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PubMed1992

Hospitalization experiences in the long-term care trajectories of a Medicaid cohort.

Two groups of applicants (859 screened in the community and 607 screened in acute care) for Medicaid-reimbursed long-term care were followed for 1 year from their initial long-term care assessments. The role hospitalizations play in long-term care trajectories was explored. Results reinforce the need for active partnerships between acute care and long-term care multidisciplinary teams for ongoing management of a large number of Medicaid clients and their families.

Demography↗
PubMed1997

Developmental trajectory and disease progression in schizophrenia: the conundrum, and insights from a 12-year prospective study in the Monaghan 101.

Though conceptualised originally as a deteriorating disorder, some contemporary studies have been interpreted as challenging these foundations; more radically, it has been proposed that schizophrenia may be a 'static encephalopathy' of neurodevelopmental origin. The argument offered here is that schizophrenia is indeed a neurodevelopmental disorder, but that this is not in itself antithetical to later disease progression. Rather, the onset of psychosis may reflect the maturationally-mediated triggering of an active disease process that is associated with progressive deterioration unless attenuated by antipsychotic drugs. A developmental trajectory is proposed to link first or early second trimester dysplasia to the chronic course of the illness; from this, it is argued that schizophrenia is inherently a progressive disorder but that antipsychotic drugs may act to ameliorate this progressive component and thus confer on the disease course some of the characteristics of a 'static encephalopathy'. The 'true' natural history of an illness cannot be determined from studies in treated populations.

Antipsychotic Agents↗
PubMed2001

Vulnerability to involuntary movements over a lifetime trajectory of schizophrenia approaches 100%, in association with executive (frontal) dysfunction.

This study assessed the prevalence of involuntary movements among older inpatients with severe schizophrenia, many of whom had experienced a lifetime of illness and its treatment, and examined their neuropsychological correlates. The subjects of this study were 128 inpatients with a DSM-IV diagnosis of schizophrenia. They were assessed using the Abnormal Involuntary Movement Scale, the Mini-Mental State Examination for general cognitive impairment and the Executive Interview for executive dyscontrol; additionally, their medical records were reviewed in detail for treatment histories. Prevalence of involuntary movements was examined and their clinical correlates determined in relation to topography of movement disorder using logistic regression. In schizophrenia, prevalence of involuntary movements was: age <65years, 63%; 65-75years, 80%; >75years, 93%. The primary correlate both of overall and of orofacial movements was poor executive function, whereas the primary correlate of limb-trunkal movements was poor general cognitive function. On approaching the limits of human longevity following a lifetime trajectory of illness and its treatment, essentially 'all' patients with schizophrenia appear inherently vulnerable to the emergence of involuntary movements in topographically specific association with cognitive deficits.

Adult↗
PubMed1999

Internal models for motor control and trajectory planning.

A number of internal model concepts are now widespread in neuroscience and cognitive science. These concepts are supported by behavioral, neurophysiological, and imaging data; furthermore, these models have had their structures and functions revealed by such data. In particular, a specific theory on inverse dynamics model learning is directly supported by unit recordings from cerebellar Purkinje cells. Multiple paired forward inverse models describing how diverse objects and environments can be controlled and learned separately have recently been proposed. The 'minimum variance model' is another major recent advance in the computational theory of motor control. This model integrates two furiously disputed approaches on trajectory planning, strongly suggesting that both kinematic and dynamic internal models are utilized in movement planning and control.

Animals↗
PubMed2002

Normalized fifth-order spherical aberration coefficients derived from a Gaussian trajectory on rotationally symmetrical magnetic lenses.

This paper reports normalized fifth-order spherical aberration coefficients C(5s)/R derived from Gaussian trajectory for rotationally symmetrical magnetic lenses, where S/D (the polepiece gap-width/bore-diameter ratio) is in the range 0.20-2.00, and k(2) (the lens-intensity parameter) is 0.10-100. It is noted that the normalized fifth-order spherical-aberration coefficient C(5s)/R changes its sign within the given parameter ranges.

Journal Article↗
PubMed1996

Effects of endothelin-1 on [Ca2+]i-shortening trajectory and Ca2+ sensitivity in rabbit single ventricular cardiomyocytes loaded with indo-1/AM: comparison with the effects of phenylephrine and angiotensin II.

