7-day Delay Research Articles

Collection media and delayed freezing effects on microbial composition of human stool.

BackgroundDifferent bacteria in stool have markedly varied growth and survival when stored at ambient temperature. It is paramount to develop optimal biostabilization of stool samples during collection and assess long-term storage for clinical specimens and epidemiological microbiome studies. We evaluated the effect of collection media and delayed freezing up to 7 days on microbial composition. Ten participants collected triplicate stool samples each into no media as well as RNAlater® with and without kanamycin or ciprofloxacin. For each set of conditions, triplicate samples were frozen on dry ice immediately (time = 0) or frozen at −80 °C after 3-days and 7-days incubation at 25 °C. Microbiota metrics were estimated from Illumina MiSeq sequences of 16S rRNA gene fragments (V3–V4 region). Intraclass correlation coefficients (ICC) across triplicates, collection media, and incubation time were estimated for taxonomy and alpha and beta diversity metrics.ResultsRNAlater® alone yielded the highest ICCs for diversity metrics at time = 0 [ICC median 0.935 (range 0.89–0.97)], but ICCs varied greatly (range 0.44–1.0) for taxa with relative abundances <1 %. The 3- and 7-day freezing delays were generally associated with stable beta diversity for all three media conditions. Freezing delay caused increased variance for Shannon index (median ICC 0.77) and especially for observed species abundance (median ICC 0.47). Variance in observed species abundance and in phylogenetic distance whole tree was similarly increased with a 7-day delay. Antibiotics did not mitigate variance. No media had inferior ICCs at time 0 and differed markedly from any media in microbiome composition (e.g., P = 0.01 for relative abundance of Bacteroidetes).ConclusionBacterial community composition was stable for 7 days at room temperature in RNAlater® alone. RNAlater® provides some stability for beta diversity analyses, but analyses of rare taxa will be inaccurate if specimens are not frozen immediately. RNAlater® could be used as collection media with minimal change in the microbiota composition.

Effect of Delayed Bonding and Antioxidant Application on the Bond Strength to Enamel after Internal Bleaching.

This study evaluated the effect of delayed bonding and antioxidant application (AA, 10% sodium ascorbate) after internal bleaching (35% carbamide peroxide) on the shear bond strength of an adhesive cement to enamel. Eighty-four human maxillary central incisors were endodontically treated. The control group remained unbleached with no AA. Experimental groups were all internally bleached. The buccal enamel was finished and polished with metallographic paper to a refinement of #600, in order to obtain a 5-mm(2) flat bonding area. An adhesive cement (Clearfil Esthetic) was placed into a plastic tube with internal diameter of 3 mm and a 3-mm height and cured on the enamel. Bonding occurred either immediately after bleaching (group Im), a 7-day delay (group 7), or a 14-day delay (group 14), and half the specimens were treated with antioxidant application (groups Im-AA, 7-AA, and 14-AA). Shear bond strength testing was performed on a universal testing machine, and data were analyzed with ANOVA and Fisher test (5%). Delaying of bonding is a useful factor for enhancing shear bond strength (p < 0.05), whereas AA only enhanced shear bond strength after 7 days delayed bleaching (p < 0.05). The highest bond strength was noted in groups 7-AA (20.51 ± 4.5 MPa), 14 (19.82 ± 4.6), 14-AA (20.27 ± 4.4), and control (20.51 ± 5.1), which were not significantly different from each other. After internal bleaching, adhesive cementation to enamel is recommended only when delayed 14 days, or delayed 7 days with sodium ascorbate application.

