Enhanced glacial discharge from the eastern Antarctic Peninsula since the 1700s associated with a positive Southern Annular Mode.

The Antarctic Peninsula Ice Sheet is currently experiencing sustained and accelerating loss of ice. Determining when these changes were initiated and identifying the main drivers is hampered by the short instrumental record (1992 to present). Here we present a 6,250 year record of glacial discharge based on the oxygen isotope composition of diatoms (δ18Odiatom) from a marine core located at the north-eastern tip of the Antarctic Peninsula. We find that glacial discharge - sourced primarily from ice shelf and iceberg melting along the eastern Antarctic Peninsula - remained largely stable between ~6,250 to 1,620 cal. yr BP, with a slight increase in variability until ~720 cal. yr. BP. An increasing trend in glacial discharge occurs after 550 cal. yr BP (A.D. 1400), reaching levels unprecedented during the past 6,250 years after 244 cal. yr BP (A.D. 1706). A marked acceleration in the rate of glacial discharge is also observed in the early part of twentieth century (after A.D. 1912). Enhanced glacial discharge, particularly after the 1700s is linked to a positive Southern Annular Mode (SAM). We argue that a positive SAM drove stronger westerly winds, atmospheric warming and surface ablation on the eastern Antarctic Peninsula whilst simultaneously entraining more warm water into the Weddell Gyre, potentially increasing melting on the undersides of ice shelves. A possible implication of our data is that ice shelves in this region have been thinning for at least ~300 years, potentially predisposing them to collapse under intensified anthropogenic warming.

Osteomimetic matrix components alter cell migration and drug response in a 3D tumour-engineered osteosarcoma model.

Osteosarcoma management continues to lack the appropriate prognostic tools to assign personalised treatment. This leaves non-responders to standard care vulnerable to recurring disease and pulmonary metastases. Developing 3D in vitro disease models to serve as a test bed for personalised treatment is a promising approach to address this issue. This study describes the generation of 3D osteosarcoma models termed "tumouroids", which are geometrically compartmentalised to reproduce the bone cancer mass and its surrounding. Although the tumour microenvironment impacts osteosarcoma in many ways, this model focussed on interrogating the influence of a biomimetic matrix on tumour cell behaviour. The 3D matrix was supplemented with the bone-marrow proteins laminin, fibronectin and NuOss® bone granules. This led to increased invasion of osteosarcoma cell aggregates from within the bone-like matrix into the surrounding acellular bone marrow-like ECM. The presence of bone granules also yielded an atypical molecular profile of osteosarcoma cells, suggesting malignant metabolic reprogramming. Changes include decreased MMP-9 (p < 0.05) and increased PTEN (p < 0.05), MCP-1 (p < 0.01) and MCT-4 (p < 0.05) gene expression. This complex 3D biomimetic composition also changed cellular responses to doxorubicin, a common chemotherapeutic agent used to treat osteosarcoma, and reproduced key issues of in vivo treatment like drug penetrance and doxorubicin-induced bone toxicity. This work highlights the importance of a biomimetic matrix in 3D osteosarcoma models for both basic and translational research. STATEMENT OF SIGNIFICANCE: This study describes the generation of 3D osteosarcoma models termed "tumouroids", which are geometrically compartmentalised to reproduce the bone cancer mass and its environment. Utilising this novel model, specific parameters of osteosarcoma growth and invasion were investigated. Osteosarcoma cell lines proliferate at a slower rate, exhibit malignant metabolic reprogramming, and respond to drug intervention at lower concentrations of doxorubicin hydrochloride in matrix-complex compared to basic tumouroids. As such, this study provides evidence that the tumour microenvironment impacts osteosarcoma in many ways. The osteosarcoma tumouroid described herein may form the basis of a personalised-medicine strategy, which will allow the testing of drug effectiveness similar to that used for antibiotic selection for pathogenic bacteria.

Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.

BACKGROUND: Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. METHODS: hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-ß1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry. RESULTS: Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. CONCLUSION: Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Early warning of footpad dermatitis and hockburn in broiler chicken flocks using optical flow, bodyweight and water consumption.

Footpad dermatitis and hockburn are serious welfare and economic issues for the production of broiler (meat) chickens. The authors here describe the use of an inexpensive camera system that monitors the movements of broiler flocks throughout their lives and suggest that it is possible to predict, even in young birds, the cross-sectional prevalence at slaughter of footpad dermatitis and hockburn before external signs are visible. The skew and kurtosis calculated from the authors' camera-based optical flow system had considerably more power to predict these outcomes in the 50 flocks reported here than water consumption, bodyweight or mortality and therefore have the potential to inform improved flock management through giving farmers early warning of welfare issues. Further trials are underway to establish the generality of the results.

