Nonlinear Elasticity in Biological Gels

Unlike most synthetic materials, biological materials often stiffen as they are deformed. This nonlinear elastic response, critical for the physiological function of some tissues, has been documented since at least the 19th century, but the molecular structure and the design principles responsible for it are unknown. Current models for this response require geometrically complex ordered structures unique to each material. In this Article we show that a much simpler molecular theory accounts for strain stiffening in a wide range of molecularly distinct biopolymer gels formed from purified cytoskeletal and extracellular proteins. This theory shows that systems of semi-flexible chains such as filamentous proteins arranged in an open crosslinked meshwork invariably stiffen at low strains without the need for a specific architecture or multiple elements with different intrinsic stiffnesses.Comment: 23 pages, 5 figures, submitted to Natur

Distributed model predictive control of linear systems with persistent disturbances

This article presents a new form of robust distributed model predictive control (MPC) for multiple dynamically decoupled subsystems, in which distributed control agents exchange plans to achieve satisfaction of coupling constraints. The new method offers greater flexibility in communications than existing robust methods, and relaxes restrictions on the order in which distributed computations are performed. The local controllers use the concept of tube MPC – in which an optimisation designs a tube for the system to follow rather than a trajectory – to achieve robust feasibility and stability despite the presence of persistent, bounded disturbances. A methodical exploration of the trades between performance and communication is provided by numerical simulations of an example scenario. It is shown that at low levels of inter-agent communication, distributed MPC can obtain a lower closed-loop cost than that obtained by a centralised implementation. A further example shows that the flexibility in communications means the new algorithm has a relatively low susceptibility to the adverse effects of delays in computation and communication

Formative peer assessment in a CSCL environment

In this case study our aim was to gain more insight in the possibilities of qualitative formative peer assessment in a computer supported collaborative learning (CSCL) environment. An approach was chosen in which peer assessment was operationalised in assessment assignments and assessment tools that were embedded in the course material. The course concerned a higher education case-based virtual seminar, in which students were asked to conduct research and write a report in small multidisciplinary teams. The assessment assignments contained the discussion of assessment criteria, the assessment of a group report of a fellow group, and writing an assessment report. A list of feedback rules was one of the assessment tools. A qualitative oriented study was conducted, focussing on the attitude of students towards peer assessment and practical use of peer assessment assignments and tools. Results showed that students’ attitude towards peer assessment was positive and that assessment assignments had added value. However, not all students fulfilled all assessment assignments. Recommendations for implementation of peer assessment in CSCL environments as well as suggestions for future research are discussed

The Neuroscience Information Framework: A Data and Knowledge Environment for Neuroscience

With support from the Institutes and Centers forming the NIH Blueprint for Neuroscience Research, we have designed and implemented a new initiative for integrating access to and use of Web-based neuroscience resources: the Neuroscience Information Framework. The Framework arises from the expressed need of the neuroscience community for neuroinformatic tools and resources to aid scientific inquiry, builds upon prior development of neuroinformatics by the Human Brain Project and others, and directly derives from the Society for Neuroscience’s Neuroscience Database Gateway. Partnered with the Society, its Neuroinformatics Committee, and volunteer consultant-collaborators, our multi-site consortium has developed: (1) a comprehensive, dynamic, inventory of Web-accessible neuroscience resources, (2) an extended and integrated terminology describing resources and contents, and (3) a framework accepting and aiding concept-based queries. Evolving instantiations of the Framework may be viewed at http://nif.nih.gov, http://neurogateway.org, and other sites as they come on line

Association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth.