Effects of glyphosate-based herbicides on survival, development, growth and sex ratios of wood frogs (Lithobates sylvaticus) tadpoles. I: Chronic laboratory exposures to VisionMax®

The purpose of this study was to determine if chronic exposure to the glyphosate-based herbicide VisionMax® affects the survival, development, growth, sex ratios and expression of specific genes involved in metamorphosis of wood frog tadpoles (Lithobates sylvaticus). We hypothesized that exposure to this herbicide will affect developmental rates by disrupting hormone pathways, sex ratios and/or gonadal morphology. Tadpoles were chronically exposed in the laboratory from Gosner developmental stage 25 to 42 to four different concentrations of VisionMax® (ranging from 0.021 to 2.9mg acid equivalents/L). Chronic exposures to VisionMax® had direct effects on the metamorphosis of L. sylvaticus tadpoles by decreasing development rates, however, there was a decrease in survival only in the group exposed to the highest dose of VisionMax® (2.9mga.e./L; from approximately 96% in the control group to 77% in the treatment group). There was a decrease in the number of tadpoles reaching metamorphic climax, from 78% in the control group to 42% in the VisionMax® (2.9mga.e./L) group, and a 7-day delay to reach metamorphic climax in the same treatment group. No effects of exposure on sex ratios or gonadal morphology were detected in tadpoles exposed to any of the concentrations of VisionMax® tested. Gene expression analyses in brain and tail tissues demonstrated that exposure to VisionMax® alters the expression of key genes involved in development. Results showed significant interaction (two-way ANOVA, P<0.05) between developmental Gosner stage and treatment in brain corticotropin-releasing factor, deiodinase type II (dio2) and glucocorticotiroid receptor (grII) and tail dio2 and grII. This demonstrates that mRNA levels may be differently affected by treatment depending on the developmental stage at which they are assessed. At the same time there was a clear dose–response effect for VisionMax® to increase thyroid hormone receptor β in tadpole brain (F(2,69)=3.475, P=0.037) and tail (F(2,69)=27.569, P<0.001), regardless of developmental stage. Interestingly, delays in development (or survival) were only observed in the group exposed to 2.9mga.e./L of VisionMax®, suggesting that tadpoles need to be exposed to a “threshold” concentration of glyphosate-based herbicide to exhibit phenotypic observable effects. We suggest that the upregulation of genes that trigger metamorphosis following VisionMax® herbicide exposure might result from a compensatory response for the delays in development observed. Further studies are needed to determine if disruption of expression of these key genes leads to long-term effects when metamorphs reach adult stages.

Accelerated long-term forgetting in children with temporal lobe epilepsy

Adults with temporal lobe epilepsy (TLE) have been found to have accelerated long-term forgetting, but this phenomenon has not yet been investigated in children. Although deficits in recall of materials after short (20- to 30-minute) delays have been shown to slowly emerge from childhood to adolescence in patients with TLE, it is unknown whether such a trend will also be found in recall of materials after long delays. This study examined the presence of accelerated long-term forgetting in children with TLE and how it relates to chronological age. Twenty-three children with TLE and 58 healthy controls of similar age, sex distribution and socioeconomic status completed a battery of neuropsychological tests, including standardised tests of story recall and design location, as well as two experimental tests requiring the learning of words and design locations to a criterion, both of which assessed recall after short (30-min) and long (7-day) delays. Word recall at the 7-day delay (relative to the 30-min recall) was significantly poorer in the TLE group, compared to the control group. The TLE group also exhibited worse 30-min recall performance on a standardised test of story recall. Individual patient analyses revealed dissociation between performance on the experimental and standardised verbal memory tests; children who were impaired on the experimental test (7-day delay) were not impaired on the standardised test (30-min delay). Compared to controls, patients with a left-hemisphere seizure focus recalled fewer words at short and long delays while patients with an abnormal hippocampus recalled fewer words at the long delay. No between-group differences were found with respect to the design location task. Age negatively correlated with the recall of words after short- and long-term delays within the TLE group, where older age was associated with worse memory. This association was not present in the control group. To our knowledge, this is the first study to show evidence of accelerated long-term forgetting in children with TLE, which could not be explained by poor performance on standardised memory tests. Additionally, these results suggest that the developmental trajectory of long-term memory in children with TLE is similar to that of short-term memory: deficits emerge gradually, therefore older children are more likely to present with long-term memory deficits.

