The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

Risk of cardiovascular and all-cause mortality: impact of impaired health-related functioning and diabetes: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study.

OBJECTIVE: There is an established link between health-related functioning (HRF) and cardiovascular disease (CVD) mortality, and it is known that those with diabetes predominantly die of CVD. However, few studies have determined the combined impact of diabetes and impaired HRF on CVD mortality. We investigated whether this combination carries a higher CVD risk than either component alone. RESEARCH DESIGN AND METHODS: The Australian Diabetes, Obesity and Lifestyle (AusDiab) study included 11,247 adults aged ≥ 25 years from 42 randomly selected areas of Australia. At baseline (1999-2000), diabetes status was defined using the World Health Organization criteria and HRF was assessed using the SF-36 questionnaire. RESULTS: Overall, after 7.4 years of follow-up, 57 persons with diabetes and 105 without diabetes had died from CVD. In individuals with and without diabetes, HRF measures were significant predictors of increased CVD mortality. The CVD mortality risks among those with diabetes or impaired physical health component summary (PCS) alone were similar (diabetes only: hazard ratio 1.4 [95% CI 0.7-2.7]; impaired PCS alone: 1.5 [1.0-2.4]), while those with both diabetes and impaired PCS had a much higher CVD mortality (2.8 [1.6-4.7]) compared with those without diabetes and normal PCS (after adjustment for multiple covariates). Similar results were found for the mental health component summary. CONCLUSIONS: This study demonstrates that the combination of diabetes and impaired HRF is associated with substantially higher CVD mortality. This suggests that, among those with diabetes, impaired HRF is likely to be important in the identification of individuals at increased risk of CVD mortality

Anatomy of terminal moraine segments and implied lake stability on Ngozumpa Glacier, Nepal, from electrical resistivity tomography (ERT)

This research was supported financially by the European Commission FP7-MC-IEF (PIEF-GA-2012-330805), the University Centre in Svalbard (UNIS), National Geographic Society GRANT #W135-10.Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common and pose significant outburst flood hazards if the dam is breached. While moraine subsurface structure and internal processes are likely to influence dam stability, only few sites have so far been investigated. We conducted electrical resistivity tomography (ERT) surveys at two sites on the terminal moraine complex of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability. The resistivity signature of glacier ice at the site (100-15 kΩ m) is more consistent with values measured from cold glacier ice and while this may be feasible, uncertainties in the data inversion introduce ambiguity to this thermal interpretation. However, the ERT data does provide a significant improvement to our knowledge of the subsurface characteristics at these sites, clearly showing the presence (or absence) of glacier ice. Our interpretation is that of a highly complex latero-terminal moraine, resulting from interaction between previous glacier advance, recession and outburst flooding. If the base-level Spillway Lake continues to expand to a fully formed moraine-dammed glacial lake, the degradation of the ice core could have implications for glacial lake outburst risk.Publisher PDFPeer reviewe

Songs between cities: Listening to courtesans in colonial north India

In the aftermath of 1857, urban spaces and cultural practices were transformed and contested. Regional royal capitals became nodes in a new colonial geography, and the earlier regimes that had built them were recast as decadent and corrupt societies. Demolitions and new infrastructures aside, this transformation was also felt at the level of manners, sexual mores, language politics, and the performing arts. This article explores this transformation with a focus on women's language, female singers and dancers, and the men who continued to value their literary and musical skills. While dancing girls and courtesans were degraded by policy-makers and vernacular journalists alike, their Urdu compositions continued to be circulated, published, and discussed. Collections of women's biographies and lyrics gesture to the importance of embodied practices in cultivating emotional positions. This cultivation was valued in late Mughal elite society, and continued to resonate for emotional communities of connoisseurs, listeners, and readers, even as they navigated the expectations and sensibilities of colonial society

Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified

A multi-disciplinary perspective on emergent and future innovations in peer review [version 2; referees: 2 approved]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

The role of microRNAs in defining LSECs cellular identity and in regulating F8 gene expression

Introduction: Coagulation Factor VIII (FVIII) plays a pivotal role in the coagulation cascade, and deficiencies in its levels, as seen in Hemophilia A, can lead to significant health implications. Liver sinusoidal endothelial cells (LSECs) are the main producers and contributors of FVIII in blood, a fact we have previously elucidated through mRNA expression profiling when comparing these cells to other endothelial cell types.Methods: Our current investigation focuses on small microRNAs, analyzing their distinct expression patterns across various endothelial cells and hepatocytes.Results: The outcome of this exploration underscores the discernible microRNAs expression differences that set LSECs apart from both hepatocytes (193 microRNAs at p < 0.05) and other endothelial cells (72 microRNAs at p < 0.05). Notably, the 134 and 35 overexpressed microRNAs in LSECs compared to hepatocytes and other endothelial cells, respectively, shed light on the unique functions of LSECs in the liver.Discussion: Our investigation identified a panel of 10 microRNAs (miR-429, miR-200b-3p, miR-200a-3p, miR-216b-5p, miR-1185-5p, miR-19b-3p, miR-192-5p, miR-122-5p, miR-30c-2-3p, and miR-30a-5p) that distinctly define LSEC identity. Furthermore, our scrutiny extended to microRNAs implicated in F8 regulation, revealing a subset (miR-122-5p, miR-214-3p, miR-204-3p, and miR-2682-5p) whose expression intricately correlates with F8 expression within LSECs. This microRNA cohort emerges as a crucial modulator of F8, both directly through suppression and indirect effects on established F8-related transcription factors. The above microRNAs emerged as potential targets for innovative therapies in Hemophilia A patients

CO2 storage in depleted gas reservoirs: A study on the effect of residual gas saturation

Depleted gas reservoirs are recognized as the most promising candidate for carbon dioxide storage. Primary gas production followed by injection of carbon dioxide after depletion is the strategy adopted for secondary gas recovery and storage practices. This strategy, however, depends on the injection strategy, reservoir characteristics and operational parameters. There have been many studies to-date discussing critical factors influencing the storage performance in depleted gas reservoirs while little attention was given to the effect of residual gas. In this paper, an attempt was made to highlight the importance of residual gas on the capacity, injectivity, reservoir pressurization, and trapping mechanisms of storage sites through the use of numerical simulation. The results obtained indicated that the storage performance is proportionally linked to the amount of residual gas in the medium and reservoirs with low residual fluids are a better choice for storage purposes. Therefore, it would be wise to perform the secondary recovery before storage in order to have the least amount of residual gas in the medium. Although the results of this study are useful to screen depleted gas reservoirs for the storage purpose, more studies are required to confirm the finding presented in this paper