Brian Davidson

Perceptual flexibility in word recognition: strategies affect orthographic computation but not lexical access.

Four tachistoscopic forced-choice recognition experiments explored the flexibility of processes underlying word perception. Stimuli were words, orthographically regular but unfamiliar pseudowords, and orthographically irregular nonsense strings. In the first two experiments, subjects knew that several different kinds of stimuli would occur in each block of trials and that one kind would occur much more often than the others. No matter which stimulus subjects expected to see most often, accuracy on words and pseudowords differed little, and both were identified considerably better than nonsense. In the third and fourth experiments, subjects were led to believe that only on stimulus type would occur but were surreptitiously shown another type on a small number of trials. Words were again identified more accurately than nonsense, and the size of the effect was independent of expectations. However, when either words or nonsense strings were expected exclusively, pseudoword accuracy did not differ from nonsense accuracy. Only when subjects knew that pseudowords would occur did they identify pseudowords more accurately than nonsense. This dissociation between word and pseudoword identification indicates the operation of two independent encoding mechanisms during tachistoscopic recognition, a stimulus-specific or logogenlike system sensitive to particular familiar strings and an orthographic mechanism sensitive to generally applicable constraints on letter sequencing. The stimulus-specific mechanism appears to be utilized automatically, but use of the orthographic mechanism is under strategic control. As shown in the first two experiments, however, rather extraordinary measures were required to demonstrate the flexibility of the orthographic processes used in this task.

Dyslexic and Normal Readers' Eye Movements

: Dyslexic and normal readers eye movements were compared while tracking a moving fixation point and in reading. Contrary to previous reports, the dyslexic and normal readers did not differ in their number of saccades, percentage of regressions, or stability of fixations in the tracking task. Thus, defective oculomotor control was not associated with or a causal factor in dyslexia, and the dyslexics abnormal eye movements in reading must be related to differences in higher cognitive processes. However, individual differences in oculmotor efficiency, independent of reading ability, were found within both the dyslexic and normal groups, and these differences were correlated in reading and tracking tasks.

Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation.

Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5u2009×u20095u2009×u20095u2009mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.

The role of different immunosuppression in the long-term histological outcome of HCV reinfection after liver transplantation for HCV cirrhosis

Background. The effect of the type of immunosuppression on the course of posttransplant hepatitis C virus (HCV) infection is unclear. The aim of this study was to evaluate the histological outcome of posttransplant HCV infection with respect to initial immunosuppressive therapy in a cohort of 59 of 65 HCV positive transplant patients who survived at least 12 months. Methods. Initial immunosuppressive therapy was triple (cyclosporine or tacrolimus and azathioprine and prednisolone) in 41, double (cyclosporine and prednisolone) in 5, and single (cyclosporine or tacrolimus) in 13 patients. There was blinded histological evaluation, based on necroinflammatory activity (grading score:0–18) and fibrosis (staging score:0–6). The median histological follow-up was 36 (12–72) months. Results. In the last liver biopsy, high necroinflammatory activity indicating chronic hepatitis (grading score ≥4) was found in 42 (71%) and severe fibrosis or cirrhosis (staging score ≥4) in 18 (30.5%) patients. High necroinflammatory activity was associated significantly with absence of pretransplant alcohol abuse (P =0.01) and relatively with occurrence of posttransplant acute lobular hepatitis C (P =0.055). Development of severe fibrosis or cirrhosis was significantly associated only with the type of initial immunosuppressive therapy. In particular, severe fibrosis or cirrhosis developed significantly more frequently in patients treated with triple or double (17/46 or 37%) than with single initial immunosuppressive therapy (1/13 or 7.7%) (adjusted for biopsy time:P =0.045). Conclusions. Severe fibrosis or cirrhosis appears to develop in 30% of HCV transplant patients in a median of 3 years and to be associated with heavier initial immunosuppression.

Biliary anastomosis after liver transplantation does not benefit from T tube splintage.

T tubes are commonly used to splint biliary anastomoses after liver transplantation. Although several advantages are claimed for this approach, there is undoubtedly some iatrogenic morbidity associated with the use of T tubes in this situation. We have evaluated 120 consecutive biliary reconstructions after liver transplant, the majority of which were unsplinted end to end bile duct anastomoses. We have shown that biliary leakage and stricture rates are not significantly affected by T tubes. We have also shown that endoscopic retrograde cholangiopancreatography and percutaneous cholangiography are reliable posttransplant methods for cholangiography and stricture dilatation. Routine T tube splintage of post-liver transplant biliary anastomoses is unjustified.