Abstract W P99: A Time Window of Heightened Plasticity to Training After Ischemic Stroke in the Mouse is Extended By Fluoxetine if Provided Within the First Week After Stroke

Background: and purpose - Data in humans and in non-human animal models suggest that most recovery from motor impairment occurs in the first 4 weeks after stroke and is mediated in part by increased responsiveness to training in this short time period. We tested the hypothesis that there is a gradient of diminishing responsiveness to training in the first week after stroke in the mouse. We then tested whether fluoxetine can extend the time window over which large training-related gains can be expected. Methods: Adult C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke or sham stroke in the caudal forelimb area (CFA can be considered rodent primary motor cortex). The mice were then retrained after a 1- or 7-day delay in the presence or absence of fluoxetine injected IP daily beginning after a 1- or 7-day delay. Results: Training-associated recovery of prehension was complete if training was initiated after a 1-day delay but incomplete if training was initiated after a 7-day delay, even with additional training days. Daily fluoxetine administration after stroke was associated with complete recovery of prehension even if training was delayed 7 days but only if fluoxetine was administered beginning 1 day but not 7 days after stroke. Conclusions: We conclude that there is a sensitive period 7 days after stroke during which motor training is more likely to promote recovery and that this period can be extended by fluoxetine only if administration begins during the first week after stroke. Our mouse model, with all of the attendant genetic benefits, may allow us to determine at the cellular and molecular level how behavioral training and endogenous plasticity interact to mediate recovery.

Why does lag affect the durability of memory-based automaticity: Loss of memory strength or interference?

In Rickard, Lau, and Pashler's (2008) investigation of the lag effect on memory-based automaticity, response times were faster and proportion of trials retrieved was higher at the end of practice for short lag items than for long lag items. However, during testing after a delay, response times were slower and proportion of trials retrieved was lower for short lag items than for long lag items. The current study investigated the extent to which the lag effect on the durability of memory-based automaticity is due to interference or to the loss of memory strength with time. Participants repeatedly practiced alphabet subtraction items in short lag and long lag conditions. After practice, half of the participants were immediately tested and the other half were tested after a 7-day delay. Results indicate that the lag effect on the durability of memory-based automaticity is primarily due to interference. We discuss potential modification of current memory-based processing theories to account for these effects.

Accelerated long‐term forgetting in children with idiopathic generalized epilepsy

The rapid forgetting of information over long (but not short) delays (accelerated long-term forgetting [ALF]) has been associated with temporal lobe epilepsy but not idiopathic generalized epilepsy (IGE). Long-term memory formation (consolidation) is thought to demand an interaction between medial temporal and neocortical networks, which could be disrupted by epilepsy/seizures themselves. The present study investigates whether ALF is present in children with IGE and whether it relates to epilepsy severity. Sixty-one children (20 with IGE and 41 healthy controls [HC]) of comparable age, sex, and parental socioeconomic status completed neuropsychological tests, including a measure of verbal learning and recall after, short (30-min) and long (7-day) delays, and recognition. Epilepsy severity was rated by treating neurologists. A two-way repeated measures analysis of covariance (ANCOVA) found a significant Group x Delay interaction; the children with IGE recalled (and recognized) significantly fewer words after a long, but not short (2- and 30-min) delay relative to the HC children. Moreover, greater epilepsy severity was associated with poorer recognition. This study demonstrates, to our knowledge for the first time, that children with IGE present with ALF, which is related to epilepsy severity. These findings support the notion that epilepsy/seizures themselves may disrupt long-term memory consolidation, which interferes with day-to-day functioning of children with IGE.

