Predictive learning, prediction errors, and attention: evidence from event-related potentials and eye tracking.

Prediction error ("surprise") affects the rate of learning: We learn more rapidly about cues for which we initially make incorrect predictions than cues for which our initial predictions are correct. The current studies employ electrophysiological measures to reveal early attentional differentiation of events that differ in their previous involvement in errors of predictive judgment. Error-related events attract more attention, as evidenced by features of event-related scalp potentials previously implicated in selective visual attention (selection negativity, augmented anterior N1). The earliest differences detected occurred around 120 msec after stimulus onset, and distributed source localization (LORETA) indicated that the inferior temporal regions were one source of the earliest differences. In addition, stimuli associated with the production of prediction errors show higher dwell times in an eye-tracking procedure. Our data support the view that early attentional processes play a role in human associative learning.

Improvement in screening performance and diagnosis of congenital hypothyroidism in Scotland 1979-2003.

AIM: To assess the Scottish newborn screening programme for congenital hypothyroidism from 1994 to 2003 (period 2) for performance and compare with an initial audit covering 1979 to 1993 (period 1). DESIGN: Performance data-age at blood spot sampling, notification by screening laboratory, start of treatment, and the prevalence of late testing, notification or treatment-were compared, together with the incidence of congenital hypothyroidism. RESULTS: Comparing data for period 2 with period 1, the mean annual incidence of true congenital hypothyroidism was 1:3655 live births v 1:4363. Median age for Guthrie sampling (all referrals) was 6 v 7 days (p<0.0001). Late sampling (>10 days) had fallen from 10.7% to 7%. For infants requiring repeat sampling before notification, the median (range) interval between initial and final repeat samples was 11 (1 to 52) compared with 14 (3 to 73) days. Median age at notification for true congenital hypothyroidism was 10 v 12 days (p <0.0001). Late notification (>15 days) was justifiable (mild TSH elevation) in 10 of 13 patients in period 2. Median age at start of treatment for true congenital hypothyroidism had improved to 11 days from 13.5 days. For true congenital hypothyroidism, late treatment (>16 days) occurred in 7% of patients compared with 19% (p<0.0001). CONCLUSIONS: There has been an improvement in performance measures for the congenital hypothyroidism screening programme in Scotland. However, late sampling, occurring primarily in inpatients and which is never justified, remains a problem, while the interval between initial and recall sampling is a further source of delay.

Needs of parents of the child hospitalised with acquired brain damage.

This paper describes the findings of a descriptive study into needs of parents of children with Acquired Brain Damage during hospitalisation. Thirty four parents of 28 children treated at a tertiary referral pediatric hospital were interviewed. Parents described their experiences during their child's hospitalisation and identified needs which, when met, enabled them to care for their children and cope with the sudden illness and disabilities. Three themes were identified: services that optimised the child's recovery, services which supported parents cope with child's illness and services assisting in maintenance of family functioning and stability. An emerging model of parental needs and nursing interventions to meet these are identified.

Molecular basis for p38 protein kinase inhibitor specificity.

p38 is a member of the mitogen-activated protein (MAP) kinase family and is a critical enzyme in the proinflammatory cytokine pathway. Other MAP kinase group members that share both structural and functional homology to p38 include the c-Jun NH2-terminal kinases (JNKs or SAPKs) and the extracellular-regulated protein kinases (ERKs). In this study, we determined the molecular basis for p38alpha inhibitor specificity exhibited by five compounds in the diarylimidazole, triarylimidazole, and triarylpyrrole classes of protein kinase inhibitors. These compounds are significantly more potent inhibitors of p38 compared to the JNKs and ERKs. Three active site ATP-binding domain residues in p38, T106, M109, and A157, selected based on primary sequence alignment, molecular modeling, and X-ray crystal structure data, were mutated to assess their role in inhibitor binding and enzymatic catalysis. All mutants, with the exception of T106M, had kinase activity within 3-fold of wild-type p38. Mutation of T106 to glutamine, the residue present at the corresponding position in ERK-2, or methionine, the corresponding residue in p38gamma, p38delta, and the JNKs, rendered all five inhibitors ineffective. The diarylimidazoles had approximately a 6-fold decrease in potency toward M109A p38. For the mutant A157V, all diarylimidazoles and triarylimidazoles tested were 5-10-fold more potent compared with wild-type p38. In contrast, two triarylpyrroles were 15-40-fold less potent versus A157V p38. These results showed that the molecular basis for the specificity of the p38 inhibitors was attributed largely to threonine 106 in p38 and that methionine 109 contributes to increased binding affinity for imidazole based inhibitors.

A cooperative MLT program between a community college and a university.

