On the joint effects of stimulus quality, regularity, and lexicality when reading aloud: New challenges.

A number of computational models have been developed over the last 2 decades that are remarkably successful at explaining the process of translating print into sound. Nevertheless, 2 of the most successful computational accounts on the table fail to simulate the results from factorial experiments reported in this article in which university students read aloud letter strings that varied in terms of spelling–sound regularity and lexicality (regular words vs. exception words vs. nonwords) and stimulus quality (bright vs. dim). Skilled readers yielded additive effects of regularity and stimulus quality and additive effects of lexicality and stimulus quality on both RT and errors when nonwords were mixed with words. When only words appeared in the list, there was an interaction in which exception words were less affected by low stimulus quality than regular words were; no existing account anticipates or explains these results. We advance a hypothesis that assumes a novel module that accommodates these data and provide an existence proof in the form of a simulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors

BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.     

The Costs of Local Food Procurement in Two Northern Indigenous Communities in Canada

Remote Northern Ontario First Nations communities face severe food insecurity. Prices of store foods are often unaffordable and not always in stock. Government programs have been implemented to subsidize some of the market food costs. Our objective is to illustrate the costs associated with procuring food from the land through hunting and fishing in an effort to present this as an alternate option to relying solely on store-bought foods. Northern Ontario is an area of the world undergoing a rapid nutrition transition leading to high levels of obesity and type 2 diabetes. Despite this knowledge, little has been done to reverse this trend using land based foods, widely promoted as nutritionally beneficial. We conclude that estimated cost of food from the land requires significant energy and time, but remains economically comparable to food available in-store. Further government support should be given to community hunters to make land-based food a viable option for a larger proportion of each community.     

Visual word recognition: Evidence for global and local control over semantic feedback.

Two lexical decision experiments examined the joint effects of stimulus quality, semantic context, and cue-target associative strength when all factors were intermixed in a block of trials. Both experiments found a three-way interaction. Semantic context and stimulus quality interacted when associative strength between cue-target pairs was strong, and the interaction was eliminated when the strength was weak. These results support a role for a local mechanism that relies on trial specific information, in addition to a mechanism that makes use of global information available across a block of trials. The absence of an interaction between the joint effects of semantic context and stimulus quality is attributed to blocking the feedback from the semantic system to the orthographic system, functionally separating the orthographic and semantic modules. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.     

When benefits outweigh costs: Reconsidering “automatic” phonological recoding when reading aloud.

Skilled readers are slower to read aloud exception words (e.g., PINT) than regular words (e.g., MINT). In the case of exception words, sublexical knowledge competes with the correct pronunciation driven by lexical knowledge, whereas no such competition occurs for regular words. The dominant view is that the cost of this “regularity” effect is evidence that sublexical spelling-sound conversion is impossible to prevent (i.e., is “automatic”). This view has become so reified that the field rarely questions it. However, the results of simulations from the most successful computational models on the table suggest that the claim of “automatic” sublexical phonological recoding is premature given that there is also a benefit conferred by sublexical processing. Taken together with evidence from skilled readers that sublexical phonological recoding can be stopped, we suggest that the field is too narrowly focused when it asserts that sublexical phonological recoding is “automatic” and that a broader, more nuanced and contextually driven approach provides a more useful framework. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Reading aloud: Evidence for contextual control over lexical activation.

Can readers exert control (albeit unconsciously) over activation at particular loci in the reading system? The authors addressed this issue in 4 experiments in which participants read target words aloud and the factors of prime–target relation (semantic, repetition), context (related, unrelated), stimulus quality (bright, dim), and relatedness proportion (RP; high, low) were manipulated. In the high RP condition (RP = .5), an interaction between semantic context and stimulus quality was observed in which low stimulus quality slowed unrelated targets more than related ones, replicating previous work. In contrast, the low RP condition (RP = .25) yielded additive effects of semantic context and stimulus quality. However, when low RP was examined within the context of repetition priming, context and stimulus quality once again interacted. These results are discussed in the context of a widely endorsed framework with the addition of the central assumption that there is control over feedback between various levels. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Constraints on computational models of basic processes in reading.

There are numerous reports in the visual word recognition literature that the joint effects of various factors are additive on reaction time. A central claim by D. C. Plaut and J. R. Booth (2000, 2006) is that their parallel distributed processing model simulates additive effects of stimulus quality and word frequency in the context of lexical decision. If correct, this success would have important implications for computational accounts of reading processes. However, the results of further simulations with this model undermine this claim given that the joint effects of stimulus quality and word frequency yield a nonmonotonic function (underadditivity, additivity, and overadditivity) depending on the size of the stimulus quality effect, whereas skilled readers yield additivity more broadly. The implications of these results both locally and more globally are discussed, and a number of other issues are noted. Additivity of factor effects constitutes a benchmark that computational accounts should strive to meet. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D-2-deoxyribose and D-arabinose, but not D-ribose, stabilize the cytosine tetrad (i-DNA) structure

Described here are studies exploring the effect of the sugar-phosphate backbone on the stability of i-tetrads in solution [K. Gehring et al. Nature 363, 561-565 (1993)]. In the accompanying paper, branched oligonucleotides are shown to be effective probes for organizing oligodeoxycytidine strands into I-motif structures (C-tetrads). Specifically, the joining of a pair of parallel deoxycytidylate strands with a riboadenosine "linker" leads to marked enhancement in stability of the tetrad structure. To further characterize the nature of the sugar-sugar interactions in this novel structure, branched oligonucleotides containing D-arabinocytidine and D-ribocytidine were synthesized and their association properties examined. The ribo oligomers were prepared in two regioisomeric forms differing only in the connectivities of the deoxycytidine strands, i.e., 3'-to-5' versus 2'-to-5' linked dC5 strands. The branched D-deoxycytidine analogue, rA(2',5'-dC5)3',5'-dC5, which previously has been shown to fold into a bimolecular I-motif, served as model system. It is found that the arabinose substitution leads to hypochromic structures that are characteristic of four-stranded intercalated DNA and has little, if any, effect on the stability of the complex formed. Parallel experiments with the branched ribocytidine analogs gave very weak or no discernible UV transitions, consistent with no strand association in this case [Lacroix et al., Biochemistry 35, 8715-8722 (1996)]. These results are discussed in relation to expected steric interactions of oligocytidine strands within the I-structure. The findings increase our understanding of the impact of the sugar and internucleotide connectivity on the stability of this higher-order nucleic acid structure.