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Radiochronometry is an important tool for nuclear forensic analysis. Plutonium has a wide array of parent/progeny pairs that can be measured to provide multiple model ages for interpretation. Various methods have been developed to provide data within specified timescales, to varied precision and accuracy requirements. In contrast to uranium, no radiochronometry reference standards currently exist for these measurements and we rely on traceability to activity and isotopic certified materials. A test reference material was provided for a blind laboratory analysis. We present analysis of this material by current techniques to increase confidence to the suitability of this methodology for certification.

The radiochronometric model age is an important signature in nuclear forensic analysis. Recent studies have illustrated the need for controlled experiments on the behavior of decay products during uranium metal casting to provide a foundation for interpretation of discordant model ages. A variety of uranium metal and alloy samples cast under known conditions were analysed by three laboratories. This work is the first multi-laboratory study of its kind to explore how these progeny isotopes are chemically fractionated from uranium metal during casting. The intercomparison allowed for capability demonstration and method development on samples and provided data to increase our understanding of the behavior of decay progeny in these complex systems.

Pharmaceutical management of HIV infection is complex, and proper adherence to antiretroviral regimens is contingent on active patient involvement in treatment. We examined the relationship between patient understanding of HIV and its treatment and health literacy. Structured interviews were conducted with 157 HIV-infected individuals receiving care at a community-based clinic in Shreveport, Louisiana, USA. In all, 48% of patients were reading below a 9th grade level. One-third of patients could not name their HIV medications and this was significantly related to low literacy (P < 0.01). Two-thirds of those reading below the 9th grade level did not know how to take their medications correctly (P < 0.05), and 75% did not know the meaning of a CD4 count or viral load (P < 0.001). Patients with low literacy skills were more likely to state that their physician was their sole source of HIV information (P < 0.005). Physicians may require training to appropriately convey health information to patients of low literacy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene–drug interactions between NSAID use and polymorphisms in COX1 , COX2 , ODC , UGT1A6 and CYP2C9 on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the COX1 Pro17Leu polymorphism ( P =0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene–drug interactions for COX1 Pro17Leu. Statistically significant interactions have also been reported for ODC (315G>A), UGT1A6 (Thr181Ala+Arg184Ser or Arg184Ser alone), and CYP2C9 ( * 2/ * 3). No statistically significant interactions have been reported for polymorphisms in COX2 ; however, an interaction with COX2 −765G>C approached significance ( P =0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for COX1 , COX2 and ODC gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID–gene interactions to date is limited. Reliable detection of gene–NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies.

Current treatment for patients with chronic hepatitis C virus (HCV) infection consists of the combination of pegylated interferon and ribavirin. This treatment regimen achieves a sustained virological response, defined as undetectable HCV RNA 6 months after treatment cessation, in 50% of patients overall. There is therefore a need for new treatments to improve the sustained virological response rate and reduce the number of adverse effects associated with pegylated interferon and ribavirin. This review examines the current management of chronic HCV infection, including who is eligible for treatment, the optimum duration of treatment, and management of side effects. New drugs in development, such as HCV-specific protease inhibitors, polymerase inhibitors, immune modulators and ribavirin analogues, are outlined, and their role in the treatment armamentarium is discussed, whether used alone or in combination with existing treatments.

Because of the recent lack of availability of streptomycin—currently considered the drug of choice for the treatment of tularemia—we reviewed the literature on alternative drugs that have been used for this purpose. In addition, we reviewed data on the in vitro susceptibility of Francisella tularensis to a wide variety of agents. The rate of cure for streptomycin was 97%, with no relapses. For gentamicin and tetracycline, respectively, the rates of cure were 86% and 88%, the rates of relapse were 6% and 12%, and the rates of failure were 8% and 0. The duration of therapy with gentamicin and a delay in its initiation may have affected outcome in severe cases. For chloramphenicol and tobramycin, cure rates were 77% and 50%, respectively; relapse rates were 21 % and 0; and failure rates were 2% and 33%, respectively. Treatment with imipenem/cilastatin was successful in one case, and that with ciprofloxacin or norfloxacin was successful in six cases; in contrast, therapy with ceftriaxone was ineffective in eight cases. On the basis of this review, we conclude that gentamicin is an acceptable alternative to streptomycin for the treatment of tularemia.