The response of summer monsoon onset/retreat in Sumatra-Java and tropical Australia region to global warming in CMIP3 models

In this study, we assess the potential changes in the onset, retreat and duration of austral summer monsoon covering the domain from south Sumatra and Java region in the tropics to the northern Australian continent. We simply call it the Australian summer monsoon. Daily precipitable water and 850 hPa wind from 13 CMIP3 models are used in the diagnoses. A majority of the models can capture the northwest–southeast evolution of the summer monsoon, which starts from the south Sumatra and Java region around later November and then progressively approaches the Australian continent in late December. Nevertheless, significant biases exist in the modeled onset/retreat dates and the extent of the monsoon inland penetration. Under global warming, the agreement among the model projections varies across the domain. In between the Sumatra-Java archipelago and the top end of the Australian continent, over 80 % of the models simulate delayed monsoon onset and shortened duration by ~10 days, but less model agreement is seen over interior continent where the model ensembles show an approximate 7-day delay of both the onset and retreat with relatively little change in duration. Both El Nino-Southern Oscillation and Indian Ocean SST patterns appear to play important roles in determining the variations of the modeled monsoon onset. Nevertheless, the extent of their influence varies significantly across the models. Under global warming, a large proportion of models show relatively less warming in the eastern Indian Ocean and with a consequent increase in the modeled Indian Ocean Dipole index. Both a weakened and/or eastward shift of the upward branch of Walker circulation and the Indian Ocean contribute to the simulated delayed onset and shortened duration in the tropics under global warming.

Effects of flaxseed oil supplementation and FADS genotype on declarative memory abilities in toddlers

ObjectiveDocosahexaenoic acid (DHA) is integral to neuronal function and subsequent cognition. Biosynthesis of DHA from its precursor alpha‐linolenic acid (LNA) is controlled by the FADS gene complex. Previously unobserved genetic differences may be a confound in studies of biosynthesis. This intervention was designed to determine the cognitive effects of providing substrate (flaxseed oil) to a system with little exogenous DHA intake (human toddlers).Methods16‐month‐olds (n=65) were enrolled in a 4‐month double‐blind intervention and randomized to flaxseed or corn oil. Parents squeezed 2400 mg of oil into their toddlers’ food daily for 180 days. Memory was assessed at 0, 7, 180, and 187 days using a non‐verbal declarative memory paradigm. Toddlers were exposed to 4 new imitation events and were tested for memory immediately, after 20 min, and after 7 days at baseline and end (total events = 8). Genotype at rs174575 on the FADS2 gene was determined.ResultsBaseline, 20‐min delay, and 7‐day delay results indicate no differences in memory performance when analyses are based on participant genotype. However, when analyses are completed with maternal genotype, children of homozygous recessive mothers earned lower scores on the memory tasks.ConclusionMaternal genotype needs to be considered instead of or in addition to the participants’ genotypes when assessing the effects of fatty acid supplementation.

The First-Perspective Alignment Effect: The Role of Environmental Complexity and Familiarity with Surroundings

People often remember relatively novel environments from the first perspective encountered or the first direction of travel. This initial perspective can determine a preferred orientation that facilitates the efficiency of spatial judgements at multiple recalled locations. The present study examined this "first-perspective alignment effect" (FPA effect). In three experiments, university students explored three-path routes through computer-simulated spaces presented on a desktop computer screen. Spatial memory was then tested employing a "judgement of relative direction" task. Contrary to the predictions of a previous account, Experiment 1 found a reliable FPA effect in barren and complex environments. Experiment 2 strongly implicated the importance of complete novelty of the space surrounding the route in producing the effect. Experiment 3 found that, while familiarity with the surrounding space greatly attenuated the FPA effect with immediate testing, the effect reemerged following a 7-day delay to testing. The implications for the encoding and retrieval of spatial reference frames are discussed.

Counterconditioning

The evidence for the effectiveness of counterconditioning as a strategy for changing conditioned preferences is rather scarce and inconclusive. The present experiment reinvestigated this issue and compared the effect of further conditioning, extinction, and a counterconditioning procedure on recently acquired conditioned preferences in a picture-taste paradigm. Self-report and affective priming data indicated that whereas further conditioning and extinction trials were ineffective in fully eliminating the previously acquired evaluations, the counterconditioning treatment did succeed in doing this. A follow-up valence assessment revealed that all these effects persisted after a 7-day delay period.

