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Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver-kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality. We retrospectively analyzed all LTA patients at our institution from February 2002 to February 2013 (n = 583) and identified a cohort with severe subacute renal injury (n = 40; creatinine

The Beaty Biodiversity Museum (BBM), at the University of British Columbia, houses over two million biological research specimens, with nearly 40% of the specimen records digitized into databases, unlocking a wealth of information for research and teaching (Table 1). However, these collection databases were neither available nor unified for users. Even museum and collections staff could not digitally access each other’s collections. With a total of 6 collections (in different colors in Fig.1) in 13 separate databases in differing stages of development, across several varying interfaces and systems, our goal was to unify the collection databases through the development of a single search interface (Fig. 1). This was a large collections project with multiple stages of development. Integration of the data was made possible through the efforts of multiple groups to standardize the fields of each database so they conformed to the Darwin Core standard (Group 2009). This mapping of fields allows each of the databases to be displayed and shared in a consistent format. It also simplified the integration of data for popular data aggregators (Canadensys, VertNet, FishNet2, Consortium of Pacific Northwest Herbaria, Electronic Atlas of the Plants of British Columbia, and Global Biodiversity Information Facility). When this first step was achieved, many features such as standarized georeferencing, simplified reporting and unified search interfaces could be implemented to aid all users, e.g., curators, museum staff, researchers, and the public. Through this new interface, it is possible to browse the near entirety of every digitized record within the museum with an in-house solution provided by the Beaty Biodiversity Museum.

Transplant recipients have elevated cancer risk, perhaps partly due to direct carcinogenic effects of immunosuppressive medications. Experimental evidence indicates that calcineurin inhibitors given to transplant recipients increase cellular expression of transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), which could promote cancer. To assess the potential role of these pathways in the transplantation setting, we conducted a case-control study nested in a cohort of liver recipients. Cases had nonmelanoma skin cancer (N = 84), cancer of the lung (N = 29), kidney (N = 20), or colorectum (N = 17), or melanoma (N = 3). We selected N = 463 recipients without cancer as controls. TGF-β1 and VEGF levels were measured in sera obtained, on average, approximately 3 years before case diagnosis/control selection. We also measured platelet factor 4 (PF4), a marker of ex vivo platelet degranulation, because TGF-β1 and VEGF can be released from platelets, and we developed a statistical model to isolate the platelet-derived fraction from the remaining circulating component. Compared with controls, lung cancer cases had higher levels of TGF-β1 (median 22.8 vs. 19.4 ng/mL, P = 0.02) and VEGF (277 vs. 186 pg/mL, P = 0.02). However, lung cancer cases also had higher platelet counts (P = 0.08) and PF4 levels (P = 0.02), while residual serum levels of TGF-β1 and VEGF, after accounting for PF4, were unassociated with lung cancer (P = 0.40 and P = 0.15, respectively). Associations were not seen for other cancers. In conclusion, TGF-β1 and VEGF levels were increased in association with lung cancer among transplant recipients, which may be explained by increased platelet counts and platelet degranulation in lung cancer cases.

Hepatitis C virus (HCV) fibrosis progression after liver transplantation (LT) is accelerated in comparison with fibrosis progression before transplantation. The vast majority of the risk factors for fibrosis progression after LT are not modifiable. With the goal of identifying modifiable risk factors for fibrosis progression, we evaluated the impact of preformed and de novo donor-specific human leukocyte antigen alloantibodies (DSAs) on fibrosis progression after LT in HCV-viremic patients. After blinding, we analyzed all 507 HCV-viremic patients who underwent primary LT from January 2000 to May 2009 and had pretransplant and posttransplant samples available for analysis (86% of the total) for preformed and de novo class I and class II DSAs with a mean fluorescence intensity ≥ 5000 with single-antigen bead technology. Fibrosis was assessed on the basis of indication and protocol liver biopsies; compliance with protocol liver biopsies at 1, 2, and 5 years was ≥80%. Preformed class I DSAs [hazard ratio (HR) = 1.44, P = 0.04] and class II DSAs (HR = 1.86, P

