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PubMed2003

Children's attentional skills 2 years post-traumatic brain injury.

This study examined sustained attention abilities 24 months postinjury, in 3 groups of children who had suffered a traumatic brain injury (TBI): (a). mild TBI (n = 24), (b). moderate TBI (n = 31), and (c). severe TBI (n = 14). Three manipulations of the traditional Continuous Performance Test paradigm (CPT) were employed in the study, to delineate factors that might influence CPT performance, including speed of processing, attentional lapses, and stimulus complexity. No significant differences were evident among the TBI groups on a measure of simple reaction time, nor on a CPT version where the interstimulus interval was lengthened. However, there was a significant difference between the mild and severe TBI groups on the most complex task, which required speed, accuracy, and decision making, suggesting that these factors underlie impaired performances previously identified on the CPT in children with severe TBI. These findings have implications for the development of intervention programs for these children.

Attention↗

PubMed1993

Diagnosing the cause of recurrent and persistent pneumonia in children.

It is very important to note that safe and effective treatment of recurrent or persistent pneumonia in children is based on firmly establishing an etiologic diagnosis. Empiric treatment using repeated courses of antibiotics and hope is unlikely to yield cure or even good control of most of these processes and is likely to result in more cost to the patient's health and pocketbook. Applied in a staged and systematic way, the diagnostic tools currently available should enable the clinician caring for children to diagnose most of their patients with recurrent or persistent pneumonia. Consultation with a pediatric pulmonologist will generally speed the process and help with difficult or confusing cases. Because effective therapy is available but differs greatly from one etiology to another, early accurate etiologic diagnosis is extremely important. The prognosis for those with asthma generally is very good. But, delay in diagnosis of other causes of recurrent or persistent pneumonia can lead to irreversible pulmonary structural damage that ultimately can only be treated by lung transplantation, if at all.

Child↗

PubMed1993

Neuropsychologic functioning of human immunodeficiency virus-infected children with hemophilia.

Efforts to detect subtle but objective neuropsychologic deficits could clarify the early involvement of the central nervous system and the progression of human immunodeficiency virus (HIV) infection in older children and young adolescents. Baseline examinations of 63 children and adolescents with hemophilia were conducted by examiners unaware of HIV status or staging or of our study's major hypotheses. They measured six domains of neuropsychologic functioning (motor, language, memory, attention, visual processing, and problem solving), and no differences between groups of similar age, race, and socioeconomic status defined by HIV seropositivity (n = 25) and HIV seronegativity (n = 38) were revealed. A high incidence of subtle neuropsychologic deficits relative to (1) age norms and (2) individual cognitive potential was found on measures of motor performance, attention, and speeded visual processing within both infected and uninfected groups. On the basis of these baseline data, it seems premature to attribute early, subtle neuropsychologic deficits in seropositive children with hemophilia to the central nervous system effects of HIV infection.

Adolescent↗

PubMed1998

The effect of presentation rate on serial memory in young children with specific language impairment.

The study examined the serial memory ability of a group of preschool children with specific language impairment (SLI) who were compared to age and language control groups. The children were asked to recognize serial patterns under short and long presentation durations. The subjects were presented with images of common objects (that appeared to be easily recoded into a phonological form) and iconic images of scribble drawings and unfamiliar faces (that did not appear to invite recoding). Under long presentation conditions, the performance of children with SLI resembled that of their age-matched peers on all 3 types of tasks. However, under short presentation conditions, children with SLI performed worse than their age-matched peers on all 3 tasks (and similarly to their language-matched peers). The performance of the children with SLI declined dramatically in all conditions when the items were presented for a brief period. If the serial memory deficits of young children with SLI were specific to phonological processing, their performance on recognizing the pattern of common objects should have been impaired, but not their performance with other visual tasks that are less likely to be recoded. Instead, serial memory in children with SLI was affected by presentation duration across tasks. The findings suggest that recognizing serial patterns is dependent, in part, on the speed of processing serial information. The findings are discussed in relation to models of limited capacity processing.

Child↗

PubMed1998

Neural plasticity in the dynamics of human visual word recognition.

Repeated exposure to words leads to plastic changes in the nervous system throughout the lifespan, with the consequence that common words are processed more rapidly and accurately than rare words. Most behavior time measures correlate highly with the logarithm of a stimulus word's experiential frequency. Here, we demonstrate similar but earlier changes in the latency of a brain-generated evoked potential recorded over the left anterior scalp as individuals silently read sentences. We conclude that experience can speed the processing of some words by at least 50 ms within the first 335 ms of visual processing.

