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Background: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). Methods: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay. Results: Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control. Conclusion: The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers. General significance: There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.

Background: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). Methods: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay. Results: Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control. Conclusion: The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers. General significance: There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.

The required speed of response is one of the many dimensions along which tasks vary. Although it is well-known that, in general, as the speed of a task increases, proficiency of performance decreases, the relationship between the performance of a first and second task as a function of the difference in their speed requirements is not so well known. For optimal performance of a second task there must be some best speed of the first or training task. At present, however, the specification of the speed for the optimal training task (for any given second task) must be based upon speculation unsupported by reliable data. The study being reported was designed to obtain information on the general problem of the influence of the speed of a training task upon the performance of a following task. The task used in the research was rotary pursuit at four different speeds. The speeds were assigned to the training and transfer periods in such a manner as to obtain all 16 possible combinations of speeds in the two periods. The 16 different combinations of speeds were presented under three different conditions of distribution of practice; thus, a total of 48 subgroups were employed in the experiment.

Five versions of an instructional program on medical terminology were experimentally evaluated to determine the effect of redundancy or repetition on learning. The subjects were assigned to five groups. A different instructional mode was administered to the subjects in each group. The modes contained identical terminal behaviors, and a 79-item multiple-choice test, which exhausted the population of behaviors, served as the achievement criterion. (Author), Presented at the Annual Meeting of the Midwestern Psychological Association, Chicago, Ill., 2 May 68.

The study compared three methods of instruction in binary and octal arithmetic, i.e., (1) Norman Crowder's branched programed text, The Arithmetic of Computers, (2) another version of this text modified so that subjects could not see the instructional material while answering 'branching' questions, and (3) a narrative text version presenting the same content material. The principal behavioral measure was relative performance on a pre- and posttraining criterion test. The results indicated that prohibiting visual contact with instructional material while answering questions significantly increased the number of erroneous alternatives selected by the subjects, but did not significantly alter the amount of learning manifested nor the time necessary to complete training. The programed instructional methods resulted in significantly greater improvement on the criterion test than was attained by using the narrative text. The time to complete instruction was significantly less with the narrative text version of the material. Although, in general, less informational content was imparted with the narrative text, the study time necessary per unit improvement was significantly less with that version. Records were kept of the number of 'wrong answer' branches taken by the subjects receiving instruction via the branched programs. Only about 6% of the total possible 'wrong' branches were actually taken. This suggests that branched programing may be wasteful by virtue of providing a quantity of material that is never studied. (Author)

The effects of repetition and spaced review in programed instruction were studied. Experiments 1 and 2 covered a one-semester course in General Science at the Junior High School level. In Experiment 3, a 1280-frame portion of the total course was used. In Experiments 1 and 2, comparisons were made among (a) a conventional course, (b) a regular linear version of the program, and (c) a spiral version of the program. The results indicate that the programed course was at least as effective as the conventional instruction in terms of both learning and retention after 15 weeks. The linear program was superior to conventional instruction on some measures. The spiral program offered few, if any, advantages over the regular linear program. Experiment 3 allowed a more precise evaluation of the separate effects of repetition and spaced review. Spaced review produced significant increases in learning which persisted, and even increased, through a 3-week retention interval. Repetition did not produce increased learning or retention. The general conclusions are: (a) repetition of instructional materials above the usual level in a linear program is not beneficial; (b) spaced review is potentially beneficial; and (c) some techniques of obtaining spaced review, eg, spiral programing, may offer disadvantages that equal or outweigh the potential advantages of spaced review. (Author)

This experiment investigated the effects of degree of learning of a first task and degree of similarity between two tasks on the transfer of training from the first to the second task. The basic relationship between the two tasks was such that learning the first might well interfere with learning the second. Twelve groups of 15 college students learned a symbol substitution task to one of four levels of mastery. They were then transferred to a task where the symbols in task I were rearranged to permit three degrees of intertask similarity. Extensive and persistent negative transfer was obtained. During the initial stages of learning task II, negative transfer seemed to decrease as the degree of learning of task I increased. However, during the later stages of task II, negative transfer seemed to increase with an increase in the degree of learning of the first task, especially with the higher degrees of learning of task I. The intertask similarity variable appeared to be significant only during the early stages of learning the second task. These findings differ from previous findings in the extent and persistence of negative transfer and in the tendency for it to increase with higher degrees of first task mastery. The present findings question the generality of existing transfer principles derived from slowly paced tasks involving relatively few discrete stimuli and responses. (Author), Ohio State Univ., Columbus, Research Foundation, Contract AF33 038 5474.