Current views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies.

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP-based biomaterials are produced and have been extensively used for dental and orthopaedic applications. This is justified by their biocompatibility, osteoconductivity and osteoinductivity (i.e. the intrinsic material property that initiates de novo bone formation), which are attributed to the chemical composition, surface topography, macro/microporosity and the dissolution kinetics. However, the exact molecular mechanism of action is unknown. This review paper first summarizes the most important aspects of bone biology in relation to CaP and the mechanisms of bone matrix mineralization. This is followed by the research findings on the effects of calcium (Ca²âº) and phosphate (PO4³â») ions on the migration, proliferation and differentiation of osteoblasts during in vivo bone formation and in vitro culture conditions. Further, the rationale of using CaP for bone regeneration is explained, focusing thereby specifically on the material's osteoinductive properties. Examples of different material forms and production techniques are given, with the emphasis on the state-of-the art in fine-tuning the physicochemical properties of CaP-based biomaterials for improved bone induction and the use of CaP as a delivery system for bone morphogenetic proteins. The use of computational models to simulate the CaP-driven osteogenesis is introduced as part of a bone tissue engineering strategy in order to facilitate the understanding of cell-material interactions and to gain further insight into the design and optimization of CaP-based bone reparative units. Finally, limitations and possible solutions related to current experimental and computational techniques are discussed.

Does tranexamic acid stabilised fibrin support the osteogenic differentiation of human periosteum derived cells?

Fibrin sealants have long been used as carrier for osteogenic cells in bone regeneration. However, it has not been demonstrated whether fibrin's role is limited to delivering cells to the bone defect or whether fibrin enhances osteogenesis. This study investigated fibrin's influence on the behaviour of human periosteum-derived cells (hPDCs) when cultured in vitro under osteogenic conditions in two-dimensional (fibrin substrate) and three-dimensional (fibrin carrier) environments. Tranexamic acid (TEA) was used to reduce fibrin degradation after investigating its effect on hPDCs in monolayer culture on plastic.TEA did not affect proliferation nor calcium deposition of hPDCs under these conditions. Expression profiles of specific osteogenic markers were also maintained within the presence of TEA, apart from reduced alkaline phosphatase (ALP) expression (day 14). Compared to plastic, proliferation was upregulated on 2D fibrin substrates with a 220% higher DNA content by day 21. Gene expression was also altered, with significantly (p<0.05) decreased Runx2 (day 7) and ALP (day 14) expression and increased collagen I expression (day 14 and 21). In contrast to plastic, mineralisation was absent on fibrin substrates. Inside fibrin carriers, hPDCs were uniformly distributed. Moderate cell growth and reduced osteogenic marker expression was observed inside fibrin carriers. After 2 weeks, increased cell death was present in the carrier's centre. In conclusion, fibrin negatively influences osteogenic differentiation, compared to culture plastic, but enhanced proliferation (at least in 2D cultures) for hPDCs cultured in osteogenic conditions. TEA maintained the integrity of fibrin-based constructs, with minor effects on the osteogenic differentiation of hPDCs.

A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling.

In this study, we investigated a clinically relevant model of in vivo ectopic bone formation utilizing human periosteum derived cells (HPDCs) seeded in a Collagraft carrier and explored the mechanisms by which this process is driven. Bone formation occurred after eight weeks when a minimum of one million HPDCs was loaded on Collagraft carriers and implanted subcutaneously in NMRI nu/nu mice. De novo bone matrix, mainly secreted by the HPDCs, was found juxta-proximal of the calcium phosphate (CaP) granules suggesting that CaP may have triggered the 'osteoinductive program'. Indeed, removal of the CaP granules by ethylenediaminetetraacetic acid decalcification prior to cell seeding and implantation resulted in loss of bone formation. In addition, inhibition of endogenous bone morphogenetic protein and Wnt signalling by overexpression of the secreted antagonists Noggin and Frzb, respectively, also abrogated osteoinduction. Proliferation of the engrafted HPDCs was strongly reduced in the decalcified scaffolds or when seeded with adenovirus-Noggin/Frzb transduced HPDCs indicating that cell division of the engrafted HPDCs is required for the direct bone formation cascade. These data suggest that this model of bone formation is similar to that observed during physiological intramembranous bone development and may be of importance when investigating tissue engineering strategies.

Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes.