Brain↗

PubMed2000

Rapid hot dog surface pasteurization using cycles of vacuum and steam to kill Listeria innocua.

The vacuum/steam/vacuum surface pasteurization process was applied to hot dogs inoculated on the surface with non-pathogenic Listeria innocua. Using the optimum conditions previously found for processing chicken carcasses as a starting point, optimum process conditions were determined for a hot dog treatment compatible with current process line speed. Cycling the treatment significantly improved the microbiological kill. At the optimum conditions of steam time of 0.3 s at 138 degrees C (two cycles), a bacteria kill >3 log CFU/ml was attained. Pasteurization, frequently considered to be a kill of >5 log CFU/ml, was reached by increasing the number of cycles to three. The surface pasteurization process should ensure that hot dogs reaching the consumer are free of Listeria.

Animals↗

PubMed1999

The NCI All Ireland Cancer Conference.

The National Cancer Institute (NCI) has recently decided to embark on an international partnership with the developing cancer programs on the Island of Ireland (Northern Ireland and the Republic of Ireland) in an attempt to further improve the quality and range of cancer services available for patients. This Transatlantic Partnership called the All Ireland-NCI Cancer Consortium offers exciting opportunities in cancer treatment, education and research as the cancer-caring communities from both the Republic of Ireland and Northern Ireland prepare to join with the U.S. NCI in this major endeavor. The inaugural event of the partnership will be the NCI All Ireland Cancer Conference to be held in Belfast, October 3-6, 1999. (See www.allirelandcancer.com, for information on the conference.) Cancer is a significant cause of mortality and morbidity on the Island of Ireland. There are approximately 28,000 new cases and approximately 11,000 deaths from cancer each year. Therefore, Northern Ireland and the Republic of Ireland have among the highest cancer incidence and mortality rates in the Western World. In recent years there has been a major restructuring of cancer services in both parts of the Island. This is the result of several government reports such as the Campbell Report in Northern Ireland and the National Strategy Document for Cancer in the Republic of Ireland. The National Strategy Document proposes that cancer treatment services should be centered around primary care services, regional services, supra-regional centers and a national coordinating structure whereby the supra-regional centers deliver specialist surgery, medical and radiation oncology, rehabilitation and specialist palliative care. Three supra-regional cancer centers are being established in the cities of Dublin, Cork and Galway and a National Cancer Forum, which has served as a multidisciplinary advisory board to the Government, has pushed the development and implementation of this plan. This has already resulted in a major expansion in the number of medical oncologists practicing in Ireland but further development is required to facilitate multidisciplinary care, to establish programs of education and training and to harness the scientific talent available to engage in the international effort against cancer. In Northern Ireland the Chief Medical Officer commissioned a report entitled "Cancer Services-Investing for the Future" whose key recommendations were that Northern Ireland should have one cancer center in Belfast and four smaller cancer units. This report also recommended the implementation of a multidisciplinary approach to cancer diagnosis, treatment and palliative care. As in the Republic, all the recommendations of the Report have been accepted and the planning and implementation of this plan are now well under way. Therefore, development of services for cancer patients is a top priority for both governments on the Island and, given the process of cancer service development, it is timely to bring international expertise such as the NCI on board as partners in this effort. The decision by the NCI to develop an agreement for cancer research and service development in Ireland is a major boost for those involved in cancer care and research and will, no doubt, help speed the process of redevelopment. There have already been several visits from senior NCI personnel to Ireland including Dr. Klausner, the Director of the NCI, to determine the potential impact of this agreement and to identify the most productive areas of interaction between the NCI and the Irish Cancer Community. As a result of these visits, the NCI has decided to focus on several areas of strategic importance whose objectives will be to enhance clinical services, improve patient care, promote North South collaboration and cement strategic Ireland-U.S. collaboration in cancer research and development. The agreement will build on existing informal links in U.S.