Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report

This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic valve replacement was prescribed high-dose ketoconazole and hydrocortisone for the treatment of prostate cancer. Despite lowering the warfarin dosage by 35% during the start of high dose ketoconazole, an additional dose reduction was required subsequently when the INR rose from 2.62 to 3.82 within nine days. After a total dose reduction of 43%, the INR returned to therapeutic range within two weeks. The Naranjo probability scale revealed a probable adverse reaction of increased anticoagulant effect associated with high dose ketoconazole. Due to the inhibition of warfarin metabolism by ketoconazole, patients taking high dose ketoconazole concomitantly with warfarin may need their warfarin dosage reduced by more than is currently recommended, as well as receive more frequent INR monitoring to avoid over anticoagulation

The burden of mental health in lymphatic filariasis.

BACKGROUND Neglected Tropical Diseases (NTDs) afflict around one billion individuals in the poorest parts of the world with many more at risk. Lymphatic filariasis is one of the most prevalent of the infections and causes significant morbidity in those who suffer the clinical conditions, particularly lymphedema and hydrocele. Depressive illness has been recognised as a prevalent disability in those with the disease because of the stigmatising nature of the condition. No estimates of the burden of depressive illness of any neglected tropical disease have been undertaken to date despite the recognition that such diseases have major consequences for mental health not only for patients but also their caregivers. METHODS We developed a mathematical model to calculate the burden of Disability- Adjusted Life Years (DALY) attributable to depressive illness in lymphatic filariasis and that of their caregivers using standard methods for calculating DALYs. Estimates of numbers with clinical disease was based on published estimates in 2012 and the numbers with depressive illness from the available literature. RESULTS We calculated that the burden of depressive illness in filariasis patients was 5.09 million disability-adjusted life years (DALYs) and 229,537 DALYs attributable to their caregivers. These figures are around twice that of 2.78 million DALYs attributed to filariasis by the Global Burden of Disease study of 2010. CONCLUSIONS Lymphatic filariasis and other neglected tropical diseases, notably Buruli Ulcer, cutaneous leishmaniasis, leprosy, yaws, onchocerciasis and trachoma cause significant co morbidity associated with mental illness in patients. Studies to assess the prevalence of the burden of this co-morbidity should be incorporated into any future assessment of the Global Burden of neglected tropical diseases. The prevalence of depressive illness in caregivers who support those who suffer from these conditions is required. Such assessments are critical for neglected tropical diseases which have such a huge global prevalence and thus will contribute a significant burden of co-morbidity attributable to mental illness

Incident Notification Process as BPaaS for Electicity Supply Systems

Business Process Management (BPM) systems have been deployed in many large organizations to improve their business effectiveness and efficiency. Cloud based BPM systems have provided SMEs using BPM in a pay-per-use manner. Previous work has focused on looking at cloud based BPM from the perspectives of distribution of data, activity or/and business engine and related issues, such as scalability of system, security of data, distribution of data and activities. To achieve business agility business process collaboration needs to seamlessly connect local BPM systems and cloud based BPM systems. In this paper we look at BPM in the cloud from a new user perspective, how process models can be handled in the cloud for the fast pace of change of business collaborations. The paper proposes a distribution solution in which at the design time, the shared process model can be discovered from a process repository, and adapted to local needs; at run-time a process is distributed. A real world case is used to explain our design and implementation. Collaborative process for incident notifications is built to work across different organizations

Treatment of bleeding in patients with liver disease

Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure-related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post-procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis

Extensive ethnolinguistic diversity in Vietnam reflects multiple sources of genetic diversity

