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Objective(s): There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature., Methods: A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage., Results: Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03)., Conclusions: Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort., Level of Evidence: 3 Laryngoscope, 133:1110-1121, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The impact of coronary artery disease (CAD) on outcomes after transcatheter aortic valve replacement (TAVR) is understudied. Literature on the prognostic role of CAD in the survival of patients undergoing TAVR shows conflicting results. This meta-analysis aims to investigate how CAD impacts patient survival following TAVR., Methods and Results: We completed a comprehensive literature search of Embase, MEDLINE, and the Cochrane Library, and included studies reporting outcome of TAVR based on CAD status of patients for the analysis. From the initial 1631 citations, 15 studies reporting on 8013 patients were analyzed using a random-effects model. Of the 8013 patients undergoing TAVR, with a median age of 81.3 years (79-85.1 years), 46.6% (40-55.7) were men and 3899 (48.7%) had CAD (ranging from 30.8% to 78.2% in various studies). Overall, 3121 SAPIEN/SAPIEN XT/SAPIEN 3 (39.6%) and 4763 CoreValve (60.4%) prostheses were implanted, with transfemoral access being the most frequently used approach for the implantation (76.1%). Our analysis showed no significant difference between patients with and without CAD for all-cause mortality at 30 days post TAVR, with a cumulative odds ratio of 1.07 (95% confidence interval, 0.82-1.40; P= 0.62). However, there was a significant increase in all-cause mortality at 1 year in the CAD group compared with patients without CAD, with a cumulative odds ratio of 1.21 (95% confidence interval, 1.07-1.36; P =0.002)., Conclusions: Even though coexisting CAD does not impact 30-day mortality, it does have an impact on 1-year mortality in patients undergoing TAVR. Our results highlight a need to revisit the revascularization strategies for concomitant CAD in patients with TAVR., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Reversibility of left ventricular (LV) dysfunction in high-risk aortic stenosis patient and its impact on survival after transcatheter aortic valve replacement (TAVR) are unclear. We aimed to evaluate longitudinal changes of LV structure and function after TAVR and their impact on survival., Methods and Results: We studied 209 patients with aortic stenosis who underwent TAVR from May 2006 to December 2012. Echocardiograms were used to calculate LV end-diastolic volume index (LVEDVi), LV ejection fraction, LV mass index (LVMi), and global longitudinal strain before, immediately (<10 days), late (1-3 months), and yearly after TAVR. During a median follow-up of 1345 days, 118 patients died, with 26 dying within 1 year. Global longitudinal strain, LVEDVi, LV ejection fraction, and LVMi improved during follow-up. In patients who died during the first year, death was preceded by LVEDVi and LVMi increase. Multivariable longitudinal data analysis showed that aortic regurgitation at baseline, aortic regurgitation at 30 days, and initial LVEDVi were independent predictors of subsequent LVEDVi. In a joint analysis of longitudinal and survival data, baseline Society of Thoracic Surgeons score was predictive of survival, with no additive effect of longitudinal changes in LVEDVi, LVMi, global longitudinal strain, or LV ejection fraction. Presence of aortic regurgitation at 1 month after TAVR was the only predictor of 1-year survival., Conclusions: LV reverse remodeling was observed after TAVR, whereas lack of LVEDVi and LVMi improvement was observed in patients who died during the first year after TAVR. Post-TAVR, aortic regurgitation blocks reverse remodeling and is associated with poor 1-year survival after TAVR., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Four pigeons performed a simultaneous matching-to-sample (MTS) task involving two samples and two comparisons that differed in their pixel density and luminance. After a long history of reinforcers for correct responses after both samples, 15 conditions arranged either continuous reinforcement of correct responses after Sample 1 and extinction for all responses after Sample 2, or vice versa. The sample after which correct responses were reinforced alternated across successive conditions. The disparity between the samples and the disparity between the comparisons were varied independently across conditions in a quasifactorial design. Contrary to predictions of extant quantitative models, which assume that MTS tasks involve two 3-term contingencies of reinforcement, matching accuracies were not at chance levels in these conditions, comparison-selection ratios differed after the two samples, and effects on matching accuracies of both sample disparity and comparison disparity were observed. These results were, however, consistent with ordinal and sometimes quantitative predictions of Jones' (2003) theory of stimulus and reinforcement effects in MTS tasks. This theory asserts that MTS tasks involve four-term contingencies of reinforcement and that any tendency to select one comparison more often than the other over a set of trials reflects meaningful differences between comparison-discrimination accuracies after the two samples., (© Society for the Experimental Analysis of Behavior.)