Background & Aims Non-invasive predictors identifying subjects with compensated liver disease at highest risk for transitioning to a decompensated state are lacking. We hypothesized that liver shear stiffness as measured by magnetic resonance elastography is an important non-invasive predictor of hepatic decompensation. Methods Among patients with advanced fibrosis undergoing magnetic resonance elastography (2007–2011), a baseline cohort and follow up cohort (compensated liver disease) were established. Cause specific cox proportional hazards analysis adjusting for competing risks was utilized to determine the association between elevated liver shear stiffness and development of decompensation (hepatic encephalopathy, ascites, variceal bleeding). Results In the baseline cohort (n=430), subjects with decompensated liver disease had a significantly higher mean liver shear stiffness (6.8kPa, IQR 4.9–8.5) as compared to subjects with compensated liver disease (5.2kPa, IQR 4.1–6.8). After adjustment for Model for End Stage Liver Disease score, hepatitis C, age, gender, albumin, and platelet count, the mean liver shear stiffness (OR=1.13, 95% CI 1.03–1.27) was independently associated with decompensated cirrhosis at baseline. Over a median follow up of 27months (n=167), 7.2% of subjects with compensated disease experienced hepatic decompensation. In the follow up cohort, the hazard of hepatic decompensation was 1.42 (95% CI 1.16–1.75) per unit increase in liver shear stiffness over time. The hazard of hepatic decompensation was 4.96 (95% CI 1.4–17.0, p =0.019) for a subject with compensated disease and mean LSS value ⩾5.8kPa as compared to an individual with compensated disease and lower mean LSS values. Conclusion Baseline liver shear stiffness assessed by magnetic resonance elastography is independently associated with decompensated liver disease.

Chronic hepatitis C virus (HCV) is the most common disease indication for liver transplantation (LT). Outcomes are compromised by near universal recurrence of HCV. A prospective multi-center randomized study to evaluate immunosuppressive strategies in HCV+ transplant recipients provided the opportunity to assess impact of live donor (LD) LT. Two hundred and ninety-five patients undergoing LT for HCV (260 deceased donor [DD] recipients/35 LD recipients), randomized to three regimens, were followed for two yr for patient and graft survival and rate and severity of recurrent HCV. Biopsies were performed at baseline, 3, 12, and 24 months. One- and two-yr patient survival for LD recipients was 88.1% and 81.1% vs. 90.5% and 84.6% for DD recipients (p = 0.5665). One- and two-yr graft survival for LD recipients was 82.9% and 76.2% vs. 87.9% and 81.7% for DD recipients (p = 0.3921). Recurrent HCV did not account for more deaths or graft losses in the LD recipients. In this prospective study, controlled for immunosuppression, use of LD organs did not increase the rate or severity of HCV recurrence. The more elective nature of LDLT affords an opportunity to manipulate donor and recipient factors that can impact upon outcomes.

Five different immobilized NAD+ derivatives were employed to compare the behavior of four amino acid dehydrogenases chromatographed using kinetic-based enzyme capture strategies (KBECS): S6-, N6-, N1-, 8′-azo-, and pyrophosphate-linked immobilized NAD+. The amino acid dehydrogenases were NAD+-dependent phenylalanine (EC 1.4.1.20), alanine (EC 1.4.1.1), and leucine (EC 1.4.1.9) dehydrogenases from various microbial species and NAD(P)+-dependent glutamate dehydrogenase from bovine liver (GDH; EC 1.4.1.3). KBECS for bovine heart l -lactate dehydrogenase (EC 1.1.1.27) and yeast alcohol dehydrogenase (EC 1.1.1.1) were also applied to assist in a preliminary assessment of the immobilized cofactor derivatives. Results confirm that the majority of the enzymes studied retained affinity for NAD+ immobilized through an N6 linkage, as opposed to an N1 linkage, replacement of the nitrogen with sulfur to produce an S6 linkage, or attachment of the cofactor through the C8 position or the pyrophosphate group of the cofactor. The one exception to this was the dual-cofactor-specific GDH from bovine liver, which showed no affinity for N6-linked NAD+ but was biospecifically adsorbed to S6-linked NAD+ derivatives in the presence of its soluble KBEC ligand. The molecular basis for this is discussed together with the implications for future development and application of KBECS.

