Grounding the internet : categorising the geographies of locative media

Taxonometrical uncertainty is prevalent in the field of locative media, which has been variously referred to as “the geomobile web” (Crawford and Goggin, 2009), “the geoweb” (Lake et al., 2004), “Where 2.0” (O’Reilly, 2008:1), and “DigiPlace” (Zook and Graham, 2007). However, it is not only the rapid development of the technology, or the various academic disciplinary approaches to it, that have resulted in this uncertainty but also the deeply ideological debates and concerns about what locative media should and should not be. The intention of this article is to provide an overview of existing literature and research in this field in order to develop a synthetic overview of the various types of locative media, and the geographies arising from them. Not only will such taxonomy clarify communication about locative media, it will identify for developers, users, policy-makers and scholars the specific contours and affordances of the different types of locative media, as well as the issues associated with them.

Effects of oxygen on zonal marker expression in human articular chondrocytes

Articular cartilage is organized in depth zones with phenotypically distinct subpopulations of chondrocytes that are exposed to different oxygen tensions. Despite growing evidence of the critical role for oxygen in chondrogenesis, little is known about its effect on chondrocytes from different zones. This study evaluates zonal marker expression of human articular chondrocytes from different zones under various oxygen tensions. Chondrocytes isolated from full-thickness, superficial, and middle/deep cartilage from knee replacement surgeries were expanded and redifferentiated under hypoxic (5% O 2) or normoxic (20% O 2) conditions. Differentiation under hypoxia increased expression of hypoxia-inducible factors 1alpha and 2alpha and accumulation of extracellular matrix, particularly in middle/deep chondrocytes, and favored re-expression of proteoglycan 4 by superficial chondrocytes compared with middle/deep cells. Zone-dependent expression of clusterin varied with culture duration. These results demonstrate that zonal chondrocytes retain important phenotypic differences during in vitro cultivation, and that these characteristics can be improved by altering the oxygen environment. However, transcript levels for pleiotrophin, cartilage intermediate layer protein, and collagen type X were similar between zones, challenging their reliability as zonal markers for tissue-engineered cartilage from osteoarthritis patients. Key factors including oxygen tension and cell source should be considered to prescribe zone-specific properties to tissue-engineered cartilage. © 2012, Mary Ann Liebert, Inc.

The microRNA expression signature on modified titanium implant surfaces influences genetic mechanisms leading to osteogenic differentiation

Topographically and chemically modified titanium implants are recognized to have improved osteogenic properties; however, the molecular regulation of this process remains unknown. This study aimed to determine the microRNA profile and the potential regulation of osteogenic differentiation following early exposure of osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF-β/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca2+ (WNT5A, FZD6) pathways, as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that the modified titanium surfaces could induce the activation of TGF-β/BMP and non-canonical WNT/Ca2+ signaling genes. The expression pattern of microRNAs (miRNAs) related to cell differentiation was evaluated. Statistical analysis of the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down-regulated on the modSLA and SLA surfaces respectively, when compared with the smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA surfaces, amongst which eight were the same as observed on modSLA. TargetScan predictions for the down-regulated miRNAs revealed genes of the TGF-β/BMP and non-canonical Ca2+ pathways as targets. This study demonstrated that modified titanium implant surfaces induce differential regulation of miRNAs, which potentially regulate the TGF-β/BMP and WNT/Ca2+ pathways during osteogenic differentiation on modified titanium implant surfaces.

Is flapless implant surgery a viable option in posterior maxilla? : a review

This article reviews the literature on the outcome of flapless surgery for dental implants in the posterior maxilla. The literature search was carried out in using the keywords: flapless, dental implants and maxilla. A hand search and Medline search were carried out on studies published between 1971 and 2011. The authors included research involving a minimum of 15 dental implants with a followup period of 1 year, an outcome measurement of implant survival, but excluded studies involving multiple simultaneous interventions, and studies with missing data. The Cochrane approach for cohort studies and Oxford Centre for Evidence- Based Medicine were applied. Of the 56 published papers selected, 14 papers on the flapless technique showed high overall implant survival rates. The prospective studies yielded 97.01% (95% CI: 90.72–99.0) while retrospective studies or case series illustrated 95.08% (95% CI: 91.0–97.93) survival. The average of intraoperative complications was 6.55% using the flapless procedure. The limited data obtained showed that flapless surgery in posterior maxilla areas could be a viable and predictable treatment method for implant placement. Flapless surgery tends to be more applicable in this area of the mouth. Further long-term clinical controlled studies are needed.