Response membership in pigeons' stimulus-class formation was evaluated using associative symmetry and class expansion tests. In Experiment 1, pigeons learned hue-hue (AA) and form-form (BB) successive matching plus a modified hue-form (AB) task in which reinforcement was contingent upon a left versus right side-key response after the positive AB sequences. On subsequent BA (symmetry) probe trials, pigeons responded more often to the comparisons on the reverse of the positive than negative AB sequences and, more importantly, preferentially pecked the side key consistent with symmetry after the reversed positive sequences. In Experiment 2, the original three baseline tasks were supplemented by dot-white (CC) successive matching in which reinforcement was contingent upon a left versus right side-key response after the positive CC sequences. Class expansion was then tested by presenting nonreinforced CA and CB successive matching probes. Comparison response rates were mostly nondifferential on CA probes but were uniformly higher on CB probes that consisted of the C samples and B comparisons from the same, hypothesized class. Together, these results provide evidence that responses can become members of stimulus classes, as predicted by Urcuioli's (2008) theory of pigeons' stimulus-class formation and Sidman's (2000) theory of equivalence., (© Society for the Experimental Analysis of Behavior.)

Six pigeons were trained in a delayed matching-to-sample task involving bright- and dim-yellow samples on a central key, a five-peck response requirement to either sample, a constant 1.5-s delay, and the presentation of comparison stimuli composed of red on the left key and green on the right key or vice versa. Green-key responses were occasionally reinforced following the dimmer-yellow sample, and red-key responses were occasionally reinforced following the brighter-yellow sample. Reinforcer delivery was controlled such that the distribution of reinforcers across both comparison-stimulus color and comparison-stimulus location could be varied systematically and independently across conditions. Matching accuracy was high throughout. The ratio of left to right side-key responses increased as the ratio of left to right reinforcers increased, the ratio of red to green responses increased as the ratio of red to green reinforcers increased, and there was no interaction between these variables. However, side-key biases were more sensitive to the distribution of reinforcers across key location than were comparison-color biases to the distribution of reinforcers across key color. An extension of Davison and Tustin's (1978) model of DMTS performance fit the data well, but the results were also consistent with an alternative theory of conditional discrimination performance (Jones, 2003) that calls for a conceptually distinct quantitative model.

Facial bipartition is amongst the most radical craniofacial surgery undertaken but is performed rarely. There is little published information on its anaesthetic management. We undertook a retrospective case-note review of 22 consecutive patients undergoing bipartition surgery by the same surgical team in one centre in the period 1993-2001. There were incomplete data for two cases and these were therefore excluded. Patients were aged 2 months to 19 years. Conditions treated were facial cleft (n = 5), frontonasal dysplasia (n = 7) and facial dysostosis (n = 8).Intra-operative complications included major haemorrhage (n = 4), bradycardia (n = 3) and unintentional tracheal extubation (n = 1). There were no peri-operative deaths. All patients required intra-operative blood transfusion and 15% of them had a postoperative haemoglobin concentration > 115% of their pre-operative value. In this series, four patients required postoperative lung ventilation for a median duration of 3 days. Infants < 14 months old were significantly more likely to receive a massive blood transfusion (p = 0.0002), to have an excessively high postoperative haematocrit (p = 0.008) and to require postoperative lung ventilation (p = 0.0002) compared with older patients. We conclude that patients in this age group have a significantly increased risk of postoperative complications.

Six pigeons performed a simultaneous matching-to-sample (MTS) task involving patterns of dots on a liquid-crystal display. Two samples and two comparisons differed in terms of the density of pixels visible through pecking keys mounted in front of the display. Selections of Comparison 1 after Sample 1, and of Comparison 2 after Sample 2, produced intermittent access to food, and errors always produced a time-out. The disparity between the samples and between the comparisons varied across sets of conditions. The ratio of food deliveries for the two correct responses varied over a wide range within each set of conditions, and one condition arranged extinction for correct responses following Sample 1. The quantitative models proposed by Davison and Tustin (1978), Alsop (1991), and Davison (1991) failed to predict performance in some extreme reinforcer-ratio conditions because comparison choice approached indifference (and strong position biases emerged) when the sample clearly signaled a low (or zero) rate of reinforcement. An alternative conceptualization of the reinforcement contingencies operating in MTS tasks is advanced and was supported by further analyses of the data. This model relates the differential responding between the comparisons following each sample to the differential reinforcement for correct responses following that sample.

