Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications : Report of 5 cases and review of literature

Heparin is one of the most frequently used anticoagulants. It is easy to use, but can be associated with life-threatening side effects. One of these is heparin-induced thrombocytopenia syndrome (HITS), which develops in about 3–5% of patients exposed to heparin and is associated with thrombosis in 1% of cases. We report here the successful treatment of five patients with HITS who were treated with alternative anticoagulants namely danaparoid or hirudin. The median time between their exposure to heparin and onset of symptoms and or signs was 10.2 days (range 7–14 days). Platelet counts decreased to a mean of 38.4 x 109 /l (12–82 x 109/l). All five patients had evidence of thrombosis; four patients had clinical and radiological evidence of pulmonary emboli, one patient had confirmed deep vein thrombosis (DVT) and one patient had extensive skin necrosis of the thighs and abdomen. Platelet aggregation test were positive in two patients, inconclusive in one patient and negative in two patients. Two patients were anticoagulated with danaparoid and three with hirudin until their platelet counts returned to normal between 4 and 14 days (average 6 days) following the recognition of the syndrome. Our patients had significant morbidity, but no mortality. Immediate withdrawal of heparin is of paramount importance and introduction of alternative anticoagulant is necessary in the presence of thrombosis

Animal movement modelling: Independent or dependent models?

Hidden Markov models have become a popular time series method for the analysis of GPS tracked animals. Their advantage for identifying latent behavioural states compared with Independent Mixture models is that they take into account the time series dependency of successive displacement distances by the tracked animals. However, little is known about how the analysis results may differ depending on which of these approaches is used. We compared the results and interpretations obtained from fitting Hidden Markov and Independent Mixture models to simulated movement data as well as to field data recording the hourly movements of sable antelope and buffalo within the Kruger National Park, South Africa. Hidden Markov models consistently yielded narrower confidence intervals around parameters and smaller standard errors than simpler time independent mixture models, but for some data the improvement was marginal and the Independent Mixture model provided an adequate alternative for identifying the latent behavioural states of the animal. In general, it is expected Hidden Markov models will provide the better balance between model complexity and extensibility for animal movement modelling from a statistical perspective. However, in some cases, Independent Mixture models could provide an adequate alternative method and might be more faithful biologically

Determinants of physician networks: an ethnographic study examining the processes that inform patterns of collaboration and referral decision-making among physicians

Objective Most scholarly attention to studying collaborative ties in physician networks has been devoted to quantitatively analysing large, complex datasets. While valuable, such studies can reduce the dynamic and contextual complexities of physician collaborations to numerical values. Qualitative research strategies can contribute to our understanding by addressing the gaps left by more quantitative approaches. This study seeks to contribute to the literature that applies network science approaches to the context of healthcare delivery. We use qualitative, observational and interview, methods to pursue an in-depth, micro-level approach to the deeply social and discursive processes that influence patterns of collaboration and referral decision-making in physician networks. Design Qualitative methodologies that paired ethnographic field observations, semistructured interviews and document analysis were used. An inductive thematic analysis approach was used to analyse, identify and describe patterns in those data. Setting This study took place in a high-volume cardiovascular department at a major academic medical centre (AMC) located in the Midwest region of the USA. Participants Purposive and snowballing sampling were used to recruit study participants for both the observational and face-to-face in-depth interview portions of the study. In total, 25 clinicians and 43 patients participated in this study. Results Two primary thematic categories were identified: (1) circumstances for external engagement; and (2) clinical conditions for engagement. Thematic subcategories included community engagement, scientific engagement, reputational value, experiential information, professional identity, self-awareness of competence, multidisciplinary programmes and situational factors. Conclusion This study adds new contextual knowledge about the mechanisms that characterise referral decision-making processes and how these impact the meaning of physician relationships, organisation of healthcare delivery and the knowledge and beliefs that physicians have about their colleagues. This study highlights the nuances that influence how new collaborative networks are formed and maintained by detailing how relationships among physicians develop and evolve over time

Network Hawkes Process Models for Exploring Latent Hierarchy in Social Animal Interactions

Group-based social dominance hierarchies are of essential interest in animal behavior research. Studies often record aggressive interactions observed over time, and models that can capture such dynamic hierarchy are therefore crucial. Traditional ranking methods summarize interactions across time, using only aggregate counts. Instead, we take advantage of the interaction timestamps, proposing a series of network point process models with latent ranks. We carefully design these models to incorporate important characteristics of animal interaction data, including the winner effect, bursting and pair-flip phenomena. Through iteratively constructing and evaluating these models we arrive at the final cohort Markov-Modulated Hawkes process (C-MMHP), which best characterizes all aforementioned patterns observed in interaction data. We compare all models using simulated and real data. Using statistically developed diagnostic perspectives, we demonstrate that the C-MMHP model outperforms other methods, capturing relevant latent ranking structures that lead to meaningful predictions for real data

Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function.

