Bias, Repeatability and Reproducibility of Liver T1 Mapping With Variable Flip Angles.

BACKGROUND: Three-dimensional variable flip angle (VFA) methods are commonly used for T1 mapping of the liver, but there is no data on the accuracy, repeatability, and reproducibility of this technique in this organ in a multivendor setting. PURPOSE: To measure bias, repeatability, and reproducibility of VFA T1 mapping in the liver. STUDY TYPE: Prospective observational. POPULATION: Eight healthy volunteers, four women, with no known liver disease. FIELD STRENGTH/SEQUENCE: 1.5-T and 3.0-T; three-dimensional steady-state spoiled gradient echo with VFAs; Look-Locker. ASSESSMENT: Traveling volunteers were scanned twice each (30 minutes to 3 months apart) on six MRI scanners from three vendors (GE Healthcare, Philips Medical Systems, and Siemens Healthineers) at two field strengths. The maximum period between the first and last scans among all volunteers was 9 months. Volunteers were instructed to abstain from alcohol intake for at least 72 hours prior to each scan and avoid high cholesterol foods on the day of the scan. STATISTICAL TESTS: Repeated measures ANOVA, Student t-test, Levene's test of variances, and 95% significance level. The percent error relative to literature liver T1 in healthy volunteers was used to assess bias. The relative error (RE) due to intrascanner and interscanner variation in T1 measurements was used to assess repeatability and reproducibility. RESULTS: The 95% confidence interval (CI) on the mean bias and mean repeatability RE of VFA T1 in the healthy liver was 34 ± 6% and 10 ± 3%, respectively. The 95% CI on the mean reproducibility RE at 1.5 T and 3.0 T was 29 ± 7% and 25 ± 4%, respectively. DATA CONCLUSION: Bias, repeatability, and reproducibility of VFA T1 mapping in the liver in a multivendor setting are similar to those reported for breast, prostate, and brain. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Comparison of LI-RADS with other non-invasive liver MRI criteria and radiological opinion for diagnosing hepatocellular carcinoma in cirrhotic livers using gadoxetic acid with histopathological explant correlation.

AIM: To establish the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) and compare its performance to that of international criteria from European Assofor the Study of the Liver (EASL), Japan Society of Hepatology (JSH), Asian Pacific Association for the Study of the Liver (APASL), and Organ Procurement and Transplantation Network (OPTN), and to the reporting radiologist's overall opinion regarding the probability of a nodule being a HCC by correlating with a histological diagnosis from whole liver explants. MATERIALS AND METHODS: The present single-centre, retrospective review selected participants based on the following criteria: adults (≥18 years) listed for liver transplantation in 2014/2015, with liver cirrhosis at the time of magnetic resonance imaging (MRI) with hepatocyte specific contrast agent, and at least one liver lesion ≥10 mm on MRI with histology from subsequent liver explant for comparison. Each lesion was assessed against international criteria and given a "radiologist opinion" score of 1-5 (1 = definitely benign, 5 = definitely HCC). RESULTS: Total 268 patient records were reviewed, with 105 eligible lesions identified from 47 patients. Median lesion size was 15.5 mm (range 10-68 mm). Sensitivity (%), specificity (%), and positive predictive value (PPV; %) for LI-RADS LR5 was 45, 89, and 89, for LI-RADS LR4+5 + TIV was 61, 80, and 86, for EASL was 44, 86 and 86, for JSH/APASL was 64, 81, and 87, for OPTN was 36, 90, and 88, and for "radiologist impression" of probably or definitely HCC was 79, 79, and 88 respectively. CONCLUSIONS: MRI has moderate sensitivity and good specificity for the diagnosis of HCC with considerable variation depending on criteria used. OPTN criteria have the best specificity, but low sensitivity. "Radiologist opinion" gives highest overall accuracy with increases in sensitivity and reduction in specificity when compared to the imaging criteria.

Functional mutants of Azospirillum brasilense elicit beneficial physiological and metabolic responses in Zea mays contributing to increased host iron assimilation.

Iron (Fe), an essential element for plant growth, is abundant in soil but with low bioavailability. Thus, plants developed specialized mechanisms to sequester the element. Beneficial microbes have recently become a favored method to promote plant growth through increased uptake of essential micronutrients, like Fe, yet little is known of their mechanisms of action. Functional mutants of the epiphytic bacterium Azospirillum brasilense, a prolific grass-root colonizer, were used to examine mechanisms for promoting iron uptake in Zea mays. Mutants included HM053, FP10, and ipdC, which have varying capacities for biological nitrogen fixation and production of the plant hormone auxin. Using radioactive iron-59 tracing and inductively coupled plasma mass spectrometry, we documented significant differences in host uptake of Fe2+/3+ correlating with mutant biological function. Radioactive carbon-11, administered to plants as 11CO2, provided insights into shifts in host usage of 'new' carbon resources in the presence of these beneficial microbes. Of the mutants examined, HM053 exhibited the greatest influence on host Fe uptake with increased plant allocation of 11C-resources to roots where they were transformed and exuded as 11C-acidic substrates to aid in Fe-chelation, and increased C-11 partitioning into citric acid, nicotianamine and histidine to aid in the in situ translocation of Fe once assimilated.