Shortening cemented femoral implants. An in vitro investigation to quantify exeter femoral implant rotational stability vs simulated implant length

The Exeter stems vary in length from 90 to 150 mm. The shorter stems generally have lower offsets. The purpose of this study was to determine if length of stem, with fixed offset, affected rotational stability. Mechanical testing was carried out on 10 implant-cement constructs with 2 loading profiles, rising from chair and stair climbing, at different simulated implant lengths using purpose-built apparatus. This paper presents a mechanism for clinically observed rotational stability and explains the mechanical characteristics required for rotational stability in Exeter femoral stems. © 2012.

Non-destructive evaluation of articular cartilage defects using near-infrared (NIR) spectroscopy in osteoarthritic rat models and its direct relation to Mankin Score

Objective The aim of this study was to demonstrate the potential of near-infrared (NIR) spectroscopy for categorizing cartilage degeneration induced in animal models. Method Three models of osteoarthritic degeneration were induced in laboratory rats via one of the following methods: (i) menisectomy (MSX); (ii) anterior cruciate ligament transaction (ACLT); and (iii) intra-articular injection of mono-ido-acetete (1 mg) (MIA), in the right knee joint, with 12 rats per model group. After 8 weeks, the animals were sacrificed and tibial knee joints were collected. A custom-made nearinfrared (NIR) probe of diameter 5 mm was placed on the cartilage surface and spectral data were acquired from each specimen in the wavenumber range 4 000 – 12 500 cm−1. Following spectral data acquisition, the specimens were fixed and Safranin–O staining was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis based on principal component analysis and partial least squares regression, the spectral data were then related to the Mankinscores of the samples tested. Results Mild to severe degenerative cartilage changes were observed in the subject animals. The ACLT models showed mild cartilage degeneration, MSX models moderate, and MIA severe cartilage degenerative changes both morphologically and histologically. Our result demonstrate that NIR spectroscopic information is capable of separating the cartilage samples into different groups relative to the severity of degeneration, with NIR correlating significantly with their Mankinscore (R2 = 88.85%). Conclusion We conclude that NIR is a viable tool for evaluating articularcartilage health and physical properties such as change in thickness with degeneration.