Development of phonetic memory in disabled and normal readers

The development of phonetic codes in memory of 141 pairs of normal and disabled readers from 7.8 to 16.8 years of age was tested with a task adapted from L. S. Mark, D. Shankweiler, I. Y. Liberman, and C. A. Fowler (Memory & Cognition, 1977, 5, 623-629) that measured false-positive errors in recognition memory for foil words which rhymed with words in the memory list versus foil words that did not rhyme. Our younger subjects replicated Mark et al., showing a larger difference between rhyming and nonrhyming false-positive errors for the normal readers. The older disabled readers phonetic effect was comparable to that of the younger normal readers, suggesting a developmental lag in their use of phonetic coding in memory. Surprisingly, the normal readers phonetic effect declined with age in the recognition task, but they maintained a significant advantage across age in the auditory WISC-R digit span recall test, and a test of phonological nonword decoding. The normals decline with age in rhyming confusion may be due to an increase in the precision of their phonetic codes.

Mycophenolate Mofetil Monotherapy In Stable Liver Transplant Patients With Cyclosporine-induced Renal Impairment: A Preliminary Report

BACKGROUNDnCyclosporine is the most common maintenance immunosuppressant in liver transplants patients, but it is often associated with nephrotoxicity.nnnMETHODSnWe evaluated the safety and efficacy of monotherapy with mycophenolate mofetil (1 g twice daily) in five stable liver transplant patients with cyclosporine-induced renal impairment despite reduction of cyclosporine to subtherapeutic levels. Follow-up was 8.4+/-2.4 (range: 6-12) months.nnnRESULTSnNo major side effects have been observed to date. Serum creatinine levels were significantly reduced from a median of 201 micromol/L before to 142 micromol/L at 3 months after mycophenolate (P=0.04) and remained low at 6 months. New onset cellular rejection occurred in only one patient after 3 months on mycophenolate monotherapy, and it responded completely to an intravenous course of methylprednisolone.nnnCONCLUSIONSnMonotherapy with mycophenolate mofetil in a dose of 1 g twice daily seems to significantly improve cyclosporine-induced renal impairment in stable liver transplant patients without major side effects or significant risk of rejection.

Regression analyses as a tool for studying reading processes: Comment on Just and Carpenters eye fixation theory

Just and Carpenter (1980) presented a theory of reading based on eye fixations wherein their “psycholinguistic” variables accounted for 72% of the variance in word gaze durations. This comment raises some statistical and theoretical problems with their use of simultaneous regression analysis of gaze duration measures and with the resulting theory of reading. A major problem was the confounding of perceptual with psycholinguistic factors. New eye fixation data are presented to support these criticisms. Analysis of fixations within words revealed that most gaze duration variance was contributed by number of fixations rather than by fixation duration.

The influence of cytomegalovirus viraemia on the outcome of recurrent hepatitis C after liver transplantation.

Background. Several interrelated host and hepatitis C virus (HCV) associated factors have been proposed to explain the variable outcomes in HCV recurrence. Recent evidence suggests that cytomegalovirus (CMV) infection not only is co-factor in progression of HCV recurrence but may precipitate allograft rejection. We investigated whether short-term CMV viremia influences HCV recurrence, the number and grade of acute rejection episodes, and the histological course of HCV recurrence during the first year after orthotopic liver transplantation (OLT) for HCV-related cirrhosis. Methods A cohort of 39 patients transplanted for cirrhosis HCV-related was analyzed. Patients were evaluated twice weekly for CMV infection by a blood polymerase chain reaction (PCR) assay. Triple therapy with cyclosporine or tacrolimus, azathioprine and prednisolone was the initial immunosuppressive regimen. Preemptive treatment with ganciclovir was started when two consecutive PCRs for CMV were positive. Liver biopsies were performed on day 7 after OLT or when indicated. A 3-day IV 1 g methilprednisolone was given to patients with moderate or severe rejection. Ishak’s score was used to grade inflammation and to stage fibrosis. Results Neither CMV viremia nor CMV disease after OLT for HCV-related cirrhosis adversely influenced the incidence and grade of acute rejection episodes nor the histological outcome of post transplant HCV recurrence, during the first year after liver transplantation. Conclusion CMV viremia as detected by PCR does not affect the progression of HCV recurrence in liver grafts.

Cost‐effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost‐effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost‐effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta‐analysis to calculate the diagnostic accuracy of various NITs using a bivariate random‐effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality‐adjusted life‐years; QALYs) using data from the meta‐analysis, literature, and national UK data. We compared the cost‐effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost‐effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more‐potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost‐effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost‐effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1‐4, the incremental treatment cost threshold for the “treat all” strategy to remain the most cost‐effective strategy would be £37,500. Above this threshold, the most cost‐effective option would be noninvasive testing with magnetic resonance elastography (ICERu2009=u2009£9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost‐effective strategy with currently available drugs in developed countries. (Hepatology 2014;60:832–843)