Comparison of routine field epidemiology and whole genome sequencing to identify tuberculosis transmission in a remote setting.

Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005-2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

Whole genome sequencing for improved understanding of Mycobacterium tuberculosis transmission in a remote circumpolar region.

Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings - regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005-2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.

Tibial plateau levelling osteotomy locking-compression plates for stabilisation of canine and feline ilial body fractures.

OBJECTIVES: To evaluate the clinical and radiographic outcomes following surgical stabilisation of ilial fractures in dogs and cats using a laterally applied Synthes TPLO locking compression plate. MATERIALS AND METHODS: Medical records and radiographs of seven dogs and two cats which had undergone surgical repair of an ilial body fracture with a TPLO locking compression plate were reviewed. Long-term clinical follow-up was obtained from an owner or referring veterinarian questionnaire. RESULTS: Fracture reduction was anatomic in six of nine ilia and near-anatomic in three of nine. All but one fracture achieved osseous union by 6 weeks after surgery. No screw loosening or implant-related complications occurred in any patient. There was pelvic canal narrowing in six of nine patients (median reduction in pelvic canal diameter was 4·9%). No intraoperative or postoperative complications were reported. CLINICAL SIGNIFICANCE: Lateral plating of canine and feline ilial fractures with a Synthes TPLO locking compression plate was associated with a low complication rate and satisfactory radiographic and clinical outcomes in this small case series.

A multicentre, clinical evaluation of a hydro-responsive wound dressing: the Glasgow experience.

OBJECTIVE: Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. METHOD: This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. RESULTS: We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within <4 weeks before study inclusion. Of these chronic wounds, 93% demonstrated wound progression upon treatment with HRWD. Despite reported pain levels being low pre- and post-dressing change, overall wound pain improved (reduced) in 48% of patients. Periwound skin condition showed a tendency towards improvement, and the fluid management capabilities of the HRWD was reported as good to excellent in the majority of cases. Wound infections were reduced by at least 60% over the evaluation period. A simple cost-effective analysis demonstrated significant savings using HRWD (£6.33) over current standard practice regimens of a four-step debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). CONCLUSION: HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.

Modeling the benefits and harms of surveillance for hepatocellular carcinoma: Information to support informed choices.

Surveillance by ultrasonography for hepatocellular carcinoma (HCC) for individuals with cirrhosis is recommended. There is debate regarding the effectiveness of surveillance in reducing mortality, and there is little information on the harms available to patients considering surveillance. The aim of this study was to provide estimates of both the benefit and harms of surveillance. A Markov model was built to simulate outcomes of individuals aged 50 years with well-compensated cirrhosis entering surveillance. Following identification of a focal lesion by ultrasound surveillance, further investigations were defined by the European Association for the Study of the Liver/European Organization for Research and Treatment of Cancer recall policy. Benefit and harm outcomes are expressed per 1,000 patients over 5 years. For every 1,000 patients in surveillance over 5 years, there are 13 fewer deaths (95% confidence interval [CI], 12-14) compared with no surveillance, equating to a number needed to screen to prevent one death from HCC of 77. In comparison, many more individuals experienced harm through surveillance. For every 1,000 patients, 150 (95% CI, 146-154) had one or more false-positive tests equating to a number needed to harm from surveillance of 7. As a consequence of a false-positive test, 65 individuals required at least one additional unnecessary computed tomography scan or magnetic resonance imaging and 39 required an unnecessary liver biopsy according to the recall policy. Surveillance benefits were sensitive to the incidence of HCC and the mortality benefit achieved by treatment. Harms were sensitive to the rates of false-positive testing and the frequency of liver biopsy. CONCLUSION: There is a balance between the small absolute mortality benefit to surveillance for HCC and the numerically more frequent harms resulting from false-positive testing. Implementation of the recently revised American Association for the Study of Liver Diseases recommendations is predicted to reduce harms from unnecessary liver biopsy. (Hepatology 2017;66:1546-1555).

Fast and reliable method for As speciation in urine samples containing low levels of As by LC-ICP-MS: Focus on epidemiological studies.