Testing the limits of testing effects using completion tests

Recent work on testing effects has shown that retrieval practice can facilitate memory even for complex prose materials (Roediger & Karpicke, 2006a, 2006b). In three experiments the current study explores the effectiveness of retrieval practice on fill-in-the-blank (FITB) tests requiring the recall of specific words or phrases from a text. Final tests included both repeated items that were directly taken from initial tests, and related items. In Experiment 1, with a 2-day delay between initial and final tests, FITB testing benefited performance only on repeated items. In Experiment 2 a 7-day delay between testing sessions led to more robust effects on repeated items. However, once again no benefits were seen for related items. In Experiment 3 the scope of retrieval was varied by comparing FITB tests to paragraph recall tests requiring retrieval of all sentences following a topic sentence. Only the more open-ended recall practice demonstrated improvements in transfer to novel questions. The results suggest that scope or type of processing required during retrieval practice is likely a critical factor in whether testing will have specific or robust benefits.

Episodic feeling-of-knowing resolution derives from the quality of original encoding.

In recent studies, researchers have argued for adult age-related deficits in the resolution of episodic feeling of knowing (FOK) owing to a decline in inferential processes. In the present study, we introduce the memory constraint hypothesis, which argues that deficits are an outcome of differences in the level of learning. A repetition delay paradigm for a list of paired-associate items showed that repeated presentations at encoding increased memory performance and in turn increased FOK resolution for unrecalled items. Older adults who were given a 48-h delay between encoding and subsequent tests (and FOKs) had equivalent memory performance to younger adults who were given a 7-day delay. In this case, age equivalence arose in FOK resolution except at the lowest levels of recognition in the single-presentation condition. The use of effective strategies during encoding correlated with memory performance and FOKs, even for unrecalled pairs. These results are inconsistent with an inferential-deficit explanation of age deficits in FOK resolution; they point to the importance of original encoding quality as a potent contributor to FOK resolution, and they argue for equating age groups on memory performance when evaluating the episodic FOK resolution of age differences.

Delayed Treatment Effects of Xanthine Oxidase Inhibition on Systolic Overload-Induced Left Ventricular Hypertrophy and Dysfunction

The nonpurine selective xanthine oxidase (XO) inhibitor febuxostat attenuates development of left ventricular (LV) hypertrophy and dysfunction in mice when treatment is initiated within 1 hour of transverse aortic constriction (TAC). This study investigated whether a 7-day delay of treatment with the XO inhibitors febuxostat or allopurinol would reverse TAC-induced changes after onset of heart failure (HF). Neither treatment significantly affected TAC-induced LV hypertrophy; only febuxostat caused a modest improvement in LV function (∼10% increase in LV ejection fraction). However, the purine analog allopurinol tended to increase mortality compared with vehicle or febuxostat in HF mice.

Pegylated liposomal doxorubicin for adjuvant treatment of breast cancer in patients refusing therapy with conventional doxorubicin.