In most mammalian species, activation of myocardial endothelin as well as alpha1-adrenergic and angiotensin receptors leads to an increase in contractile function and myocardial cell hypertrophy, in association with acceleration of PI hydrolysis and with resultant production of IP3 and diacylglycerol. Therefore, these receptors may share a common intracellular signal transduction process in cardiac regulation. Although the pathophysiological relevance of endothelin- and angiotensin-mediated signal transduction has been postulated to play a key role in the progress of congestive heart failure, the details of the regulation are still controversial. We carried out experiments to further study the regulation induced by activation of these receptors. In spite of a wide range of species-dependent variation among mammals in the induction of the cardiotonic effect via these receptors, there is an excellent correlation between the extent of acceleration of PI hydrolysis and the positive inotropic effect (associated with a negative lusitropic effect) of the respective receptor agonists under most experimental conditions in rabbit ventricular myocardium. In isolated rabbit ventricular cardiomyocytes loaded with indo-1/AM, activation of these receptors elicited a very similar changes in the relationship between [Ca2+]i and cell shortening: the [Ca2+]i-shortening trajectory was shifted mainly upwards and the relationship of peak shortening vs peak [Ca2+]i was shifted to the left, an indication that the PIE of these agonists is consistently associated with an increase in [Ca2+]i and in the sensitivity of myofilaments to Ca2+ ions under the same experimental condition. Pieces of evidence in biochemical and pharmacological analyses imply that the products of PI hydrolysis, namely diacylglycerol and subsequent activation of protein kinase C, might play a crucial role in the regulation of cardiac function that is induced upon activation of endothelin, angiotensin and alpha-adrenergic receptors in the rabbit ventricular myocardium.

Angiotensin II↗
PubMed2002

Chronic hypoxia alters the physiological and morphological trajectories of developing chicken embryos.

Chicken embryos were chronically exposed to hypoxia (P(O(2)) approximately 110 mmHg) during development, and assessed for detrimental metabolic and morphological effects. Eggs were incubated in one of four groups: control (i.e. 151 mmHg), or treated with continuous 110 mmHg (15% O(2)) during days 1-6 (H1-6), 6-12 (H6-12), or 12-18 (H12-18) with normoxia during the remaining incubation. Metabolism (V(O(2))), body mass, hemoglobin (Hb) and hematocrit (Hct) were measured in embryos on days 12 and 18 of incubation and in day-old hatchlings. Ability to maintain V(O(2)) was acutely measured during a step-wise decrease in P(O(2)) from normoxia to hypoxia (55 mmHg). On day 12, V(O(2)) of H1-6 eggs were significantly lower than in the control and H6-12 eggs. P(crit) in H6-12 eggs was lower than in control and H1-6 eggs. Body mass of H1-6 and H6-12 embryos on day 12 was significantly lower than in control embryos, while in H6-12 embryos, Hct and Hb were higher. On day 18, H6-12 embryos had significantly lower V(O(2)) than control eggs. Body mass of H6-12 and H12-18 embryos was significantly lower than control embryos. Hct and Hb did not differ between treatments. In hatchlings, mass, Hb and Hct had returned to values statistically identical to controls. However, H6-12 embryos had significantly lower V(O(2)). Long-term hypoxia altered V(O(2)) when hypoxic incubation occurred during the middle third of incubation, but not during earlier or later incubation. Thus, chronic hypoxic exposure during critical periods in development altered the developmental physiological trajectories and modified the phenotypes of the developing embryos.

Animals↗
PubMed2003

Evaluation of trajectories and contact pressures for the straight nucleus cochlear implant electrode array - a two-dimensional application of finite element analysis.

A two-dimensional (2D) finite element analysis has been used in this study to model the insertion of the Nucleus electrode array with different stiffness properties in order to evaluate the propensity of damage by visualizing the predicted trajectories and by comparing the buckling stresses and the contact pressures at the tip (and its distribution along the length) of the electrode array. Previous temporal bone studies have shown that damage during insertion of an electrode array around the basal turn of the cochlear spiral could be related to the design and the stiffness properties of the electrode array. However, it is difficult to evaluate different designs of electrode arrays purely by experimental methods as the experimental conditions and their results are difficult to reproduce. Three electrode arrays with different mechanical properties, i.e. uniform stiffness, graded stiffness, and a soft tip have been modelled. Buckling stress and contact pressure at the tip of the electrode array were found to be highest for the arrays with uniform stiffness. The contact pressures at the tip of the electrode array appeared strongly influenced by the stiffness profile and were optimal for graded stiffness. The results indicate the importance of the electrode array design and stiffness properties in minimizing trauma. However, there are a number of limitations in the present 2D evaluation which will require further analysis using a three-dimensional model to obtain definitive results.

Cochlea↗
PubMed2002

Atypical trajectories of number development: a neuroconstructivist perspective.

Despite the fact that number deficits are as prevalent as literacy deficits, research on basic numerical skills lags seriously behind the successful studies identifying low-level deficits in dyslexia. We review current debates on number, discussing how the competing theories pertain to mathematical disabilities in normal children and numeracy deficits in genetic disorders. We stress the need to consider these issues within the framework of a developing system rather than from the neuropsychological perspective of focal damage. The earlier the exploration of atypical trajectories in very basic numerical skills, the better we will be able to chart their developmental impact on subsequent, higher-level arithmetic abilities.