Glucocorticoids (GC) are commonly used anti-inflammatory drugs, but long-term use can result in marked growth retardation in children due to their actions on growth plate chondrocytes. To gain an insight into the mechanisms involved in GC-induced growth retardation, we performed Affymetrix microarray analysis of the murine chondrogenic cell line ATDC5, incubated with 10(-6) M dexamethasone (Dex) for 24 h. Downregulated genes included secreted frizzled-related protein and IGF-I, and upregulated genes included serum/GC-regulated kinase, connective-tissue growth factor, and lipocalin 2. Lipocalin 2 expression increased 40-fold after 24-h Dex treatment. Expression increased further after 48-h (75-fold) and 96-h (84-fold) Dex treatment, and this response was Dex concentration dependent. Lipocalin 2 was immunolocalized to both proliferating and hypertrophic growth plate zones, and its expression was increased by Dex in primary chondrocytes at 6 h (3-fold, P < 0.05). The lipocalin 2 response was blocked by the GC-receptor antagonist RU-486 and was increased further by the protein synthesis blocker cycloheximide. Proliferation in lipocalin 2-overexpressing cells was less than in control cells (49%, P < 0.05), and overexpression caused an increase in collagen type X expression (4-fold, P < 0.05). The effects of lipocalin 2 overexpression on chondrocyte proliferation (64%, P < 0.05) and collagen type X expression (8-fold, P < 0.05) were further exacerbated with the addition of 10(-6) M Dex. This synergistic effect may be explained by a further increase in lipocalin 2 expression with Dex treatment of transfected cells (45%, P < 0.05). These results suggest that lipocalin 2 may mediate Dex effects on chondrocytes and provides a potential novel mechanism for GC-induced growth retardation.

Testing the assumptions of linear prediction analysis in normal vowels.

In this paper we develop an improved surrogate data test to show experimental evidence, for all the simple vowels of U.S. English, for both male and female speakers, that Gaussian linear prediction analysis, a ubiquitous technique in current speech technologies, cannot be used to extract all the dynamical structure of real speech time series. The test provides robust evidence undermining the validity of these linear techniques, supporting the assumptions of either dynamical nonlinearity and/or non-Gaussianity common to more recent, complex, efforts at dynamical modeling speech time series. However, an additional finding is that the classical assumptions cannot be ruled out entirely, and plausible evidence is given to explain the success of the linear Gaussian theory as a weak approximation to the true, nonlinear/non-Gaussian dynamics. This supports the use of appropriate hybrid linear/nonlinear/non-Gaussian modeling. With a calibrated calculation of statistic and particular choice of experimental protocol, some of the known systematic problems of the method of surrogate data testing are circumvented to obtain results to support the conclusions to a high level of significance.

Identification of Isolates that Cause a Leaf Spot Disease of Brassicas as Xanthomonas campestris pv. raphani and Pathogenic and Genetic Comparison with Related Pathovars.

ABSTRACT Twenty-five Xanthomonas isolates, including some isolates received as either X. campestris pv. armoraciae or pv. raphani, caused discrete leaf spot symptoms when spray-inoculated onto at least one Brassica oleracea cultivar. Twelve of these isolates and four other Xanthomonas isolates were spray- and pin-inoculated onto 21 different plant species/cultivars including horseradish (Armoracia rusticana), radish (Raphanus sativus), and tomato (Lycopersicon esculentum). The remaining 13 leaf spot isolates were spray-inoculated onto a subset of 10 plant species/cultivars. The leaf spot isolates were very aggressive on several Brassica spp., radish, and tomato causing leaf spots and dark sunken lesions on the middle vein, petiole, and stem. Based on the differential reactions of several Brassica spp. and radish cultivars, the leaf spot isolates were divided into three races, with races 1 and 3 predominating. A differential series was established to determine the race-type of isolates and a gene-for-gene model based on the interaction of two avirulence genes in the pathogen races and two matching resistance genes in the differential hosts is proposed. Repetitive-DNA polymerase chain reaction-based fingerprinting was used to assess the genetic diversity of the leaf spot isolates and isolates of closely related Xanthomonas pathovars. Although there was variability within each race, the leaf spot isolates were clustered separately from the X. campestris pv. campestris isolates. We propose that X. campestris isolates that cause a nonvascular leaf spot disease on Brassica spp. should be identified as pv. raphani and not pv. armoraciae. Race-type strains and a neopathotype strain for X. campestris pv. raphani are proposed.

Variational mixture of Bayesian independent component analyzers.