e11097 Background: Doxorubicin is a drug of primary importance in the adjuvant chemotherapy of breast cancer. The most frequent side effects besides myelotoxicity are alopecia and cardiotoxicity. The latter influences the treatment plan in pts candidated to treatment with potentially cardiotoxic drugs such as trastuzumab. Recently, women have a stronger consciousness on therapeutic options and theray-related side effects, due to improved access to press or internet, and ask the physician for less toxic treatment, to avoid cardiotoxicity and alopecia, due to availability of liposomal doxorubicin, less cardiotoxic (Doxil, Myocet) and devoid from effects on hair loss (Doxil). Liposomal doxorubicin is not a standard treatment for adjuvant CT in breast cancer. We report on our experience of use of Doxil (PLD) due to clear patient request. Methods: From June 2007 to December 2009, 30 patients have been treated with PLD. The reasons for this choice are: refusal of the risk of alopecia in 11 pts; refusal of the risk of cardiotoxicity in 13 pts; a treatment plan implying the use of trastuzumab in 6 pts. Median age was 47 (26-62); ECOG PS = 0; breast cancer stage I and II; 19 pts with N1 disease (2 with more than 3 positive nodes); 24 pts hormone receptor +; 7 pts HER-2 +. CT schedules: FDC (5-FU 600 mg/m2, Doxil 35 mg/m2, CTX 600 mg/m2) in 23 pts; DC (Doxil 40 mg/m2, CTX 600 mg/m2) in 7 pts. Results: All the pts have completed the CT for a total of 160 courses (6 courses in 19 pts; 4 courses in 11 pts), without any dose reduction, but with a 7-day delay in 32 courses due to grade 3 neutropenia. Alopecia G1 was observed in 1 pt and G2 in 2 pts. The most frequent side- effect has been Hand Foot Syndrome (HFS): G1 in 12 cases; G2-G3 in 16 cases; G3-G4 in 2 pts. We did not observed any cardiac dysfunction, evaluated through echocardiography. At the present time all the pts are alive, but 2 of them show progressive disease. Conclusions: Our data show that Doxil-based chemotherapy in the adjuvant setting is feasible, with an toxicity similar to that observed with conventional doxorubicin. Alopecia was sporadic and mild. We did not observed cardiotoxicity. HFS is the most frequent side effect, it was mild to moderate and easily manageable. No significant financial relationships to disclose.

Characterization of Some Molecular Mechanisms Governing Autoactivation of the Catalytic Domain of the Anaplastic Lymphoma Kinase

NPM/ALK is an oncogenic fusion protein expressed in approximately 50% of anaplastic large cell lymphoma cases. It derives from the t(2;5)(p23;q35) chromosomal translocation that fuses the catalytic domain of the tyrosine kinase, anaplastic lymphoma kinase (ALK), with the dimerization domain of the ubiquitously expressed nucleophosmin (NPM) protein. Dimerization of the ALK kinase domain leads to its autophosphorylation and constitutive activation. Activated NPM/ALK stimulates downstream survival and proliferation signaling pathways leading to malignant transformation. Herein, we investigated the molecular mechanisms of autoactivation of the catalytic domain of ALK. Because kinases are typically regulated by autophosphorylation of their activation loops, we systematically mutated (Tyr --> Phe) three potential autophosphorylation sites contained in the "YXXXYY" motif of the ALK activation loop, and determined the effect of these mutations on the catalytic activity and biological function of NPM/ALK. We observed that mutation of both the second and third tyrosine residues (YFF mutant) did not affect the kinase activity or transforming ability of NPM/ALK. In contrast, mutation of the first and second (FFY), first and third (FYF), or all three (FFF) tyrosine residues impaired both kinase activity and transforming ability of NPM/ALK. Furthermore, a DFF mutant, in which the aspartic residue introduces a negative charge similar to a phosphorylated tyrosine, possessed catalytic activity similar to the YFF mutant. Together, our findings indicate that phosphorylation of the first tyrosine of the YXXXYY motif is necessary for the autoactivation of the ALK kinase domain and the transforming activity of NPM/ALK.

Phase I study of weekly nedaplatin and concurrent pelvic radiotherapy as adjuvant therapy after radical surgery for cervical cancer