Journal Article↗
PubMed2002

The interactive effects of infant activity level and fear on growth trajectories of early childhood behavior problems.

The current study examined the interactive effects of infant activity level and fear on growth trajectories of behavior problems in early childhood (age 4 to 8 years) using maternal ratings. The sample was drawn from the National Longitudinal Survey of Youth (NLSY) and included children who were between 1 and 11 months in 1986. Findings suggested that boys characterized by high activity level and low levels of fear in infancy escalated in both externalizing and internalizing symptoms. Also, boys characterized by high fear and low activity level increased in internalizing symptoms and these effects seemed to be specific to depression rather than anxiety. Temperament did not predict escalation in externalizing symptomatology for girls, but low levels of fear predicted increases in internalizing symptoms. There was also evidence for a decline in depression specific symptoms for girls characterized by high fear and low activity in infancy. These findings suggest the importance of examining interactive models of temperament risk and considering gender specific pathways to behavior problems.

Age Factors↗
PubMed2004

Early adolescent through young adult alcohol and marijuana use trajectories: early predictors, young adult outcomes, and predictive utility.

The present study takes a developmental approach to subgrouping and examines the trajectories of substance use from early adolescence through young adulthood among a community sample of 481 individuals. The patterns of use were examined, subgroups were identified separately for men and women and for alcohol and marijuana, and psychosocial predictors and psychopathology outcomes that differentiated the groups were identified. The results revealed three substantially overlapping subgroups for both alcohol and marijuana: early onset, late onset, and nonuser. Although the general patterns of which dependent variables were related to group were similar for alcohol and marijuana, a closer examination revealed important subgroup differences. For alcohol use, the early-onset group was more dysfunctional in terms of predictors and outcomes whereas the late-onset and nonuser groups were better adjusted. In contrast, for marijuana, the early- and late-onset groups were both more dysfunctional than the nonuser group. In a final analysis, we examined the predictive utility of our developmental approach to subgrouping compared to a traditional, static approach.

Adolescent↗
PubMed2006

Developmental trajectories of externalizing and internalizing behaviors: factors underlying resilience in physically abused children.

Using a multisite community sample of 585 children, this study examined how protective and vulnerability factors alter trajectories of teacher-reported externalizing and internalizing behavior from kindergarten through Grade 8 for children who were and were not physically abused during the first 5 years of life. Early lifetime history of physical abuse (11.8% of sample) was determined through interviews with mothers during the prekindergarten period; mothers and children provided data on vulnerability and protective factors. Regardless of whether the child was abused, being African American; being male; having low early social competence, low early socioeconomic status (SES), and low adolescent SES; and experiencing adolescent harsh discipline, low monitoring, and low parental knowledge were related to higher levels of externalizing problems over time. Having low early social competence, low early SES, low adolescent SES, and low proactive parenting were related to higher levels of internalizing problems over time. Furthermore, resilience effects, defined as significant interaction effects, were found for unilateral parental decision making (lower levels are protective of externalizing outcomes for abused children), early stress (lower levels are protective of internalizing outcomes for abused children), adolescent stress (lower levels are protective of internalizing outcomes for abused children), and hostile attributions (higher levels are protective of internalizing outcomes for abused children). The findings provide a great deal of support for an additive or main effect perspective on vulnerability and protective factors and some support for an interactive perspective. It appears that some protective and vulnerability factors do not have stronger effects for physically abused children, but instead are equally beneficial or harmful to children regardless of their abuse status.

Adolescent↗
PubMedDate not supplied

Trajectories of psychosis: towards a new social biology of schizophrenia.

Over the last 2 decades, discourse on the causes of schizophrenia was conducted almost entirely in terms of biological risk factors. This was probably the result of social trends in the research community, and in popular culture, as a wave of techno-optimism promised answers to big human questions in terms of small pixels and even smaller molecules. The human genome project inflated expectations further, and the pharmaceutical industry conspired with the desire of psychiatrists for scientific respectability. 'Social factors', whether at macro-societal or locality/family level, came to be seen as 'fall-out' from biological mechanisms, a kind of padding to our understanding of human disease. But changes are in the wind. New understandings of the influence of social factors on the long-term outcome trajectories of psychosis, their potential role in risks associated with migration, and recent findings from genetic high risk studies, are raising fresh questions about social factors and causation. This paper does not argue that the evidence (yet) is strong. But after 2 decades of often crudely articulated dualism, it is time once again for social experience to be integrated with more sophisticated theory development and hypothesis testing in the search for the causes of schizophrenia.