-Irish scientific, medical education and training and also promote clinical trials and cancer epidemiology programs. Major components of the NCI Ireland Agreement will include some of the following: EDUCATION AND EXCHANGE OF SCHOLARS: Education will form one of the major platforms of this agreement through the support of educational programs for medical, nursing and scientific staff. These will include the exchange of scholars, including Ph.D., M.D. and nursing students. Particular emphasis will be given to the exchange of medical and nursing trainees focused on clinical research. This will have an immediate clinical impact and will naturally extend the support that has already been given to the training of medical and scientific trainees from the Island of Ireland. Further exchanges would include Ph.D. students, laboratory-based M.D.s in training, clinical visiting professors and investigators from the U.S. wishing to extend their studies in Ireland. CLINICAL TRIALS: Another major area for partnership will be the enhancement of a clinical trials infrastructure and clinical trial development. Modernization of cancer care requires that delivery of care should be in the context of evidence-based medicine. This requires a vigorous and contemporary clinical trials infrastructure which would center around the clinical trials infrastructure already established at the Northern Ireland Cancer Centre and the Irish Clinical Oncology Research Group (ICORG) in the Republic of Ireland. The NCI has already commissioned the development of a new Clinical Trials Information System (CTIS) which seeks as its goal to set international standards in the clinical trials process, and it has already committed significant resources to its implementation. The outcome of this element of partnership will be that clinical trials performed in Irish institutions will immediately be compatible for collation, analysis and presentation with studies performed in the U.S. Moreover, this system will allow participating centers to immediately conform to international standards. This proposal therefore permits participating institutions in Northern Ireland and the Republic of Ireland to quickly achieve data management standards of the highest quality. TELECONFERENCING: Teleconferencing capabilities are already established in both the NCI and in Ireland and indeed limited teleconferencing linkages have already been established between the partners. Further investment in this infrastructure will be vital to the success of major elements of this partnership. It will facilitate clinical trial development, education programs, patient services development and exchange of clinical and scientific ideas. Communication between sites will be essential to the success of this partnership. TUMOR REGISTRIES: Another area for major collaboration and partnership will be in the use of the Cancer Tumor Registries in both Northern Ireland and the Republic of Ireland. The monitoring of improvements in cancer care can only be undertaken with a reliable tumor registry that tracks population-based cancer incidence and mortality. These data are now available in both Northern Ireland and the Republic of Ireland, and both Governments recognize their importance. The NCI proposes to assist both Tumor Registries by developing a common database that can assist in consultation, informatic tools and quality control. Consolidation of the Registries, North and South, will improve the overall quality of data collection and provide information on a genetically stable population. This therefore will act as a major tool for epidemiological investigations and programs focused on screening and prevention. DEVELOPMENTS IN CANCER CLINICAL SERVICES: The NCI Ireland partnership also proposes to assist the further development of clinical service programs on the Island of Ireland. These will include the improvement and standardization of Radiation Oncology practice and the development of a consolidated Radiation Oncology program for research. There are a limited number of radiation facilities on the Island of Ireland and there are significant needs in terms of linking practice elements and the implementation of uniform standards of practice. Assistance in standardizing and driving the development of clinical services will also extend to elements of medical and surgical oncology practice as well as palliative care. The development of palliative care services is already at an advanced stage on the Island of Ireland and is one that the NCI will carefully evaluate in terms of its own developing programs. THE NCI ALL IRELAND CANCER CONFERENCE: An important event to highlight the commencement of this special relationship will be the NCI All Ireland Cancer Conference to be held in Belfast October 3-6, 1999. This Conference will address clinical, laboratory, epidemiological and political issues that are pertinent to the care of cancer patients. It will highlight important work by Irish, American and European scientists with further input from well-known international academic and biotechnology investigators from across the world. These international experts will not only be asked to speak on their areas of expertise but also to comment on clinical and scientific programs that may help improve North and South interaction and Transatlantic collaboration. Finally, it is hoped that the Conference will be a marker of a very special interaction on the Island of Ireland focused on the overall development of cancer services for patients. It will also signal the start of an important partnership between the NCI and those involved in cancer care and research in Ireland. This tripartite cooperative agreement is a most exciting venture and it will hopefully be an example of how an effort focused on a human problem common to all societies can generate a spirit of cooperation and help to eliminate strife.