Nedaplatin is an analog of cisplatin that was developed in Japan, and it exhibits less nephrotoxicity, neurotoxicity, and gastrointestinal toxicity than cisplatin. This study aimed to determine the recommended dose of weekly nedaplatin chemoradiotherapy in high-risk patients following radical surgery. Fifteen patients who required postoperative pelvic radiotherapy after radical surgery for cervical cancer were enrolled in the present study. Nedaplatin was designed to be administered for eight cycles (minimum five cycles) beginning at a weekly dose of 22.5 mg/m(2) and then escalating to 25, 27.5, and then to 30 mg/m(2). Dose-limiting toxicity was defined as a more than 7-day delay in the planned radiation therapy and/or planned chemotherapy (prior to the completion of five cycles) due to toxicity. Nedaplatin administration was interrupted prior to the completion of five cycles in one of six patients at a dose of 27.5 mg/m(2). A more than 7-day delay in the planned radiation therapy did not occur in any patient. Nedaplatin at a dose of 30 mg/m(2) was safely administered, and two of three patients could receive the planned chemotherapy consisting of eight cycles of weekly nedaplatin. Our recommended weekly nedaplatin dose was determined to be 30 mg/m(2) administered for more than five cycles and up to eight cycles if possible. Weekly administration of nedaplatin may be more tolerable and less toxic than weekly administration of cisplatin.

Phase I study of chemoradiation with nedaplatin and ifosfamide in patients with advanced squamous cell carcinoma of the uterine cervix

Cisplatin and ifosfamide are considered among the most active drugs in both neoadjuvant and salvage treatments for patients with cervical cancer. Nedaplatin is an analog of cisplatin and it exhibits lesser nephrotoxicity, neurotoxicity, and gastrointestinal toxicity than cisplatin. This study aimed to determine the recommended dosage of nedaplatin plus ifosfamide chemoradiotherapy for advanced squamous cell carcinoma (SCC) of the uterine cervix. Beginning with a dose of 65 mg/m(2), nedaplatin (day 1) combined with ifosfamide 1 g/m(2) (days 1-5) was designed to be administered for three cycles (minimum: two cycles); its dose was gradually escalated up to 80 mg/m(2). Dose-limiting toxicity (DLT) was defined as a more than 7-day delay in the planned radiation therapy and/or planned chemotherapy (prior to the completion of two cycles) due to toxicity. Chemotherapy was not interrupted prior to the completion of two cycles in any patients. Of the 12 patients, 11 received three cycles of chemotherapy. DLT did not occur in any patient. We confirmed a clinical complete response (CR) in ten and partial response (PR) in two patients. The median follow-up period was 39 months (range: 18-57 months). Ten patients (83%) were alive and disease free, one patient was alive with disease, and only one patient died due to the disease. Nedaplatin and ifosfamide combination chemotherapy is a feasible and active chemoradiation strategy for patients with advanced SCC of the uterine cervix. With the ifosfamide dose fixed to 1 g/m(2), the recommended nedaplatin dosage was determined to be 80 mg/m(2) to be administered for three cycles.

Understanding developmental changes in the stability and flexibility of spatial categories based on object relatedness.

Two experiments examined the flexibility and stability with which children and adults organize locations into categories on the basis of object relatedness. Seven-, 9-, and 11-year-olds and adults learned the locations of 20 objects belonging to 4 categories. Displacement patterns revealed that children and adults used object cues to organize the locations into groups. The organization remained the same following a 7-day delay for all 4 ages, demonstrating stability. Moreover, for 11-year-olds and adults, this organization shifted after a new pattern of object-location pairings was introduced. The pattern was less clear for the younger children, suggesting that flexibility increases across childhood. Discussion focuses on the dynamics of organization processes, particularly stability and flexibility, and the integration of objects and locations.

Is time-based prospective remembering mediated by self-initiated rehearsals? Role of incidental cues, ongoing activity, age, and motivation.

The present research examined self-reported rehearsal processes in naturalistic time-based prospective memory tasks (Study 1 and 2) and compared them with the processes in event-based tasks (Study 3). Participants had to remember to phone the experimenter either at a prearranged time (a time-based task) or after receiving a certain text message (an event-based task) and record the details of occasions when they thought about this intention during a 7-day delay interval. The rehearsal and retrieval of time-based tasks was mediated by more automatic than deliberate self-initiated processes. Moreover, the number of reported rehearsals without any apparent triggers was reliably higher in time- than in event-based tasks. Additional findings concern the effects of age, motivation, and ongoing activities on rehearsal and prospective memory performance.