The changing role of beta-blocker therapy in patients with cirrhosis

SummaryCirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis

DNA identification by pedigree likelihood ratio accommodating population substructure and mutations

DNA typing is an important tool in missing-person identification, especially in mass-fatality disasters. Identification methods comparing a DNA profile from unidentified human remains with that of a direct (from the person) or indirect (for example, from a biological relative) reference sample and ranking the pairwise likelihood ratios (LR) is straightforward and well defined. However, for indirect comparison cases in which several members from a family can serve as reference samples, the full power of kinship analysis is not entirely exploited. Because biologically related family members are not genetically independent, more information and thus greater power can be attained by simultaneous use of all pedigree members in most cases, although distant relationships may reduce the power. In this study, an improvement was made on the method for missing-person identification for autosomal and lineage-based markers, by considering jointly the DNA profile data of all available family reference samples. The missing person is evaluated by a pedigree LR of the probability of DNA evidence under alternative hypotheses (for example, the missing person is unrelated or if they belong to this pedigree with a specified biological relationship) and can be ranked for all pedigrees within a database. Pedigree LRs are adjusted for population substructure according to the recommendations of the second National Research Council (NRCII) Report. A realistic mutation model was also incorporated to accommodate the possibility of false exclusion. The results show that the effect of mutation on the pedigree LR is moderate, but LRs can be significantly decreased by the effect of population substructure. Finally, Y chromosome and mitochondrial DNA were integrated into the analysis to increase the power of identification. A program titled MPKin was developed, combining the aforementioned features to facilitate genetic analysis for identifying missing persons. The computational complexity of the algorithms is explained, and several ways to reduce the complexity are introduced

A prospective cost-benefit analysis for nylon 4N6FLOQSwabs (R) : example of the process and potential benefits

Laboratories and their criminal justice systems are confronted with challenges for implementing new technologies, practices, and policies even when there appears to be demonstrative benefits to operational performance. Impacting decisions are the often higher costs associated with, for example, new technologies, limited current budgets, and making hard decisions on what to sacrifice to take on the seemingly better approach. A prospective cost-benefit analysis (CBA) could help an agency better formulate its strategies and plans and more importantly delineate how a relatively small increase to take on, for example, a new technology can have large impact on the system (e.g., the agency, other agencies, victims and families, and taxpayers). To demonstrate the process and potential value a CBA was performed on the use of an alternate and more expensive swab with reported better DNA yield and being certified human DNA free (i.e., nylon 4N6FLOQSwabs (R)), versus the traditional less costly swab (i.e., cotton swab). Assumptions are described, potential underestimates and overestimates noted, different values applied (for low and modest to high), and potential benefits (monetary and qualitative) presented. The overall outcome is that the cost of using the more expensive technology pales compared with the potential tangible and intangible benefits. This approach could be a guide for laboratories (and associated criminal justice systems) worldwide to support increased funding, although the costs and benefits may vary locally and for different technologies, practices, and policies. With well-developed CBAs, goals of providing the best services to support the criminal justice system and society can be attained.Peer reviewe

Response to: Use of prior odds for missing persons identifications - authors' reply

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Use of prior odds for missing persons identifications

Identification of missing persons from mass disasters is based on evaluation of a number of variables and observations regarding the combination of features derived from these variables. DNA typing now is playing a more prominent role in the identification of human remains, and particularly so for highly decomposed and fragmented remains. The strength of genetic associations, by either direct or kinship analyses, is often quantified by calculating a likelihood ratio. The likelihood ratio can be multiplied by prior odds based on nongenetic evidence to calculate the posterior odds, that is, by applying Bayes' Theorem, to arrive at a probability of identity. For the identification of human remains, the path creating the set and intersection of variables that contribute to the prior odds needs to be appreciated and well defined. Other than considering the total number of missing persons, the forensic DNA community has been silent on specifying the elements of prior odds computations. The variables include the number of missing individuals, eyewitness accounts, anthropological features, demographics and other identifying characteristics. The assumptions, supporting data and reasoning that are used to establish a prior probability that will be combined with the genetic data need to be considered and justified. Otherwise, data may be unintentionally or intentionally manipulated to achieve a probability of identity that cannot be supported and can thus misrepresent the uncertainty with associations. The forensic DNA community needs to develop guidelines for objectively computing prior odds

Prevalence of Dietary Supplement Use in Healthy Pre-School Chinese Children in Australia and China

There is a growing use of dietary supplements in many countries including China. This study aimed to document the prevalence of dietary supplements use and characteristics of Chinese pre-school children using dietary supplements in Australia and China. A survey was carried out in Perth, Western Australia of 237 mothers with children under five years old and 2079 in Chengdu and Wuhan, China. A total of 22.6% and 32.4% of the Chinese children were taking dietary supplements in Australia and China, respectively. In China, the most commonly used dietary supplements were calcium (58.5%) and zinc (40.4%), while in Australia, the most frequently used types were multi-vitamins/minerals (46.2%) and fish oil (42.3%). In Australia, “not working”, “never breastfeed”, “higher education level of the mother” and “older age of the child” were associated with dietary supplement use in children. In China, being unwell and “having higher household income” were significantly related to dietary supplement usage. Because of the unknown effects of many supplements on growth and development and the potential for adverse drug interactions, parents should exercise caution when giving their infants or young children dietary supplements. Wherever possible it is preferable to achieve nutrient intakes from a varied diet rather than from supplements

Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer

Pioneering work in the 1990s first linked a novel microaerobic bacterium, Helicobacter hepaticus, with chronic active hepatitis and inflammatory bowel disease in several murine models. Targeted H. hepaticus infection experiments subsequently demonstrated its ability to induce colitis, colorectal cancer, and extraintestinal diseases in a number of mouse strains with defects in immune function and/or regulation. H. hepaticus is now widely utilized as a model system to dissect how intestinal microbiota interact with the host to produce both inflammatory and tolerogenic responses. This model has been used to make important advances in understanding factors that regulate both acquired and innate immune response within the intestine. Further, it has been an effective tool to help define the function of regulatory T cells, including their ability to directly inhibit the innate inflammatory response to gut microbiota. The complete genomic sequence of H. hepaticus has advanced the identification of several virulence factors and aided in the elucidation of H. hepaticus pathogenesis. Delineating targets of H. hepaticus virulence factors could facilitate novel approaches to treating microbially induced lower bowel inflammatory diseases.National Institutes of Health (U.S.) (grant R01-DK052413)National Institutes of Health (U.S.) (grant P01-CA026731)National Institutes of Health (U.S.) (grant R01-CA067529)National Institutes of Health (U.S.) (grant P30-ES02109)National Institutes of Health (U.S.) (grant R01-A1052267)National Institutes of Health (U.S.) (grantR01-CA108854