BACKGROUND: Previously we described a system whereby human peripheral blood T cells stimulated for 8 days in a cytokine cocktail acquired effector function for contact-dependent induction of proinflammatory cytokines from monocytes. We termed these cells cytokine-activated (Tck) cells and found that the signalling pathways elicited in the responding monocytes were identical whether they were placed in contact with Tck cells or with T cells isolated from rheumatoid arthritis (RA) synovial tissue. METHODS: Here, using magnetic beads and fluorescence-activated cell sorting, we extensively phenotype the Tck effector cells and conclude that effector function resides within the CD4+CD45RO+, CCR7-, CD49dhigh population, and that these cells are derived from the effector memory CD4+ T cells in resting blood. RESULTS: After stimulation in culture, these cells produce a wide range of T-cell cytokines, undergo proliferation and differentiate to acquire an extensively activated phenotype resembling RA synovial T cells. Blocking antibodies against CD69, CD18, or CD49d resulted in a reduction of tumour necrosis factor-alpha production from monocytes stimulated with CD4+CD45RO+ Tck cells in the co-culture assay. Moreover, blockade of these ligands also resulted in inhibition of spontaneous tumour necrosis factor-alpha production in RA synovial mononuclear cell cultures. CONCLUSION: Taken together, these data strengthen our understanding of T-cell effector function, highlight the multiple involvement of different cell surface ligands in cell-cell contact and, provide novel insights into the pathogenesis of inflammatory RA disease

Expansion of the ligand knowledge base for chelating P,P-donor ligands (LKB-PP)

[Image: see text] We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor ligands (LKB-PP, Organometallics2008, 27, 1372–1383) by 208 ligands and introduced an additional steric descriptor (nHe(8)). This expanded knowledge base now captures information on 334 bidentate ligands and has been processed with principal component analysis (PCA) of the descriptors to produce a detailed map of bidentate ligand space, which better captures ligand variation and has been used for the analysis of ligand properties

Solving the woolly mammoth conundrum: amino acid 15N-enrichment suggests a distinct forage or habitat

Understanding woolly mammoth ecology is key to understanding Pleistocene community dynamics and evaluating the roles of human hunting and climate change in late Quaternary megafaunal extinctions. Previous isotopic studies of mammoths’ diet and physiology have been hampered by the ‘mammoth conundrum’: woolly mammoths have anomalously high collagen δ15N values, which are more similar to coeval carnivores than herbivores and which could imply a distinct diet and (or) habitat, or a physiological adaptation. We analyzed individual amino acids from collagen of adult woolly mammoths and coeval species and discovered greater  15N enrichment in source amino acids of woolly mammoths than in most other herbivores or carnivores. Woolly mammoths consumed an isotopically distinct food source, reflective of extreme aridity, dung fertilization and (or) plant selection. This dietary signal suggests that woolly mammoths occupied a distinct habitat or forage niche relative to other Pleistocene herbivores

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear

How rainfall variation influences reproductive patterns of African Savanna ungulates in an equatorial region where photoperiod variation is absent.

In high temperate latitudes, ungulates generally give birth within a narrow time window when conditions are optimal for offspring survival in spring or early summer, and use changing photoperiod to time conceptions so as to anticipate these conditions. However, in low tropical latitudes day length variation is minimal, and rainfall variation makes the seasonal cycle less predictable. Nevertheless, several ungulate species retain narrow birth peaks under such conditions, while others show births spread quite widely through the year. We investigated how within-year and between-year variation in rainfall influenced the reproductive timing of four ungulate species showing these contrasting patterns in the Masai Mara region of Kenya. All four species exhibited birth peaks during the putative optimal period in the early wet season. For hartebeest and impala, the birth peak was diffuse and offspring were born throughout the year. In contrast, topi and warthog showed a narrow seasonal concentration of births, with conceptions suppressed once monthly rainfall fell below a threshold level. High rainfall in the previous season and high early rains in the current year enhanced survival into the juvenile stage for all the species except impala. Our findings reveal how rainfall variation affecting grass growth and hence herbivore nutrition can govern the reproductive phenology of ungulates in tropical latitudes where day length variation is minimal. The underlying mechanism seems to be the suppression of conceptions once nutritional gains become insufficient. Through responding proximally to within-year variation in rainfall, tropical savanna ungulates are less likely to be affected adversely by the consequences of global warming for vegetation phenology than northern ungulates showing more rigid photoperiodic control over reproductive timing