Five pigeons were trained on a concurrent-schedule analogue of the "some patches are empty" procedure. Two concurrently available alternatives were arranged on a single response key and were signaled by red and green keylights. A subject could travel between these alternatives by responding on a second yellow "switching" key. Following a changeover to a patch, there was a probability (p) that a single reinforcer would be available on that alternative for a response after a time determined by the value of lambda, a probability of reinforcement per second. The overall scheduling of reinforcers on the two alternatives was arranged nonindependently, and the available alternative was switched after each reinforcer. In Part 1 of the experiment, the probabilities of reinforcement, rho(red) and rho(green), were equal on the two alternatives, and the arranged arrival rates of reinforcers, lambda(red) and lambda(green), were varied across conditions. In Part 2, the reinforcer arrival times were arranged to be equal, and the reinforcer probabilities were varied across conditions. In Part 3, both parameters were varied. The results replicated those seen in studies that have investigated time allocation in a single patch: Both response and time allocation to an alternative increased with decreasing values of lambda and with increasing values of rho, and residence times were consistently greater than those that would maximize obtained reinforcer rates. Furthermore, both response- and time-allocation ratios undermatched mean reinforcer-arrival time and reinforcer-frequency ratios.

Six homing pigeons were trained on a variety of concurrent variable-interval schedules in a switching-key procedure. Unlike previous work, reinforcer ratios of up to 160 to 1 and concurrent extinction variable-interval schedules were arranged in order to investigate choice when reinforcer-frequency outcomes were extremely different. The data obtained over 11 conditions were initially analyzed according to the generalized matching law, which fitted the data well. The generalized matching law was then fitted only to conditions in which the reinforcer ratios were between 1 to 10 and 10 to 1. The deviations of choice measures from the other four more extreme reinforcer-ratio conditions were significantly more towards equal choice than predicted by this second generalized matching fit. A contingency-discriminability model, which predicts such deviations, described the data more effectively than did the generalized matching law, and also correctly predicted the maintenance of responding on both alternatives when one was associated with extinction.

The differential-outcomes effect is manifest as more accurate performance of a delayed conditional discrimination when alternative choice responses are followed by different reinforcers than when they are followed by the same reinforcer. In Experiment 1, a differential-outcomes effect was demonstrated within sessions by signaling the duration of food access for correct responses with stimuli appearing in conjunction with the sample stimuli. The delayed matching-to-sample performance of 5 pigeons was more accurate when green choice responses (matching a green sample) were followed by 3.5-s food access and red choice responses (matching a red sample) were followed by 0.5-s food access (different-outcome trials) than when the correct choice responses were both followed by 1.5-s reinforcers (same-outcome trials). In Experiment 2, the acquisition of this differential-outcomes effect was characterized by a progressive decrease in rate of forgetting on different-outcome trials and no change in rate of forgetting on same-outcome trials. In addition, accuracy at the shortest delay intervals for both different-outcome and same-outcome trials increased over acquisition, but to a greater extent for different-outcome trials. These data suggest that both memorial and attentional (time-dependent and time-independent) factors contribute to the differential-outcomes effect.

Five pigeons were trained in a delayed matching-to-sample task with red and green stimuli. The retention interval between sample-stimulus presentation and the availability of the choice stimuli was varied between 0.01 s and 12 s within each session. The probability of food produced by correct-red and correct-green responses was varied across conditions. Sample-stimulus discriminability and response bias were measured at four different retention intervals. The results of these analyses showed an interaction between the discriminability of the sample stimuli and the control exerted by differential reinforcement. At longer retention intervals, sample discriminability decreased and sensitivity of choice behavior to changes in the red/green reinforcer ratio increased. An analogous relation has been reported in conditional discriminations in which the physical disparity of stimuli has been varied. This correspondence suggests that increasing the delay between presentation of one of two stimuli and an opportunity to respond discriminatively to it may be functionally similar to increasing the physical similarity of the two stimuli.

We describe a patient with growth failure and multiple congenital anomalies characteristic of Fanconi anaemia, but without the classical feature of progressive bone marrow hypoplasia. Following treatment with growth hormone for a period of 8 years, he presented with myelodysplastic syndrome and a karyotypically abnormal clone in the bone marrow (47,XY,+8). The diagnosis of Fanconi anaemia was supported by the induction of abnormally high levels of characteristic chromosome aberrations in peripheral lymphocytes following exposure in vitro to the bifunctional alkylating agent mitomycin C. Immune function studies also identified a selective IgA deficiency. The relative importance of interacting constitutional and exogenous factors involved in the development of preleukaemia in this patient is discussed.