Full of wit, anarchy and humour Fred tops the list of big book adventures! Fred the kitten is terrified of Horrible Harry, but one day he makes a great effort to conquer his fear. By Allison Hedley

This study is concerned with the development of kinetic-based bioaffinity chromatographic systems for purification of ATP-dependent kinases, with a particular focus on the allosteric yeast hexokinase enzyme (EC 2.7.1.1). Synthesis and characterization of highly substituted N(6)-linked and S(6)-linked immobilized ATP derivatives are described using a rapid solid-phase modular approach. Evaluation of the new immobilized ATP derivatives has been carried out using model chromatographic studies with yeast hexokinase, employing specific substrate analogues (N-acetyl-D-glucosamine and suramin) to promote biospecific adsorption, in the presence and absence of citrate (a so-called allosteric activator of hexokinase activity). In this paper, successful bioaffinity chromatography systems were developed for yeast hexokinase and, as a result, interesting binding and catalytic properties of the enzyme were highlighted and explored. The overall results confirm the potential for extrapolation of the kinetic locking-on tactic, a general kinetic-based bioaffinity approach already developed for the NAD(P)(+)-dependent dehydrogenases, to ATP/ADP-dependent enzymes. However, in view of the enhancement of the intrinsic ATPase activity of hexokinase with glucosamine derivatives, and the coincidental hydrolysis of immobilized ATP to immobilized ADP, future developments necessary to support adaptation of the approach to ATP-dependent enzymes are discussed.

Premise of the study: Constructing complete, accurate plant DNA barcode reference libraries can be logistically challenging for large-scale floras. Here we demonstrate the promise and challenges of using herbarium collections for building a DNA barcode reference library for the vascular plant flora of Canada. Methods: Our study examined 20,816 specimens representing 5076 of 5190 vascular plant species in Canada (98%). For 98% of the specimens, at least one of the DNA barcode regions was recovered from the plastid loci rbcL and matK and from the nuclear ITS2 region. We used beta regression to quantify the effects of age, type of preservation, and taxonomic affiliation (family) on DNA sequence recovery. Results: Specimen age and method of preservation had significant effects on sequence recovery for all markers, but influenced some families more (e.g., Boraginaceae) than others (e.g., Asteraceae). Discussion: Our DNA barcode library represents an unparalleled resource for metagenomic and ecological genetic ...

For many species, understanding how climate influences the timing of seasonal life history events (phenology) is limited by the availability of long-term data. Further, long-term studies of plant phenology are often local in scale. Recent efforts to digitize herbarium collections make it possible to examine large numbers of specimens from multiple species over broad geographic regions. In the Pacific Northwest (PNW), understory plant species found in old-growth forests may be buffered against climate warming (Frey et al. 2016). Using 8,500 specimens of 40 plant species housed in 25 herbaria collected over more than 100 years in the PNW we analyzed whether these species have experienced shifts in flowering phenology corresponding to long-term climate warming. Our findings were mixed, with some species experiencing earlier flowering phenology over time while others have not shifted their flowering phenology since the early-1900s. Responses were dependent on life-history, including habitat preference and timing of flowering. These results demonstrate that herbarium collections are an important tool for examining long-term flowering phenological over broad geographic areas and habitat types. Further, flowering phenology does not uniformly shift in correlation with climate warming.

ObjectivesAdequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation.MethodsA retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively

Hepatitis C virus (HCV) fibrosis progression after liver transplantation (LT) is accelerated in comparison with fibrosis progression before transplantation. The vast majority of the risk factors for fibrosis progression after LT are not modifiable. With the goal of identifying modifiable risk factors for fibrosis progression, we evaluated the impact of preformed and de novo donor-specific human leukocyte antigen alloantibodies (DSAs) on fibrosis progression after LT in HCV-viremic patients. After blinding, we analyzed all 507 HCV-viremic patients who underwent primary LT from January 2000 to May 2009 and had pretransplant and posttransplant samples available for analysis (86% of the total) for preformed and de novo class I and class II DSAs with a mean fluorescence intensity ≥ 5000 with single-antigen bead technology. Fibrosis was assessed on the basis of indication and protocol liver biopsies; compliance with protocol liver biopsies at 1, 2, and 5 years was ≥80%. Preformed class I DSAs [hazard ratio (HR) = 1.44, P = 0.04] and class II DSAs (HR = 1.86, P 0.001) were independent predictors of progression to stage 2-4 fibrosis, and de novo DSAs (HR = 1.41, P = 0.07) had borderline significance. In addition, preformed class I DSAs (HR = 1.63, P = 0.03) and class II DSAs (HR = 1.72, P = 0.03) were statistically significantly associated with an increased risk of death. In conclusion, after we controlled for donor and recipient characteristics in multivariate modeling, DSAs were independently associated with fibrosis progression and death after LT in HCV-viremic patients.