OBJECTIVE: To determine the association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth. DESIGN: Multicentre prospective cohort study. SETTING: Ten European centres offering prenatal screening for toxoplasmosis. POPULATION: Deliveries after 23 weeks of gestation in 386 women with singleton pregnancies who seroconverted to toxoplasma infection before 20 weeks of gestation. Deliveries after 36 weeks in 234 women who seroconverted at 20 weeks or later, and tested positive before 37 weeks. METHODS: Comparison of infected and uninfected births, adjusted for parity and country of birth. MAIN OUTCOME MEASURES: Differences in gestational age at birth, birthweight and birthweight centile. RESULTS: Infected babies were born or delivered earlier than uninfected babies: the mean difference for seroconverters before 20 weeks was -5.4 days (95% CI: -1.4, -9.4), and at 20 weeks or more, -2.6 days (95% CI: -0.5, -4.7). Congenital infection was associated with an increased risk of preterm delivery when seroconversion occurred before 20 weeks (OR 4.71; 95% CI: 2.03, 10.9). No significant differences were detected for birthweight or birthweight centile. CONCLUSION: Babies with congenital toxoplasmosis were born earlier than uninfected babies but the mechanism leading to shorter length of gestation is unknown. Congenital infection could precipitate early delivery or prompt caesarean section or induction of delivery. We found no evidence for a significant association between congenital toxoplasmosis and reduced birthweight or small for gestational age birth

Late widespread skeletal metastases from myxoid liposarcoma detected by MRI only

Background Myxoid liposarcoma is the second most commonly occurring sub-type of liposarcomas. In contrast to other soft tissue sarcomas, it is known to have a tendency to spread toward extrapulmonary sites, such as soft tissues, retroperitoneum, and the peritoneal surface. Bony spread, however, is not as common. Case presentation We report an unusual case of diffuse skeletal metastases from myxoid liposarcoma occurring 13 years after treatment of the primary tumour in the left lower limb. The skeletal spread of the disease was demonstrated on MRI only after other imaging modalities (plain radiography, CT and TC99 bone scans) had failed to detect these metastases. Conclusion MRI is an extremely sensitive and specific screening tool in the detection of skeletal involvement in these types of sarcomas, and therefore, should be a part of the staging proces

Withdrawing intra-aortic balloon pump support paradoxically improves microvascular flow

Introduction: The Intra-Aortic Balloon Pump (IABP) is frequently used to mechanically support the heart. There is evidence that IABP improves microvascular flow during cardiogenic shock but its influence on the human microcirculation in patients deemed ready for discontinuing IABP support has not yet been studied. Therefore we used sidestream dark field imaging (SDF) to test our hypothesis that human microcirculation remains unaltered with or without IABP support in patients clinically ready for discontinuation of mechanical support. Methods: We studied 15 ICU patients on IABP therapy. Measurements were performed after the clinical decision was made to remove the balloon catheter. We recorded global hemodynamic parameters and performed venous oximetry during maximal IABP support (1:1) and 10 minutes after temporarily stopping the IABP therapy. At both time points, we also recorded video clips of the sublingual microcirculation. From these we determined indices of microvascular perfusion including perfused vessel density (PVD) and microvascular flow index (MFI). Results: Ceasing IABP support lowered mean arterial pressure (74 +/- 8 to 71 +/- 10 mmHg; P = 0.048) and increased diastolic pressure (43 +/- 10 to 53 +/- 9 mmHg; P = 0.0002). However, at the level of the microcirculation we found an increase of PVD of small vessels <20 mu m (5.47 +/- 1.76 to 6.63 +/- 1.90; P = 0.0039). PVD for vessels >20 mu m and MFI for both small and large vessels were unaltered. During the procedure global oxygenation parameters (ScvO(2)/SvO(2)) remained unchanged. Conclusions: In patients deemed ready for discontinuing IABP support according to current practice, SDF imaging showed an increase of microcirculatory flow of small vessels after ceasing IABP therapy. This observation may indicate that IABP impairs microvascular perfusion in recovered patients, although this warrants confirmatio

Narcissistic personality disorder: Relations with distress and functional impairment