There has been growing interest in subspace data modeling over the past few years. Methods such as principal component analysis, factor analysis, and independent component analysis have gained in popularity and have found many applications in image modeling, signal processing, and data compression, to name just a few. As applications and computing power grow, more and more sophisticated analyses and meaningful representations are sought. Mixture modeling methods have been proposed for principal and factor analyzers that exploit local gaussian features in the subspace manifolds. Meaningful representations may be lost, however, if these local features are nongaussian or discontinuous. In this article, we propose extending the gaussian analyzers mixture model to an independent component analyzers mixture model. We employ recent developments in variational Bayesian inference and structure determination to construct a novel approach for modeling nongaussian, discontinuous manifolds. We automatically determine the local dimensionality of each manifold and use variational inference to calculate the optimum number of ICA components needed in our mixture model. We demonstrate our framework on complex synthetic data and illustrate its application to real data by decomposing functional magnetic resonance images into meaningful-and medically useful-features.

EEG signal processing in anaesthesia. Use of a neural network technique for monitoring depth of anaesthesia.

BACKGROUND: The Bispectral Index (BIS) is a proprietary index of anaesthesia depth, which is correlated with the level of consciousness and probability of intraoperative recall. The present study investigates the use of a neural network technique to obtain a non-proprietary index of the depth of anaesthesia from the processed EEG data. METHODS: Two hundred patients, who underwent general abdominal surgery, were recruited for our trial. For anaesthesia we used a total i.v. technique, tracheal intubation, and artificial ventilation. Fourteen EEG variables, including the BIS, were extracted from the EEG, monitored with an EEG computerized monitor, and then stored on a computer. Data from 150 patients were used to train the neural network. All the variables, excluding the BIS, were used as input data in the neural network. The output targets of the network were provided by anaesthesia scores ranging from 10 to 100 assigned by the anaesthesiologist according to the observer's assessment of alertness and sedation (OAA/S) and other clinical means of assessing depth of anaesthesia. Data from the other 50 patients were used to test the model and for statistical analysis. RESULTS: The artificial neural network was successfully trained to predict an anaesthesia depth index, the NED (neural network evaluated depth), ranging from 0 to 100. The correlation coefficient between the NED and the BIS over the test set was 0.94 (P<0.0001). CONCLUSION: We have developed a neural network model, which evaluates 13 processed EEG parameters to produce an index of anaesthesia depth, which correlates very well with the BIS during total i.v. anaesthesia with propofol.

Sources and Origin of Resistance to Xanthomonas campestris pv. campestris in Brassica Genomes.

ABSTRACT Two hundred and seventy-six accessions of mainly Brassica spp. were screened for resistance to Xanthomonas campestris pv. campestris races. In Brassica oleracea (C genome), the majority of accessions were susceptible to all races, but 43% showed resistance to one or more of the rare races (2, 3, 5, and 6) and a single accession showed partial resistance to races 1, 3, 5, and 6. Further searches for resistance to races 1 and 4, currently the most important races worldwide, and race 6, the race with the widest host range, were made in accessions representing the A and B genomes. Strong resistance to race 4 was frequent in B. rapa (A genome) and B. napus (AC genome), indicating an A genome origin. Resistance to races 1 and 4 was present in a high proportion of B. nigra (B genome) and B. carinata (BC genome) accessions, indicating a B genome origin. B. juncea (AB genome) was the most resistant species, showing either strong resistance to races 1 and 4 or quantitative resistance to all races. Potentially race-nonspecific resistance was also found, but at a lower frequency, in B. rapa, B. nigra, and B. carinata. The combination of race-specific and race-nonspecific resistance could provide durable control of black rot of crucifers.

The recovery of Senegalese African blacks from intravenous anesthesia with propofol and remifentanil is slower than that of Caucasians.

UNLABELLED: Differences in sensitivity to anesthetic drugs have already been described among races. This study was designed to comparatively investigate the anesthetic requirements of two different ethnic groups: Caucasians and African blacks. Forty-five Caucasians from Italy and 45 African blacks from Senegal, who underwent general IV anesthesia with propofol and remifentanil, were comparatively evaluated for anesthetic depth and time lapsed before recovery. We used an electroencephalographic-derived index of depth of anesthesia, the bispectral index (BIS), and evaluation of clinical variables to assess the depth of anesthesia and the recovery trend. Mean BIS values from Caucasians after propofol discontinuation returned to baseline (92-100) in approximately 8 min, whereas in African blacks BIS values remained <80 for some 30 min. Time to eye opening was 10.6 +/- 4.8 min in Caucasians versus 16.9 +/- 8.8 min in African blacks (P < 0.001). Time to respond to loud verbal commands was 14.8 +/- 9.1 min in African blacks versus 9.1 +/- 4.2 min in Caucasians (P < 0.01). During anesthetic induction, the mean arterial pressure decreased by 20% in Caucasians and by only 10% in African blacks. We conclude that the recovery from general anesthesia with propofol was slower in African blacks compared with Caucasian patients. IMPLICATIONS: This study demonstrates statistically significant differences between Caucasians and African blacks in the arousal time from IV anesthesia with propofol and remifentanil. The authors conclude that the recovery from general anesthesia was slower in African blacks compared with Caucasian patients.

