rhino cf. S. megarhinus occurs, corroborating the chronological extension of this ‘Pliocene’ species into the Middle Pleistocene. A small bison referable to B. schoetensacki occurs at all sites, but in the Westbury Yellow Breccia (upper interglacial level) it is accompanied by a larger bison which may be B. priscus. Dental material from Pakefield provides evidence of additional, smaller bovid species, with features recalling Leptobos and Bubalus, but their identity is unclear; there is also larger material probably representing Bos, which if confirmed would be the oldest record of aurochs in the British Isles

Lower Paleolithic bone tools from the "Spear Horizon" at Schöningen (Germany)

Zooarchaeolog

Metric analysis of ungulate mammals from the early Middle Pleistocene of Britain, in relation to taxonomy and biostratigraphy. II: Cervidae, Equidae and Suidae

The taxonomy and biostratigraphic significance of horses (Equus), deer (Capreolus, Dama, Cervus, Cervalces, Praemegaceros, Megaloceros) and pigs (Sus) from key British early Middle Pleistocene sites are investigated using a biometric approach. The sites compared are West Runton (type Cromerian), Pakefield, Little Oakley, Westbury-sub-Mendip, and Boxgrove. The samples include a significant amount of previously undescribed material. Stenonid horses dominate at Pakefield and West Runton, caballines at Westbury and Boxgrove, corresponding to the Mimomys/Arvicola division. The deer of Boxgrove include relatively large roe and small red deer, the latter distinguishing it from the Westbury Pink Breccia. The poorly-known giant deer Praemegaceros dawkinsi spans both the Mimomys (Little Oakley, Pakefield) and Arvicola (Boxgrove) zones of the Cromerian Complex. There is a marked shift in cervid abundance from predominant megacerines (Mimomys zone) to predominant red deer (Arvicola zone)

Pronounced warmth during early Middle Pleistocene interglacials : investigating the Mid-Bruhnes Event in the British terrestrial sequence

The Mid-Brunhes Event (MBE) is a climatic transition occurring between MIS 13 and 11 that separates two climatic modes: (1) early Middle Pleistocene interglacials (780–450 ka) that are characterised by only moderate warmth and (2) Middle and Late Pleistocene interglacials (occurring after 450 ka) that are characterised by greater warmth consistent with, or warmer than, the Holocene. This event is observable within a variety of long climate records, such as SPECMAP and EPICA, but its effect on terrestrial systems is poorly understood. The impact of this event is examined in the British terrestrial sequence by comparing the occurrence of a range of thermophilous plant and animal species, and climate reconstructions derived from assemblages containing them, from interglacials of the early Middle Pleistocene with those from the late Middle and Late Pleistocene. This comparison reveals that interglacial climates during the early Middle Pleistocene in Britain were as warm as, and in some cases warmer than, those that occurred during the late Middle and Late Pleistocene. This interpretation is supported by sea surface temperature records in the North Atlantic, which show that temperatures during early Middle Pleistocene interglacials were at least as warm as those experienced during the Holocene. There is, therefore, no evidence in climate records of Britain and the North Atlantic for a Mid-Brunhes Event. This suggests that the MBE is not a global climatic transition but is restricted to specific regions, in particular the higher latitudes of the southern Hemisphere. Further work is needed to understand the regional variability and cause of the MBE