In 1991 the University of Utah collaborated with Salt Lake Community College to establish a jointly sponsored Medical Laboratory Technician (MLT) program. With documented need for MLTs in Utah and surrounding states, both institutions combined their resources to create an associate degree program that neither institution could offer alone. The first academic year of prerequisite science and liberal education courses are completed at the Community College followed by a second year of professional didactic and laboratory courses taught by faculty of the Medical Technology (MT) Program at the University of Utah, Department of Pathology. Following the second year of professional courses, MLT students complete 15 weeks of clinical rotations in the Salt Lake Metropolitan area. MLT students as well as MT students benefit from their shared experiences in combined courses that are taught on the university campus.

Pyrroles and other heterocycles as inhibitors of p38 kinase.

Investigation of furans, pyrroles and pyrazolones identified 3-pyridyl-2,5-diaryl-pyrroles as potent, orally bioavailable inhibitors of p38 kinase. 3-(4-pyridyl-2-(4-fluoro-phenyl)-5-(4-methylsulfinylphenyl)-pyrrol e (L-167307) reduces secondary paw swelling in the rat adjuvant arthritis model: ID50 = 7.4 mg/kg/b.i.d.

Imaging of prostatic and testicular disorders.

Ultrasound is playing an increasingly important role in the evaluation of testicular and prostatic abnormalities. It provides differentiation of intratesticular lesions, which are most likely malignant, from extratesticular lesions, which are usually benign. Duplex sonography enables accurate rapid diagnosis of testicular torsion and distinction between this and epididymo-orchitis. Ultrasound can also be used to evaluate the traumatised testis. Ultrasound has some advantages over IVP for assessment of the renal tracts and prostate in patients with prostatism. The development of transrectal ultrasound enables better evaluation of the prostate gland than has been previously possible and enables ultrasound-guided transrectal biopsies of prostatic lesions to detect early prostatic carcinoma. TRUS is likely to play an increasing role in evaluation of the prostate as it becomes more readily available. Other imaging modalities have a role in specific circumstances as outlined.

The perivertebral collar--a new sign in lymphoproliferative malignancies.

Nine patients with lymphoproliferative malignancies, one of whom had not been previously diagnosed, were found on CT examination for back pain to have partial or complete soft tissue perivertebral collars. The thoracic and or lumbar regions were involved in all. Only 3 had gross bony changes at the time, and in others the changes appeared so innocuous that in combination with the vague clinical symptoms their significance was underestimated. Five patients ultimately had episodes of cord compression, and in all nine the appearance of this spinal lesion appeared to be of grave prognostic significance. All 9 were dead within 1 year of the presentation of their spinal lesions. The observation of a perivertebral collar in the context of a known or suspected lymphoproliferative malignancy should therefore raise the strong suspicion of spinal involvement. The vertebrae should be examined on bone windows and the contents of the spinal canal on narrow windows to assess bony and epidural spread.

Sonographic appearance of plasmacytoma of the testis.

A case of solitary extramedullary plasmacytoma of the testis is presented demonstrating the appearances on ultrasound. The clinical implications of this diagnosis are discussed.

Suitability of new chlamydia transport medium for transport of herpes simplex virus.

A new chlamydia transport medium (ChlamydiaPort; Scott Laboratories, Inc., Fiskeville, R.I.) was evaluated for its suitability as a transport medium for herpes simplex virus (HSV). Two laboratory HSV strains (McIntyre and 333) and two clinical isolates (AO218 and AO301) were suspended in ChlamydiaPort, ViraPort (Scott Laboratories), and cell culture medium and maintained at 2 and 22 degrees C. Samples were tested at various time intervals to determine surviving virus. The range of half-lives of the HSV strains held at 2 degrees C in ChlamydiaPort medium was from 3.5 to 10 days, while virus stability was greater in ViraPort and less in cell culture medium. These HSV strains held at 22 degrees C in ChlamydiaPort had half-lives from 1.5 to 6 days, which were significantly greater than the half-lives of the viruses held in either tissue culture medium or ViraPort. Clinical specimens were tested for virus by using the Selecticult-HSV (Scott Laboratories) system to determine the performance of the transport medium under field conditions. Clinical specimens maintained up to 5 days at ambient temperatures in ChlamydiaPort medium appeared suitable for diagnostic testing without detectable loss of positive specimens. In addition, there was a significant decrease in the average time required for diagnosis when compared with a standard transport system, Virocult (Microdiagnostics, Cleveland, Ohio). These results show that HSV infections can be successfully diagnosed in distant virology laboratories by shipping specimens in ChlamydiaPort transport medium at ambient temperatures.

Production and reactivity of immune sera specific for HADEN virus polypeptide antigens.

Antisera were prepared against the three structural polypeptides of HADEN virus dissociated with sodium dodecyl sulfate. These immunological reagents were used in immunofluorescence tests to study the kinetics and location of polypeptide antigen appearance in infected cells. These sera did not neutralize virus infectivity, did not cross-react with adenovirus-associated virus-infected cells, and reacted in complement fixation tests with sodium dodecyl sulfate-dissociated virus, but not with complete virus antigen. The polypeptide antigens were heat labile, and all appeared in infected cells at least 2 h prior to whole-virus antigen.