The speciation analysis of As in urine samples can provide important information for epidemiological studies. Considering that these studies involve hundreds or thousands of samples, a fast and reliable method using a simple LC system with short-length mixed bed ion exchange chromatographic column coupled to ICP-MS for As speciation in human urine samples was developed in this work. Separation of AB+TMAO, DMA, AC, MMA and AsIII+AsV was accomplished within 5min with good resolution when ammonium carbonate solutions were used as mobile phases and H2O2 was added to samples to quantitatively convert AsIII-AsV. Repeatability studies yielded RSD values from 2.0% to 4.8% for all species evaluated. Limits of detection (LOD) for As species ranged from 0.003 to 0.051ngg-1. Application of the method to human urine samples from a non-contaminated area showed that the sum of species measured corresponded to 62-125% of the total As in the sample. The recovery values for these species in urine SRM 2669 were in the range of 89-112% and demonstrated the suitability of the proposed method for epidemiological studies.

Social capital strategies to enhance hepatitis C treatment awareness and uptake among men in prison.

Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty-eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse-led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer-based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes.

Antibiotics as part of the management of severe acute malnutrition.

BACKGROUND: Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. The primary outcomes were the rate of nutritional recovery and the mortality rate. RESULTS: A total of 2767 children with severe acute malnutrition were enrolled. In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64). Among children who recovered, the rate of weight gain was increased among those who received antibiotics. No interaction between type of severe acute malnutrition and intervention group was observed for either the rate of nutritional recovery or the mortality rate. CONCLUSIONS: The addition of antibiotics to therapeutic regimens for uncomplicated severe acute malnutrition was associated with a significant improvement in recovery and mortality rates. (Funded by the Hickey Family Foundation and others; ClinicalTrials.gov number, NCT01000298.).

Clinical acceptability of a dressing with matrix technology: a multisite evaluation of acute and chronic wounds.

OBJECTIVE: This article will describe the findings of an evaluation on the performance and clinical acceptability of Urgotul Absorb Border (Urgo Medical), a silicone border adhesive foam dressing containing technology lipidocolloid (TLC) healing matrix technology, as either a primary or secondary dressing in the management of acute and chronic wounds in a multisite evaluation. The purpose of the evaluation was to establish the effectiveness of the silicone border dressing for managing exudate, ease of use, patient comfort and acceptability of the clinician for the dressing to meet with treatment objectives Method: The patient experiences given through verbal or written feedback were also documented. Local Health Board evaluation forms were used to capture data and the authors of this article created a data evaluation tool to collate and subsequently report all study findings. RESULTS: A total of 100 patients with wounds considered suitable for the application of the dressing were selected to take part in the study. In less than a four week period, 38 patients achieved wound healing with a further 36 patients demonstrating wound improvements within the same time period. CONCLUSION: The dressing was found to have met both the clinicians and patients aims when used as either a primary or secondary dressing and was considered suitable for use in both acute and chronic wounds of varying duration.

Presenting data in such a fashion that they can be used by other scientists.

Data always have an experimental uncertainty, i.e. error limits within which the value is very likely to be found. Although the use of statistics is common as is the use of least squares it remains uncommon to see reported the covariance between parameters for an equation to which data have been fitted. This means that a reader cannot properly calculate the error in an extrapolated or interpolated value. Even when the uncertainties in the least squares parameters are reported, errors calculated without the covariance are often too large and almost always different from the correct values calculated using the full formula. This report will demonstrate the importance of covariance in several examples. Systematic errors are also touched on; solubilities of highly hydrophobic and highly insoluble compounds are very difficult to measure for reasons not widely enough appreciated. Aggregation leading to suspended nanodroplets or nanocrystals can lead to spuriously high apparent solubilities. Another class of systematic errors comes from using an equation which is too simple for a desired extrapolation to a value of interest. The magnitude of this possible error is presented for a number of cases. Extrapolation can lead to a value of some use even though it is very uncertain, but expected uncertainty should be pointed out. Recommendations for good publishing practice are proposed for both authors and editors.

Whole-genome sequencing of the Mycobacterium tuberculosis Manila sublineage results in less clustering and better resolution than mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping.

Mycobacterium tuberculosis isolates of the Manila sublineage are genetically homogeneous. In this study, we used whole-genome sequencing (WGS) to type a collection of 36 M. tuberculosis isolates of the Manila family. WGS enabled the subtyping of these 36 isolates into at least 10 distinct clusters. Our results indicate that WGS is a powerful approach to determining the relatedness of Manila family M. tuberculosis isolates.

FreeSolv: a database of experimental and calculated hydration free energies, with input files.

