Focal osteoporosis defects play a key role in hip fracture

$\textbf{BACKGROUND}$: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. $\textbf{METHODS}$: The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. $\textbf{RESULTS}$: Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. $\textbf{CONCLUSION}$: Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.Arthritis Research UK (grant no. ARC17822) and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre

IgM Promotes the Clearance of Small Particles and Apoptotic Microparticles by Macrophages

Background: Antibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a sizedependent effect on clearance. Methodology/Principal Findings: We used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal) and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1–2 micron) by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2–5 micron) and apoptotic microparticles (,2 mm) released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads. Conclusions/Significance: Therefore, while the shape of the particles is important for non-opsonized particle uptake, th

ASHRAE Seminar in Ottawa

NRC publication: N

Control of the IAQ conditions in office buildings by general ventilation - a simple guide

Peer reviewed: YesNRC publication: Ye

Simple guide to ventilating buildings for contaminant control

Peer reviewed: NoNRC publication: Ye

Maintaining indoor air quality through the use of HVAC systems

Aussi disponible en fran\ue7ais: Maintien de la qualit\ue9 de l'air int\ue9rieur au moyen des syst\ue8mes CVCAPeer reviewed: NoNRC publication: Ye

Air change rates and carbon dioxide concentrations in a high-rise office building

The feasibility of controlling ventilation rates using occupant-generated carbon dioxide (C02) as the control index has been examined in a large high-rise office building with a constant-volume heating, ventilating, and air-conditioning (HVAC) system. Daily C02 concentration profiles throughout the building and air change rates, using sulfurhexafluoride (SF6) as a tracer gas, were measured for several outdoor air supply rates. Of particular interest was how well the C02 concentrations measured in the centralventilation system's return air plenum represented the average C02 concentration behavior in the building as a whole. C02 concentration profiles were also measured onindividual floorspaces in the building to determine the range of variability in the concentration behavior in occupied zones. The influence of fresh air supply rates on the speed of mixing of the tracer gas (surrogate contaminant) was also examined. The practicability of using C02 as an active tracer gas to measure air change rates was also investigated. The results are discussed in the paper.La faisabilit\ue9 du contr\uf4le des taux de renouvellement d?air d?une pi\ue8ce en utilisant comme indice le bioxyde de carbone (C02) produit par ses occupants a \ue9t\ue9 \ue9tudi\ue9e dans un immeuble \ue0 bureaux de grande taille dot\ue9 d?un syst\ue8me de chauffage, de ventilation et de conditionnement d?air (CVCA) du type \ue0 volume constant. Les profils de concentration de C02 quotidiens \ue0 l?\ue9chelle du b\ue2timent en entier, ainsi que les d\ue9bits de renouvellement d?air, contr\uf4l\ue9s par utilisation de l?hexafluorure de soufre (SF6) comme gaz de d\ue9pistage, ont \ue9t\ue9 mesur\ue9s pour plusieurs taux diff\ue9rents d?approvisionnement en air ext\ue9rieur. Les concentrations de C02 mesur\ue9es dans le pl\ue9num de reprise d?air de l?installation de ventilation centrale refl\ue9taient avec beaucoup d?exactitude le comportement en termes de concentrations moyennes de C02 du b\ue2timent dans son ensemble, ce qui nous est apparu comme \ue9tant d?un int\ue9r\ueat particulier. On a mesur\ue9 les profils de concentration de C02 \ue9galement sur des surfaces utiles individuelles dans le b\ue2timent afin de d\ue9terminer la gamme de variabilit\ue9 du comportement en termes de concentration dans les zones occup\ue9es. L?incidence des taux d?approvisionnement en air frais sur la vitesse du m\ue9lange du gaz de d\ue9pistage (substitut d?agent contaminant) a aussi \ue9t\ue9 examin\ue9e, tout comme la possibilit\ue9 d?utiliser le C02 comme gaz de d\ue9pistage actif aux fins de la mesure des d\ue9bits de renouvellement d?air. Les r\ue9sultats de ces recherches sont ici expos\ue9s.Peer reviewed: YesNRC publication: Ye

Controlling Indoor Air Quality - Ventilation Engineering Guide

Peer reviewed: NoNRC publication: Ye

Computer simulation of ventilation strategies for maintaining an acceptable indoor air quality in office buildings

Peer reviewed: YesNRC publication: Ye