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased actuarial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P

We prospectively studied adult liver transplant (OLTX) recipients to evaluate the effect of OLTX on quality of life (QOL). Over an 8-year period, all adult patients undergoing OLTX at our institution were asked to complete a psychological questionnaire that probed broad facets of QOL. Patients seen for their 1, 2, and 5 or more-year post-OLTX visits were also asked to complete the form. Questions were then grouped by categories broadly highlighting self-image (SI), health perception (HP), ability to function (F), and ability to work (W). Questions ranged from demographic and occupational topics to symptom distress/frequency, activities of daily living, and the impact of health on daily life. Numerical scores were assigned to each question, and added to derive scores on SI, HP, and F. Higher scores reflect better QOL. Employment data (W) were also compared, though not amenable to scoring. A total of 573 forms were completed (210 pretransplant, 150 at 1 year, 131 at 2 years, 79 at 5 years). All posttransplant scores were significantly higher than pretransplant ones (P≤.0001, ANOVA). Scores at post-transplant time points were not significantly different from each other. Subscores of SI and HP revealed less symptom frequency and distress following OLTX (P≤.0003) continuing to beyond 5 years. Health limitations on activities decreased both at 1 year post-OLTX and again at 2 years (P≤.0001) and were sustained to beyond 5 years. Fewer people were working for pay at 1 year post-compared with pre-OLTX but pre-OLTX levels of employment had been regained by the second year, continuing to increase to beyond 5 years. OLTX leads to improved QOL by the end of the first post-transplant year, sustained through the 5th posttransplant year and beyond. Self-image, functioning ability, and perception of health status were significantly improved. Ill health interference in daily life continues to decrease as OLTX becomes more remote. Employment suffers early after OLTX but recovers by the second post-OLTX year and continues to increase long-term

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A,B,DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P=0.0051 and P=0.023). Neither B cell-positive cross-match nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA ≤ 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA Analysis of HLA compatibility demonstrated a significant impact on patient's survival, comparing only 0–2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P=0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mismatched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P=0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P=0.04).

Chronic hepatitis C virus (HCV) is the most common disease indication for liver transplantation (LT). Outcomes are compromised by near universal recurrence of HCV. A prospective multi-center randomized study to evaluate immunosuppressive strategies in HCV+ transplant recipients provided the opportunity to assess impact of live donor (LD) LT. Two hundred and ninety-five patients undergoing LT for HCV (260 deceased donor [DD] recipients/35 LD recipients), randomized to three regimens, were followed for two yr for patient and graft survival and rate and severity of recurrent HCV. Biopsies were performed at baseline, 3, 12, and 24 months. One- and two-yr patient survival for LD recipients was 88.1% and 81.1% vs. 90.5% and 84.6% for DD recipients (p = 0.5665). One- and two-yr graft survival for LD recipients was 82.9% and 76.2% vs. 87.9% and 81.7% for DD recipients (p = 0.3921). Recurrent HCV did not account for more deaths or graft losses in the LD recipients. In this prospective study, controlled for immunosuppression, use of LD organs did not increase the rate or severity of HCV recurrence. The more elective nature of LDLT affords an opportunity to manipulate donor and recipient factors that can impact upon outcomes.