This work provides a curated database of experimental and calculated hydration free energies for small neutral molecules in water, along with molecular structures, input files, references, and annotations. We call this the Free Solvation Database, or FreeSolv. Experimental values were taken from prior literature and will continue to be curated, with updated experimental references and data added as they become available. Calculated values are based on alchemical free energy calculations using molecular dynamics simulations. These used the GAFF small molecule force field in TIP3P water with AM1-BCC charges. Values were calculated with the GROMACS simulation package, with full details given in references cited within the database itself. This database builds in part on a previous, 504-molecule database containing similar information. However, additional curation of both experimental data and calculated values has been done here, and the total number of molecules is now up to 643. Additional information is now included in the database, such as SMILES strings, PubChem compound IDs, accurate reference DOIs, and others. One version of the database is provided in the Supporting Information of this article, but as ongoing updates are envisioned, the database is now versioned and hosted online. In addition to providing the database, this work describes its construction process. The database is available free-of-charge via http://www.escholarship.org/uc/item/6sd403pz .

SAMPL4, a blind challenge for computational solvation free energies: the compounds considered.

For the fifth time I have provided a set of solvation energies (1 M gas to 1 M aqueous) for a SAMPL challenge. In this set there are 23 blind compounds and 30 supplementary compounds of related structure to one of the blind sets, but for which the solvation energy is readily available. The best current values of each compound are presented along with complete documentation of the experimental origins of the solvation energies. The calculations needed to go from reported data to solvation energies are presented, with particular attention to aspects which are new to this set. For some compounds the vapor pressures (VP) were reported for the liquid compound, which is solid at room temperature. To correct from VPsubcooled liquid to VPsublimation requires ΔSfusion, which is only known for mannitol. Estimated values were used for the others, all but one of which were benzene derivatives and expected to have very similar values. The final compound for which ΔSfusion was estimated was menthol, which melts at 42 °C so that modest errors in ΔSfusion will have little effect. It was also necessary to look into the effects of including estimated values of ΔCp on this correction. The approximate sizes of the effects of inclusion of ΔCp in the correction from VPsubcooled liquid to VPsublimation were estimated and it was noted that inclusion of ΔCp invariably makes ΔGS more positive. To extend the set of compounds for which the solvation energy could be calculated we explored the use of boiling point (b.p.) data from Reaxys/Beilstein as a substitute for studies of the VP as a function of temperature. B.p. data are not always reliable so it was necessary to develop a criterion for rejecting outliers. For two compounds (chlorinated guaiacols) it became clear that inclusion represented overreach; for each there were only two independent pressure, temperature points, which is too little for a trustworthy extrapolation. For a number of compounds the extrapolation from lowest temperature at which the VP was reported to 25 °C was long (sometimes over 100°) so that it was necessary to consider whether ΔCp might have significant effects. The problem is that there are no experimental values and possible intramolecular hydrogen bonds make estimation uncertain in some cases. The approximate sizes of the effects of ΔCp were estimated, and it was noted that inclusion of ΔCp in the extrapolation of VP down to room temperature invariably makes ΔGs more negative.

Profiling of rpoB mutations and MICs for rifampin and rifabutin in Mycobacterium tuberculosis.

Resistance to rifampin (RIF) and rifabutin (RFB) in Mycobacterium tuberculosis is associated with mutations within an 81-bp region of the rpoB gene (RIF resistance-determining region [RRDR]). Previous studies have shown that certain mutations in this region are more likely to confer high levels of RIF resistance, while others may be found in phenotypically susceptible isolates. In this study, we sought to determine the relationship between the MICs of RIF and RFB and rpoB RRDR mutations in 32 multidrug-resistant (MDR), 4 RIF-monoresistant, and 5 susceptible M. tuberculosis clinical isolates. The MICs were determined using the MGIT 960 system. Mutations in the rpoB RRDR were determined by Sanger sequencing. RpoB proteins with mutations S531L (a change of S to L at position 531), S531W, H526Y, and H526D and the double mutation D516A-R529Q were associated with high MICs for RIF and RFB. Five isolates carrying the mutations L511P, H526L, H526N, and D516G-S522L were found to be susceptible to RIF. Several mutations were associated with resistance to RIF and susceptibility to RFB (F514FF, D516V, and S522L). Whole-genome sequencing of two MDR isolates without rpoB RRDR mutations revealed a mutation outside the RRDR (V146F; RIF MIC of 50 µg/ml). The implications of the polymorphisms identified in the second of these isolates in RIF resistance need to be further explored. Our study further establishes a correlation between the mutations and the MICs of RIF and, also, RFB in M. tuberculosis. Several rpoB mutations were identified in RIF- and RFB-susceptible isolates. The clinical significance of these findings requires further exploration. Until then, a combination of phenotypic and molecular testing is advisable for drug susceptibility testing.