Vietnam features extensive ethnolinguistic diversity and occupies a key position in Mainland Southeast Asia (MSEA). Yet, the genetic diversity of Vietnam remains relatively unexplored, especially with genome-wide data, because previous studies have focused mainly on the majority Kinh group. Here we analyze newly-generated genome-wide SNP data for the Kinh and 21 additional ethnic groups in Vietnam, encompassing all five major language families in MSEA. In addition to analyzing the allele and haplotype sharing within the Vietnamese groups, we incorporate published data from both nearby modern populations and ancient samples for comparison. In contrast to previous studies that suggested a largely indigenous origin for Vietnamese genetic diversity, we find that Vietnamese ethnolinguistic groups harbor multiple sources of genetic diversity that likely reflect different sources for the ancestry associated with each language family. However, linguistic diversity does not completely match genetic diversity: there have been extensive interactions between the Hmong-Mien and Tai-Kadai groups; different Austro-Asiatic groups show different affinities with other ethnolinguistic groups; and we identified a likely case of cultural diffusion in which some Austro-Asiatic groups shifted to Austronesian languages during the past 2,500 years. Overall, our results highlight the importance of genome-wide data from dense sampling of ethnolinguistic groups in providing new insights into the genetic diversity and history of an ethnolinguistically-diverse region, such as Vietnam

Cathodoluminescence as a method of extracting detailed information from nanophotonics systems: a study of silicon nanocrystals

We investigated Si nanocaystal samples produced by high dose 600 keV Si+ implantation of fused silica and annealing using cathodoluminescence (CL). CL spectra collected under 5-25 keV electron irradiation show similar features to reported photoluminescenc

Directional Soliton and Breather Beams

Solitons and breathers are nonlinear modes that exist in a wide range of physical systems. They are fundamental solutions of a number of nonlinear wave evolution equations, including the uni-directional nonlinear Schr\"odinger equation (NLSE). We report the observation of slanted solitons and breathers propagating at an angle with respect to the direction of propagation of the wave field. As the coherence is diagonal, the scale in the crest direction becomes finite, consequently, a beam dynamics forms. Spatio-temporal measurements of the water surface elevation are obtained by stereo-reconstructing the positions of the floating markers placed on a regular lattice and recorded with two synchronized high-speed cameras. Experimental results, based on the predictions obtained from the (2D+1) hyperbolic NLSE equation, are in excellent agreement with the theory. Our study proves the existence of such unique and coherent wave packets and has serious implications for practical applications in optical sciences and physical oceanography. Moreover, unstable wave fields in this geometry may explain the formation of directional large amplitude rogue waves with a finite crest length within a wide range of nonlinear dispersive media, such as Bose-Einstein condensates, plasma, hydrodynamics and optics

SiON integrated optics elliptic couplers for Fizeau-based Optical Coherence Tomography

The use of integrated optics for Optical Coherence Tomography (OCT) can offer significant cost reductions and new applications. We designed, fabricated, and characterized Silicon oxynitride (SiON) elliptic couplers that are used to focus light from a chip into the off-chip environment. Fizeau-based OCT measurements are performed and compared to calculations

Dominant male song performance reflects current immune state in a cooperatively breeding songbird.

Conspicuous displays are thought to have evolved as signals of individual "quality", though precisely what they encode remains a focus of debate. While high quality signals may be produced by high quality individuals due to "good genes" or favourable early-life conditions, whether current immune state also impacts signalling performance remains poorly understood, particularly in social species. Here, we experimentally demonstrate that male song performance is impaired by immune system activation in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). We experimentally activated the immune system of free-living dominant males via subcutaneous injection of phytohemagglutinin (PHA) and contrasted its effects with those of a control (phosphate buffered saline) injection. PHA-challenged males showed significant reductions in both the duration and the rate of their song performance, relative to controls, and this could not be readily attributed to effects of the challenge on body mass, as no such effects were detected. Furthermore, male song performance prior to immune-challenge predicted the scale of the inflammatory response to the challenge. Our findings suggest that song performance characteristics are impacted by current immune state. This link between current state and signal performance might therefore contribute to enforcing the honesty of signal performance characteristics. Impacts of current state on signaling may be of particular importance in social species, where subordinates may benefit from an ability to identify and subsequently challenge same-sex dominants in a weakened state