Dynamics of rod and cone photoreceptor interactions under mesopic light levels

Visual adaptation regulates contrast sensitivity during dynamically changing light conditions (Crawford, 1947; Hecht, Haig & Chase, 1937). These adaptation dynamics are unknown under dim (mesopic) light levels when the rod (R) and long (L), medium (M) and short (S) wavelength cone photoreceptor classes contribute to vision via interactions in shared non-opponent Magnocellular (MC), chromatically opponent Parvocellular (PC) and Koniocellular (KC) visual pathways (Dacey, 2000). This study investigated the time-course of adaptation and post-receptoral pathways mediating receptor specific rod and cone interactions under mesopic illumination. A four-primary photostimulator (Pokorny, Smithson & Quinlan, 2004) was used to independently control the activity of the four photoreceptor classes and their post-receptoral visual athways in human observers. In the first experiment, the contrast sensitivity and time-course of visual adaptation under mesopic illumination were measured for receptoral (L, S, R) and post-receptoral (LMS, LMSR, L-M) stimuli. An incremental (Rapid-ON) sawtooth conditioning pulse biased detection to ON-cells within the visual pathways and sensitivity was assayed relative to pulse onset using a briefly presented incremental probe that did not alter adaptation. Cone.Cone interactions with luminance stimuli (L cone, LMS, LMSR) reduced sensitivity by 15% and the time course of recovery was 25± 5ms-1 (μ ± SEM). PC mediated (+L-M) chromatic stimuli sensitivity loss was less (8%) than for luminance and recovery was slower (μ = 2.95 ± 0.05 ms-1), with KC mediated (S cone) chromatic stimuli showing a high sensitivity loss (38%) and the slowest recovery time (1.6 ± 0.2 ms-1). Rod-Rod interactions increased sensitivity by 20% and the time course of recovery was 0.7 ± 0.2 ms-1 (μ ± SD). Compared to these interaction types, Rod-Cone interactions reduced sensitivity to a lesser degree (5%) and showed the fastest recovery (μ = 43 ± 7 ms-1). In the second experiment, rod contribution to the magnocellular, parvocellular and koniocellular post-receptoral pathways under mesopic illumination was determined as a function of incremental stimulus duration and waveform (rectangular; sawtooth) using a rod colour match procedure (Cao, Pokorny & Smith, 2005; Cao, Pokorny, Smith & Zele, 2008a). For a 30% rod increment, a cone match required a decrease in [L/(L+M)] and an increase in [L+M] and [S/(L+M)], giving a greenish-blue and brighter appearance for probe durations of 75 ms or longer. Probe durations less than 75 ms showed an increase in [L+M] and no change in chromaticity [L/(L+M) or S/(L+M)], uggesting mediation by the MC pathway only for short duration rod stimuli. s We advance previous studies by determining the time-course and nature of photoreceptor specific retinal interactions in the three post-receptoral pathways under mesopic illumination. In the first experiment, the time-course of adaptation for ON cell processing was determined, revealing opponent cell facilitation in chromatic PC and KC pathways. The Rod-Rod and Rod-Cone data identify previously unknown interaction types that act to maintain contrast sensitivity during dynamically changing light conditions and improve the speed of light adaptation under mesopic light levels. The second experiment determined the degree of rod contribution to the inferred post-eceptoral pathways as a function of the temporal properties of the rod signal. r The understanding of the mechanisms underlying interactions between photoreceptors under mesopic illumination has implications for the study of retinal disease. Visual function has been shown to be reduced in persons with age-related maculopathy (ARM) risk genotypes prior to clinical signs of the disease (Feigl, Cao, Morris & Zele, 2011) and disturbances in rod-mediated adaptation have been shown in early phases of ARM (Dimitrov, Guymer, Zele, Anderson & Vingrys, 2008; Feigl, Brown, Lovie-Kitchin & Swann, 2005). Also, the understanding of retinal networks controlling vision enables the development of international lighting standards to optimise visual performance nder dim light levels (e.g. work-place environments, transportation).

Vertical Inhibition of the PI3K/Akt/mTOR Pathway for the Treatment of Osteoarthritis

Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome.

Implantation of osteogenic differentiated donor mesenchymal stem cells causes recruitment of host cells

The interaction between host and donor cells is believed to play an important role in osteogenesis. However, it is still unclear how donor osteogenic cells behave and interact with host cells in vivo. The purpose of this study was to track the interactions between transplanted osteogenic cells and host cells during osteogenesis. In vitro migration assay was carried out to investigate the ability of osteogenic differentiated humanmesenchymal stemcells (O-hMSCs) to recruit MSCs. At the in vivo level, O-hMSCs were implanted subcutaneously or into skull defects in severe combined immunodeficient (SCID) mice. New bone formation was observed bymicro-CT and histological procedures. In situ hybridization (ISH) against human Alu sequences was performed to distinguish donor osteogenic cells from host cells. In vitro migration assay revealed an increased migration potential of MSCs by co-culturing with O-hMSCs. In agreement with the results of in vitro studies, ISH against human Alu sequences showed that host mouse MSCs migrated in large numbers into the transplantation site in response to O-hMSCs. Interestingly, host cells recruited by O-hMSCs were the major cell populations in newly formed bone tissues, indicating that O-hMSCs can trigger and initiate osteogenesis when transplanted in orthotopic sites. The observations fromthis study demonstrated that in vitro induced O-hMSCs were able to attract hostMSCs in vivo andwere involved inosteogenesis togetherwith host cells,whichmay be of importance for bone tissue-engineering applications.