The relationship between oral contraceptives and ethanol metabolism in women was examined in a group of 40 female social drinkers between the ages of 21 and 30. Twenty women taking oral contraceptives and 20 women not taking oral contraceptives were given a moderate dose of ethanol (0.52 g/kg) during the menstrual, intermenstrual and premenstrual phases of the menstrual cycle. The group of women taking oral contraceptives demonstrated a significantly decreased ethanol elimination rate (105 mg/kg/hr) than the women not taking oral contraceptives (121 mg/kg/hr, p less than .005). Ethanol disappearance rate also was significantly decreased for women taking oral contraceptives (0.015%/hr) than women not taking them (0.019%/hr, p less than .001). These results were consistent across the three phases of the menstrual cycle and when body leanness was taken into consideration. The decreased rate of ethanol metabolism in women taking oral contraceptives is consistent with reports of other drugs having decreased metabolic rates in women taking birth control pills. These results suggest that women taking oral contraceptives should be cautioned concerning their possible interaction with ethanol, as well as other drugs.

Ethanol metabolism rates were investigated in a group of 17 male American Indians and a group of 17 male whites of similar age, education, weight, and drinking history. A moderate dose of alcohol (0.52 g/kg) was administered orally to each subject, and blood alcohol levels were determined by breath analysis. The American Indian group demonstrated a significantly faster rate of alcohol metabolism than the white group. The peak blood alcohol level was significantly higher for the American Indians than for the whites, and the American Indian group demonstrated a significantly faster absorption rate than the white group.

Sequential lysis of human bone marrow cells with a monoclonal antibody directed against myeloid cells (TG1) and a rabbit antiserum raised against peripheral blood mononuclear cells gave preparations in which 78-97% of the nucleated cells were erythroid, with a 24-77% recovery. Viability was high, morphology was good and the cells were able to divide and differentiate in culture. No metabolic experiments were carried out but the ferritin content of the erythroblasts was measured in four experiments and found to be about 200-2000 times higher than that found in normal erythrocytes. The H/S ratio was high in both erythroblasts and erythrocytes. Fractionation on the basis of density of two erythroblast preparations, one from a patient with sideroblastic anaemia and one from a patient with megaloblastic anaemia, showed that the most immature erythroblasts contained the highest content of ferritin and that this fell with maturation. The H/S ratio stayed the same or fell with maturation. It was concluded that this method would be valuable for the study of the role of erythroblast ferritin in normal and pathological situations.

Ferritin concentration has been measured in peripheral blood mononuclear cells and in the incubation medium following in vitro culture. Antibodies to both heart and spleen ferritin were used. Mononuclear cells cultured in medium containing about 12 mumol Fe/l accumulate ferritin rapidly with an increase in the heart:spleen ferritin ratio from 3:1 to about 10:1. Higher concentrations of iron (100 mumol/l) produce an even greater effect. The accumulation of ferritin is prevented by the addition of desferrioxamine (2 mmol/l) to the incubation medium. Accumulation of ferritin appears to take place largely in monocytes. Phagocytosis of red blood cells also causes rapid accumulation of ferritin but without any change in the heart:spleen ratio. Small amounts of both spleen and heart type ferritin are released during incubation in an iron containing medium and following phagocytosis of red blood cells. Some concanavalin A binding ferritin is also released suggesting that phagocytic cells may be a source of the concanavalin A binding ferritin found in normal plasma.

Monocytes, lymphocytes and polymorphs were separated from the peripheral blood of normal human subjects. Ferritin concentrations were determined with antibodies to both human spleen and heart ferritins. The heart type ferritin concentration in monocytes was 38.4 +/- 21.6 fg/cell (mean +/- SD), in lymphocytes 8.6 +/- 6.6 fg/cell and in polymorphs 3.2 +/- 2.4 fg/cell. Spleen type ferritin concentrations (fg/cell) were 15.6 +/- 7.0 in monocytes, 6.6 +/- 5.7 in lymphocytes and 7.0 +/- 4.6 in polymorphs. The mean heart/spleen ferritin ratios were 2.8/1 for monocytes, 2.0/1 for lymphocytes and 0.6/1 for polymorphs. The cell extracts were also subjected to anion exchange chromatography. Heart type ferritin eluted at a higher chloride ion concentration than spleen type ferritin. Both H and L subunits were synthesized by mononuclear cells when incubated with 3H-leucine. Human leucocytes contain a wide range of isoferritins and ferritin concentrations may be considerably underestimated in conventional assays for serum ferritin which employ antibodies to liver or spleen ferritin.