Journal Article↗

PubMed1994

Relation between physical growth and information processing in infants born in India.

The relation between physical growth and cognitive development in infants growing up in India was examined in this study. Subjects were 183 5-12-month-olds. Weight and length, two anthropometric measures commonly used to index nutritional status in developing countries, related to infant measures of visual recognition memory and tactual-visual cross-modal transfer. Underweight infants performed relatively poorly on both cognitive measures and failed to show the clear age-related improvements in speed of processing found among the heavier infants. Weight and length correlated with both measures of infant cognition, r = .25 to r = .45, as did, to a lesser degree, head circumference. Although birthweight, previous illness, and parental education were also related to development, the relations between infant growth and cognition remained significant even after these variables were statistically controlled.

Anthropometry↗

PubMed2006

On the dynamics of molecular conformation.

Understanding the mechanism of fast transitions between conformed states of large biomolecules is central to reconciling the dichotomy between the relatively high speed of metabolic processes and slow (random-walk based) estimates on the speed of biomolecular processes. Here we use the dynamical systems approach to suggest that the reduced time of transition between different conformations is due to features of the dynamics of molecules that are a consequence of their structural features. Long-range and local effects both play a role. Long-range molecular forces account for the robustness of final states and nonlinear processes that channel localized, bounded disturbances into collective, modal motions. Local interconnections provide fast transition dynamics. These properties are shared by a class of networked systems with strong local interconnections and long-range nonlinear forces that thus exhibit flexibility and robustness at the same time.

Macromolecular Substances↗

PubMed1997

Sequential and coordinative complexity in time-accuracy functions for mental arithmetic.

Time-accuracy functions for tasks involving single-digit mental addition and subtraction were derived in a sample of 18 younger (mean age = 21.7 years) and 16 older adults (mean age = 68.8 years). Sequential complexity was manipulated by varying the number of operations (5 vs. 10); coordinative complexity was induced by bracketing. Age differences were apparent in the coordinative conditions, even though no age difference was present in the sequential conditions. This indicates that the age difference under conditions of high coordinative demands could not be attributed solely to a decline in basic speed of processing. The Age x Complexity interaction was due to larger onset times and lower asymptotic performance by the older adults in the coordinative conditions but not due to to rate of approach to the asymptote. This implies that coordinative demands do not differentially hurt access from semantic memory in older adults; however, coordinative demands do have disproportionately negative consequences for computation speed and self-monitoring in older adults.

Adult↗

PubMed2003

RecBCD enzyme is a bipolar DNA helicase.

Escherichia coli RecBCD is a heterotrimeric helicase/nuclease that catalyses a complex reaction in which double-strand breaks in DNA are processed for repair by homologous recombination. For some time it has been clear that the RecB subunit possesses a 3' --> 5' DNA helicase activity, which was thought to drive DNA translocation and unwinding in the RecBCD holoenzyme. Here we show that purified RecD protein is also a DNA helicase, but one that possesses a 5' --> 3' polarity. We also show that the RecB and RecD helicases are both active in intact RecBCD, because the enzyme remains capable of processive DNA unwinding when either of these subunits is inactivated by mutation. These findings point to a bipolar translocation model for RecBCD in which the two DNA helicases are complementary, travelling with opposite polarities, but in the same direction, on each strand of the antiparallel DNA duplex. This bipolar motor organization helps to explain various biochemical properties of RecBCD, notably its exceptionally high speed and processivity, and offers a mechanistic insight into aspects of RecBCD function.

Adenosine Triphosphatases↗

PubMed2003

Event-related potentials to Stroop and reverse Stroop stimuli.

In the Stroop task, the latency of response to a colour is either faster or slower in the presence of a congruent or incongruent colour-word (J. Exp. Psychol. 18 (1935) 643). Debate remains as to whether this effect occurs during early stimulus processing or late response competition. The present study examined the task using reaction time (RT) and event-related potentials to determine temporal differences in this processing. The 'reverse Stroop' effect (where colour interferes with processing of a colour-word) which is much less well established, was also examined. Standard Stroop interference was found as well as reverse Stroop interference. A late lateralised negativity at frontal sites was greater for Incongruent trials and also for the word-response (reverse Stroop) task, and was interpreted as semantic selection and word-rechecking effects. Late positive component latency effects generally mirrored the speed of processing of the different conditions found in RT data. Stroop effects were also found in early temporal N100 and parietal P100 components, which differentiated Congruent from Incongruent trials in the reverse Stroop but not the standard Stroop, and were interpreted as early perception of physical mismatch between the colour and word. It was concluded that Stroop stimuli are processed in parallel in a network of brain areas rather than a particular structure and that Stroop interference arises at the output stage.

Adult↗

PubMed1999

Selective effects of nicotine on attentional processes.

RATIONALE: It is now well established from electrophysiological and behavioural evidence that nicotine has effects on information processing. The results are usually explained either by a primary effect of nicotine or by a reversal effect of a nicotine-induced, abstinence deficit. In addition, there is dispute about the cognitive processes underlying the changes in performance. METHODS: This study has approached the first question by using the nicotine patch, in order to administer nicotine chronically. In addition, we examined the effects of nicotine on attention with a selection of tests which assessed the intensity and selectivity features of attention, using the Random Letter Generation test, the Flexibility of Attention test and the Stroop test. RESULTS: Nicotine enhanced the speed of number generation and the speed of processing in both the control and interference conditions of the Stroop test. There were no effects on attentional switching of the Flexibility of Attention test. CONCLUSION: The results are consistent with the hypothesis that nicotine mainly improves the intensity feature of attention, rather than the selectivity feature.