Combination of MEK-ERK inhibitor and hyaluronic acid has a synergistic effect on anti-hypertrophic and pro-chondrogenic activities in osteoarthritis treatment

We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug such as hyaluronic acid (HA) given in combination with anti-inflammatory signalling agents such as mitogen-activated protein kinase kinase–extracellular signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in additive or synergistic effects on preventing the degeneration of articular cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human OA primary cells treated with either HA or U0126, or the combination of HA + U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was investigated by intra-articular delivery of either HA or U0126, or the combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting and zymography were performed to assess the expression of cartilage matrix proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive chondrocytes were significantly higher in OA samples compared with those in healthy control suggesting the pathological role of that pathway in OA. It was noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP-13), however, increased the levels of chondrogenic markers (COL2) compared to untreated or the application of HA or U0126 alone. In agreement with the results in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic improvement of cartilage in rat MSX OA model compared with untreated or the application of HA or U0126 alone. Our study suggests that the combination of HA and MEK-ERK inhibition has a synergistic effect on preventing cartilage degeneration.

Exeter short stems compared with standard length Exeter stems : experience from the Australian Orthopaedic Association National Joint Replacement Registry

The standard Exeter stem has a length of 150mm with offsets 37.5mm to 56mm. Shorter stems of lengths 95mm, 115mm and 125mm with offsets 35.5mm or less are available for patients with smaller femurs. Concern has been raised regarding the behaviour of the smaller implants. This paper analysed data from the Australian Orthopaedic Association National Joint Replacement Registry comparing survivorship of stems of offset 35.5mm or less with the standard stems of 37.5mm offset or greater. At seven years there was no significant difference in the Cumulative Percent Revision Rate in the short stems (3.4%, 95% CI 2.4-4.8%) compared with the standard length stems (3.5%, 95% CI 3.3-3.8%) despite its use in a greater proportion of potentially more difficult developmental dysplasia of the hip cases.

Effects of oxygen and culture system on in vitro propagation and redifferentiation of osteoarthritic human articular chondrocytes

Regenerative medicine-based approaches for the repair of damaged cartilage rely on the ability to propagate cells while promoting their chondrogenic potential. Thus, conditions for cell expansion should be optimized through careful environmental control. Appropriate oxygen tension and cell expansion substrates and controllable bioreactor systems are probably critical for expansion and subsequent tissue formation during chondrogenic differentiation. We therefore evaluated the effects of oxygen and microcarrier culture on the expansion and subsequent differentiation of human osteoarthritic chondrocytes. Freshly isolated chondrocytes were expanded on tissue culture plastic or CultiSpher-G microcarriers under hypoxic or normoxic conditions (5% or 20% oxygen partial pressure, respectively) followed by cell phenotype analysis with flow cytometry. Cells were redifferentiated in micromass pellet cultures over 4 weeks, under either hypoxia or normoxia. Chondrocytes cultured on tissue culture plastic proliferated faster, expressed higher levels of cell surface markers CD44 and CD105 and demonstrated stronger staining for proteoglycans and collagen type II in pellet cultures compared with microcarrier-cultivated cells. Pellet wet weight, glycosaminoglycan content and expression of chondrogenic genes were significantly increased in cells differentiated under hypoxia. Hypoxia-inducible factor-3alpha mRNA was up-regulated in these cultures in response to low oxygen tension. These data confirm the beneficial influence of reduced oxygen on ex vivo chondrogenesis. However, hypoxia during cell expansion and microcarrier bioreactor culture does not enhance intrinsic chondrogenic potential. Further improvements in cell culture conditions are therefore required before chondrocytes from osteoarthritic and aged patients can become a useful cell source for cartilage regeneration.

Complications related to therapeutic anticoagulation in total hip arthroplasty

Bleeding related wound complications cause significant morbidity in lower limb arthroplasty surgery. Patients who require therapeutic anticoagulation in the peri operative period are potentially at higher risk of these complications. This is a retrospective case control study reviewing all primary total hip replacements performed in a single center over a five year period and comparing outcomes of the patients on warfarin with a double-matched control group of patients not on warfarin. The warfarin group had significantly higher risk of deep joint infection (9% vs 2.2%), haematoma/ wound ooze (28% vs 4%) and superficial infection (13.5% vs 2.2%). Managing the total hip arthroplasty patient with therapeutic anticoagulation is a balance between the risk of thromboembolic disease and bleeding related complications. Improved understanding of this risk will better allow the patient to make an informed decision regarding their elective arthroplasty surgery.