Background & Aims Many patients with cryptogenic cirrhosis (CC) have other conditions associated with nonalcoholic steatohepatitis (NASH) that put them at risk for complications that preclude orthotopic liver transplantation (OLT). Methods We followed all patients with NASH and CC who were evaluated for OLT (n = 218) at Baylor Simmons Transplant Institute between March 2002 and May 2008. Data were compared with those from patients evaluated for OLT because of hepatitis C virus (HCV)-associated cirrhosis (n = 646). Results Patients with NASH and CC were older, more likely to be female, had a higher body mass index, and a greater prevalence of diabetes and hypertension, compared with patients with HCV-associated cirrhosis, but the 2 groups had similar model for end-stage liver disease (MELD) scores. NASH and CC in patients with MELD scores ≤15 were less likely to progress; these patients were less likely to receive OLT and more likely to die or be taken off the wait list because they were too sick, compared with patients with HCV-associated cirrhosis. The median progression rate among patients with NASH and CC was 1.3 MELD points per year versus 3.2 MELD points per year for the HCV group (P = .003). Among patients with MELD scores >15, there were no differences among groups in percentage that received transplants or rate of MELD score progression. Hepatocellular carcinoma occurred in 2.7% of patients with NASH and CC per year, compared with 4.7% per year among those with HCV-associated cirrhosis. Conclusions Patients with NASH and CC and low MELD scores have slower disease progression than patients with HCV-associated cirrhosis and are less likely to receive OLT.

The aim of this case series was to retrospectively examine the symptom response of irritable bowel syndrome with constipation (IBS-C) patients administered an herbal extract in a real-world setting. Twenty-four IBS-C patients in a community office practice were provided a combination over-the-counter dietary supplement composed of quebracho (150 mg), conker tree (470 mg) and M. balsamea Willd (0.2 mL) extracts (Atrantil™) and chose to take the formulation for a minimum of 2 wk in an attempt to manage their symptoms. Patient responses to the supplement were assessed by visual analogue scale (VAS) for abdominal pain, constipation and bloating at baseline and at 2 wk as part of standard-of-care. Patient scores from VAS assessments recorded in medical chart data were retrospectively compiled and assessed for the effects of the combined extract on symptoms. Sign tests were used to compare changes from baseline to 2 wk of taking the extract. Significance was defined as P < 0.05. Twenty-one of 24 patients (88%) responded to the dietary supplement as measured by individual improvements in VAS scores for abdominal pain, bloating and constipation symptoms comparing scores prior to administration of the extract against those reported after 2 wk. There were also significant improvements in individual as well as mean VAS scores after 2 wk of administration of the combined extract compared to baseline for abdominal pain [8.0 (6.5, 9.0) vs 2.0 (1.0, 3.0), P < 0.001], bloating [8.0 (7.0, 9.0) vs 1.0 (1.0, 2.0), P < 0.001] and constipation [6.0 (3.0, 8.0) vs 2.0 (1.0, 3.0), P < 0.001], respectively. In addition, 21 of 24 patients expressed improved quality of life while taking the formulation. There were no reported side effects to administration of the dietary supplement in this practice population suggesting excellent tolerance of the formulation. This pilot retrospective analysis of symptom scores from patients before and after consuming a quebracho/conker tree/M. balsamea Willd extract may support the formulation’s use in IBS-C.

To determine the overall efficiency of processes designed to convert lignocellulosic polysaccharides to ethanol, it is first necessary to determine the composition of the lignocellulosic substrates. Three standard methods routinely referenced in the literature for this purpose are monoethanolamine, trifluoroacetic acid and concentrated sulphuric acid-based methods. However, in the course of our studies, the suitability of these standard methods for analysis of wastepaper and wheat straw came into question. This paper details our investigations in this area, together with recommendations for appropriate modifications to one of the standard methods for reproducible and representative lignocellulosic compositional analysis of waste paper and cereal straw.

The driving abilities of adults appear to diminish in conjunction with age-related physical and cognitive changes. In this exploratory study, rehabilitation strategies used with 21 older adults were examined to determine the most effective method of retraining driving skills. Subjects, who met the study's eligibility criteria (aged 55 years or older, held a valid driver's license, drove a minimum of 1000 miles/year, and no participation in an adult re-education program) received driver simulation training, classroom viewing of driver simulation films, or no treatment. Outcome measures included on-road and clinical evaluations, as well as self-report information. A significant difference was found between treatment type and subjects' accuracy scores for on-road evaluation, thus suggesting that driving simulation may result in a significant improvement in older adults' driving performance as compared to other intervention strategies. The study has particular relevance to occupational therapy practitioners, with their growing involvement in driving programs throughout the United States.