Humans↗
PubMedDate not supplied

Cellular trajectories of peptide-modified gold particle complexes: comparison of nuclear localization signals and peptide transduction domains.

Gold nanoparticles modified with nuclear localization peptides were synthesized and evaluated for their subcellular distribution in HeLa human cervical epithelium cells, 3T3/NIH murine fibroblastoma cells, and HepG2 human hepatocarcinoma cells. Video-enhanced color differential interference contrast microscopy and transmission electron microscopy indicated that transport of nanoparticles into the cytoplasm and nucleus depends on peptide sequence and cell line. Recently, the ability of certain peptides, called protein transduction domains (PTDs), to transclocate cell and nuclear membranes in a receptor- and temperature-independent manner has been questioned (see for example, Lundberg, M.; Wikstrom, S.; Johansson, M. (2003) Mol. Ther. 8, 143-150). We have evaluated the cellular trajectory of gold nanoparticles carrying the PTD from HIV Tat protein. Our observations were that (1) the conjugates did not enter the nucleus of 3T3/NIH or HepG2 cells, and (2) cellular uptake of Tat PTD peptide-gold nanoparticle conjugates was temperature dependent, suggesting an endosomal pathway of uptake. Gold nanoparticles modified with the adenovirus nuclear localization signal and the integrin binding domain also entered cells via an energy-dependent mechanism, but in contrast to the Tat PTD, these signals triggered nuclear uptake of nanoparticles in HeLa and HepG2 cell lines.

3T3 Cells↗
PubMed2002

Evolution of nitrogen species air pollutants along trajectories crossing the Los Angeles area.

Ambient aerosol sampling was conducted in Diamond Bar, Mira Loma, and Riverside, CA, to observe at close range the effects of ammonia emissions on air quality. These sites are located upwind,within, and downwind, respectively, of the Chino dairy area, the largest single source of ammonia emissions in the Los Angeles area. Inertial impactors and bulk filter samplers provided 4-7-h measurements of aerosol chemical composition and size distribution. Daily average fine particle mass concentrations were in the range 22.4-143.0 microg m(-3). On some days the fine particulate matter concentrations were more than two times greater than the proposed 24-h Federal standard of 65 microg m(-3). Ammonium nitrate was the largest component of fine particle mass at all three sites; 24-h average fine particulate ammonium plus nitrate concentrations ranged from 11.7 to 75.4 microg m(-3). A single air mass was studied as it passed the Diamond Bar air monitoring site in the morning and stagnated near Mira Loma in the evening of the same day. Between these two sites NO was oxidized to NO2, and the ammonia concentration increased by a factor of 5. A second air parcel trajectory, which stagnated near Mira Loma during the early morning and passed near the Riverside site approximately 24 h later, showed a decrease in ammonia concentration over time that is consistent with dilution as the air mass moved downwind from the source of ammonia in the dairy area. Particulate NH4NO3 concentration in that air parcel remained approximately constant over time, consistent with a continued excess of NH3 relative to HNO3 downwind of the dairy area.

Air Pollutants↗
PubMed2001

A single transition state serves two mechanisms: an ab initio classical trajectory study of the electron transfer and substitution mechanisms in reactions of ketyl radical anions with alkyl halides.

Molecular dynamics has been used to investigate the reaction of a series of ketyl anion radicals and alkyl halides, CH2O(*)(-) + CH3X (X = F, Cl, Br) and NCCHO(*)(-) + CH3Cl. In addition to a floppy outer-sphere transition state which leads directly to ET products, there is a strongly bound transition state that yields both electron transfer (ET) and C-alkylated (SUB(C)) products. This common transition state has significant C-- C bonding and gives ET and SUB(C) products via a bifurcation on a single potential energy surface. Branching ratios have been estimated from ab initio classical trajectory calculations. The SUB(C) products are favored for transition states with short C--C bonds and ET for long C--C bonds. ET reactivity can be observed even at short distances of r(C)(-)(C) = ca. 2.4 A as in the transition state for the reaction NCCHO(*)(-) + CH3Cl. Therefore, the ET/SUB(C) reactivity is entangled over a significant range of the C--C distance. The mechanistic significance of the molecular dynamics study is discussed.

Journal Article↗
PubMed2002

Nonstatistical dynamics in deep potential wells: a quasiclassical trajectory study of methyl loss from the acetone radical cation.

The loss of methyl radical from the acetone radical cation, following its formation from the enol isomer, has been found to be nonergodic. The origins of this behavior are probed computationally by a quasiclassical trajectory simulation on an AM1-SRP potential energy surface. Experimental reaction outcomes are qualitatively reproduced, and evidence is presented that coherent excitation of the CCO angle bending during isomerization is a significant factor in the nonstatistical behavior.

Journal Article↗