Adolescent↗

PubMed2005

Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity.

On-line Raman spectroscopy was used to evaluate the effect of blending time on low dose, 1%, blend uniformity of azimilide dihydrochloride. An 8 qt blender was used for the experiments and instrumented with a Raman probe through the I-bar port. The blender was slowed to 6.75 rpm to better illustrate the blending process (normal speed is 25 rpm). Uniformity was reached after 20 min of blending at 6.75 rpm (135 revolutions or 5.4 min at 25 rpm). On-line Raman analysis of blend uniformity provided more benefits than traditional thief sampling and off-line analysis. On-line Raman spectroscopy enabled generating data rich blend profiles, due to the ability to collect a large number of samples during the blending process (sampling every 20s). In addition, the Raman blend profile was rapidly generated, compared to the lengthy time to complete a blend profile with thief sampling and off-line analysis. The on-line Raman blend uniformity results were also significantly correlated (p-value < 0.05) to the HPLC uniformity results of thief samples.

Chemistry, Pharmaceutical↗

PubMed2004

Quality, not quantity: the role of natural products and chemical proteomics in modern drug discovery.

Chemical genetics and reverse chemical genetics parallel classical genetics but target genes at the protein level and have proven useful in recent years for screening combinatorial libraries for compounds of biological interest. However, the performance of combinatorial chemistry in filling pharmaceutical pipelines has been lower than anticipated and the tide may be turning back to Nature in the search for new drug candidates. Even though diversity oriented synthesis is now producing molecules that are natural product-like in terms of size and complexity, these molecules have not evolved to interact with biomolecules. Natural products, on the other hand, have evolved to interact with biomolecules, which is why so many can be found in pharmacopoeias. However, the cellular targets and modes of action of these fascinating compounds are seldom known, hindering the drug development process. This review focuses on the emergence of chemical proteomics and reverse chemical proteomics as tools for the discovery of cellular receptors for natural products, thereby generating protein/ligand pairs that will prove useful in identifying new drug targets and new biologically active small molecule scaffolds. Such a system-wide approach to identifying new drugable targets and their small molecule ligands will help unblock the pharmaceutical product pipelines by speeding the process of target and lead identification.

Animals↗

PubMed1996

Ca2+ dependence of dark- and light-adapted flash responses in rod photoreceptors.

Light adaptation is thought to be orchestrated by a Ca2+ feedback signal that desensitizes the response by speeding recovery. To evaluate the role of Ca2+ in adaptation, we compared the effect of lowered Ca2+ on response properties in darkness and during adaptation. Internal Ca2+ was reduced from its normal resting dark level (535 nM) by either background illumination or exposure to Ringer's solution containing low Ca2+ and/or cyclic GMP-gated channel blockers in darkness. Ca2+ reductions in light decreased the activation gain of the transduction process and speeded recovery kinetics, while equivalent Ca2+ reductions in darkness caused similar gain reduction without accelerating recovery. This indicates that adaptational changes in the response are not due purely to feedback effects on recovery.

Adaptation, Ocular↗

PubMed2001

Thalamic volume predicts performance on tests of cognitive speed and decreases in healthy aging. A magnetic resonance imaging-based volumetric analysis.

Recent studies have indicated a role for the thalamus in attention, arousal and the capacity to perform tasks of speeded information processing. The present study evaluated the role of the thalamus in age-related cognitive decline by investigating the correlations between thalamic volume, cognition and age. This was done in 57 healthy subjects ranging from 21 to 82 years of age. All subjects underwent neurocognitive testing with information processing tests and structural magnetic resonance imaging. A significant decrease in volume of the thalamus with increasing age was found, relatively stronger than and independent of the decrease of total brain volume. The decrease of thalamic volume was apparent before the onset of loss of volume of the total brain. Over the age-span studied, the thalamic decrease in volume correlated with the diminished performance on tests of cognitive speed. Additionally, in young and middle-aged, but not in old subjects, the size of the thalamus predicted performance on tasks that require cognitive speed.

Adult↗

PubMed1999

One voice too many: adult age differences in language processing with different types of distracting sounds.

An experiment is reported that investigated factors that might contribute to age differences in the ability to process spoken language under conditions of competition from various types of background noise. Age differences in recall of spoken sentences were shown to depend on the type of background noise as well as its intensity. Increased intensity levels of just one competing speaker produced differentially greater impairment in older adults than in young adults. Analyses showed that listening performance was predicted not only by individual differences in hearing ability but also by speed of processing, which underscores the combined role of age-related auditory and cognitive changes in processing spoken language.

Adolescent↗