Tularemia, an infection caused by the coccobacillus Francisella tularensis, can be a difficult disease process to diagnose and treat. The difficulty in treating this disease is related to the pathophysiology of the infection and the toxicity of the antimicrobial agents presently recommended for treatment. Recent in vitro data have suggested that antimicrobial drugs other than standard agents (streptomycin, gentamicin, chloramphenicol, or tetracycline) may be effective. We present eight cases of documented failure of outpatient use of ceftriaxone in the treatment of tularemia. Our data suggest that while ceftriaxone may have excellent MICs in vitro, these MICs do not necessarily correlate with successful in vivo outcomes.

IntroductionLiver transplantation (LTx) is the only curative therapeutic modality for patients with end-stage liver disease (ESLD). A detailed evaluation of the liver transplant patient is critical to identify patients most likely to benefit from LTx in an era of organ donor shortage to optimise use of a scarce resource.AimThe aim of this study was to analyse the profile and outcome of LTx referrals in a ‘hub and spoke’ LTx service.MethodA retrospective study of all patients referred to the South West Liver Unit, liver transplant service between April 2007 and April 2011. Patients with acute liver failure were excluded from the analysis. Pre-transplant and post-operative follow-up was performed at the South West Liver Unit. All operations were performed at King's College Hospital, London. Pre-LTx demographic and laboratory data were analysed using descriptive methods. Comparisons (Mann–Whitney) and survival (Kaplan–Meier) were estimated. α level of 0.05 was accepted as significant.Results191 consecutive patients (n=128, 67% males) underwent elective pretransplant assessment and posttransplant management. Mean age was 53 years, SD 10.3 (range 19–70). Currently, 9.4% (18/191) patients are under assessment, 10.5% (20/191) are on the waiting list for LTx, 29.8% (57/191) have been transplanted, 7.9% (15/191) died on the list and 42.4% (81/191) were assessed but not listed (too advanced disease in 12%, not fulfilling minimal listing criteria 14.7% and contraindicated 15.7%). Among patients who met minimal listing indications 21% (n=19) were diagnosed with hepatocellular carcinoma (chronic HCV infection or/and alcohol background), 30% (n=28) had alcoholic liver disease, 9% (n=8)—chronic HCV infection, 11% (n=10) exhibit both alcohol and viral aetiology, 4% (n=4)—autoimmune hepatitis, 11% (n=10) - PBC/PSC, 4% NASH (n=4), 2% (n=2) cryptogenic cirrhosis and in 9% (n=8) rare diseases (vascular, metabolic, congenital or chronic rejection). These proportions did not deviate from the whole assessed cohort. Mean UKELD, MELD and CTP scores of all assessed patients were 52 (SD 5.2), 12 (SD 5.6) and 8 (SD 1.9). UKELD correlated strongly with MELD and CTP (Spearman's ρ 0.68 and 0.72, p<0.01) and was slightly higher in listed for LTx group. CTP score did not differ between transplanted and not transplanted patients. Among the liver recipients 36% were blood group A, 12% B, 10% AB and 42% O, similar to the distribution in the whole group. Mean BMI was 26.2, not different between transplanted and not listed patients. However, a third of all assessed patients had severe protein malnutrition, evaluated with hand dynamometry and estimated energy expenditure/intake ratio. The prevalence of HPS and PPH were 9% (11/122) and 3% (4/135) respectively. Three months-, 1- and 3-year survival of the patients and the grafts were 98%/97%/97% and 98%/95%/90%. Abstract P80 figure 1 illustrates the differences in survival of transplanted and not transplanted patients.Abstract P80 Figure 1Survival of all patients.ConclusionGraft and patient survival in the ‘hub and spoke’ model is good. Alcohol and hepatoma are the commonest reasons for listing. Protein malnutrition is common in this patient cohort suggesting improved patient nutrition and early dietician involvement is needed.

[...]we would contend that genotype and patient age should be incorporated into any algorithm as should factors known to accelerate the natural history of the disease including: co-infection with human immunodeficiency virus (HIV), alcohol excess, obesity, and male gender. 2 Patients with a liver stiffness measurement between 6 and 12 kPa are likely to receive treatment and do not need long-term follow-up should SVR be achieved, so why subject these patients to biopsy?

Multiple myeloma related amyloidosis is rare and its presentation with subacute liver failure (SALF) has not been reported. A case is described of a 46 year old woman presenting with a six week history of nausea, abdominal pain, and jaundice. Routine tests failed to establish a cause. Computed tomography showed a small volume liver consistent with SALF. Emergency liver transplantation was not undertaken because of the suspicion of underlying malignancy. At necropsy, liver biopsy showed amyloid deposition and bone marrow biopsy showed multiple myeloma. Thus, amyloidosis should be added to the list of potential causes of SALF.