The incidence of dieting amongst adolescent girls: a question of interpretation?

AIM: It is the intention of this study establish the extent of dieting practices amongst adolescent girls and identify their perceptions with regard to 'dieting' and 'healthy eating'. METHODS: A total of 140 girls, aged 12-13 years, were recruited from two schools. A self-reported questionnaire, which determined the incidence of dieting and sought to identify the girls' perceptions of 'dieting' and 'healthy eating', was used to collect data. RESULTS: Out of the total group, 33.6% reported that they had dieted at some time and 15.8% were presently dieting. The most popular definition of dieting amongst the dieters was 'eating less/cutting down'; however, the second most popular answer was 'eating healthy food' which was the most popular answer amongst the non-dieters. The most popular definition of healthy eating was 'increasing fruit/ veg/salads', which is similar to how many girls perceived dieting, i.e. eating healthy food (fruit/veg/salads). CONCLUSION: Establishing the actual incidence of dieting amongst adolescent girls is not a clear-cut issue as it can be interpreted in many different ways, depending on the perceptions of the individual. The results of this study showed that in many cases 'dieting' and 'healthy eating' were perceived in a similar light, concluding that the dietary intake of dieters may be similar to that of non-dieters with both groups being at risk from any related health problems.

Cancer-related risk indicators and preventive screening behaviors among lesbians and bisexual women.

OBJECTIVES: This study examined whether lesbians are at increased risk for certain cancers as a result of an accumulation of behavioral risk factors and difficulties in accessing health care. METHODS: Prevalence estimates of behavioral risk factors (nulliparity, obesity, smoking, and alcohol use), cancer screening behaviors, and self-reported breast cancer histories derived from 7 independently conducted surveys of lesbians/bisexual women (n = 11,876) were compared with national estimates for women. RESULTS: In comparison with adjusted estimates for the US female population, lesbians/bisexual women exhibited greater prevalence rates of obesity, alcohol use, and tobacco use and lower rates of parity and birth control pill use. These women were also less likely to have health insurance coverage or to have had a recent pelvic examination or mammogram. Self-reported histories of breast cancer, however, did not differ from adjusted US female population estimates. CONCLUSIONS: Lesbians and bisexual women differ from heterosexual women in patterns of health risk. These women would be expected to be at especially greater risk for chronic diseases linked to smoking and obesity.

Identification and Origin of Xanthomonas campestris pv. campestris Races and Related Pathovars.

ABSTRACT One hundred sixty-four isolates of Xanthomonas campestris pv. campestris and other X. campestris pathovars known to infect cruciferous hosts (X. campestris pvs. aberrans, raphani, armoraciae, and incanae) were inoculated onto a differential series of Brassica spp. to determine both pathogenicity to brassicas and race. Of these, 144 isolates were identified as X. campestris pv. campestris and grouped into six races, with races 1 (62%) and 4 (32%) being predominant. Other races were rare. The remaining 20 isolates from brassicas and other cruciferous hosts were either nonpathogenic or very weakly pathogenic on the differential series and could not be race-typed. Five of these isolates, from the ornamental crucifers wallflower (Cheiranthus cheiri), stock (Matthiola incana) and candytuft (Iberis sp.), showed clear evidence of pathovar-like specificity to the hosts of origin. A gene-for-gene model based on the interaction of four avirulence genes in X. campestris pv. campestris races and four matching resistance genes in the differential hosts is proposed. Knowledge of the race structure and worldwide distribution of races is fundamental to the search for sources of resistance and for the establishment of successful resistance breeding programs.

Lesbian health research: a review and recommendations for future research.

Prior to 1990 lesbians were "invisible" in health care research. Researchers who asked questions specifically about lesbian health concerns were rare, and the burgeoning research on women's health seldom included variables that measured sexual orientation or behavior. In the last decade, however, lesbian health has emerged as a major area of study. A 1999 Institute of Medicine (IOM) report on Lesbian Health has outlined the challenges and gaps in this area of research and has called for focus and funding on specific areas of need. In this article I review research on lesbian health, discuss methodological issues specific to this area of research, and summarize the recommendations of the IOM report.