Abstract This study examined the construct validity of Narcissistic Personality Disorder (NPD) by examining the relations between NPD and measures of psychological distress and functional impairment both concurrently and prospectively across two samples. In particular, the goal was to address whether NPD typically &quot;meets&quot; Criterion C of the DSM-IV definition of Personality Disorder, which requires that the symptoms lead to clinically significant distress or impairment in functioning. Sample 1 (N =152) was composed of individuals receiving psychiatric treatment, while Sample 2 (N=151) was composed of both psychiatric patients (46%) and individuals from the community. NPD was linked to ratings of depression, anxiety, and several measures of impairment both concurrently and at 6-month follow-up. However, the relations between NPD and psychological distress were (a) small, especially in concurrent measurements, and (b) largely mediated by impaired functioning. NPD was most strongly related to causing pain and suffering to others, and this relationship was significant even when other Cluster B personality disorders were controlled. These findings suggest that NPD is a maladaptive personality style which primarily causes dysfunction and distress in interpersonal domains. The behavior of narcissistic individuals ultimately leads to problems and distress for the narcissistic individuals and for those with whom they interact. Narcissistic Personality Disorder: Relations with distress and functional impairment Narcissistic personality disorder (NPD), despite substantial interest from a theoretical perspective, has received very little empirical attention (1). In fact, some have concluded that &quot;most of the literature regarding patients suffering with narcissistic personality disorder is based on clinical experience and theoretical formulations, rather than empirical evidence&quot; (2; p. 303). A large majority of empirical studies on narcissism come from a social-personality psychology perspective which, while methodologically sophisticated and important, may not pertain to Narcissistic PD given the reliance on undergraduate samples and the use of the Narcissistic Personality Inventory (NPI, 3). Trull and McCrae (4) have noted that narcissism measured by the NPI appears to be made up of high Extraversion, low Agreeableness, and low Neuroticism from the Five-Factor Model of personality (5), while DSM definitions suggest low Agreeableness, high Neuroticism and no relation with Extraversion. These authors suggest that &quot;most narcissistic scales do not square well with DSM-III-R criteria for NAR&quot; (4; p.53). 1 Correspondence concerning this article can be addressed to Joshua D. Miller, Ph.D., Psychology Building, Department of Psychology, University of Georgia, Athens, GA 30602. Fax: (706) 542-8048 E-mail: [email protected]. Publisher&apos;s Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The field must be cautious about relying on these studies to inform our knowledge of NPD. The few empirical studies of NPD that have used clinical samples and DSM based measures have focused on the underlying factor structure and item content (6-8). In particular, there is a striking lack of data regarding the impairment and distress associated with NPD. Central to the issue of validity for any DSM disorder is whether it is actually associated with distress or impairment -in fact criterion C for PD from the DSM-IV (9, p. 689) mandates that one of the two be present in order to make a PD diagnosis. While there is good evidence for the functional impairment of PDs in general (10-11), and certain specific PDs such as borderline NIH Public Access As noted, the association between NPD and psychological distress is particularly unclear. The DSM-IV suggests that these individuals have a &quot;very fragile&quot; self-esteem (p. 714), are &quot;very sensitive to injury from criticism or defeat&quot; (p. 715), and that &quot;sustained feelings of shame or humiliation…may be associated with social withdrawal&quot; and &quot;depressed mood&quot; (p. 716). However, given the derivation of the DSM over time, these statements appear to be the result of expert opinion rather than empirical findings. Results from clinical samples are both sparse and contradictory. In fact, a meta-analysis of the relations between the FFM and DSM PDs found an effect size (i.e., r) of only .03 between Narcissism and Neuroticism, which measures emotional stability and the tendency to experience negative affective states such as depression, anxiety, and shame (14). However, this hides the substantial variability of the findings; of the 18 included effects, 5 were significantly positive, 7 were significantly negative, and 6 were nonsignificant. Within clinical samples, the effect size was .14 suggesting a small but significant relation to Neuroticism. There has also been some speculation that narcissism may be linked to higher rates of suicide Alternatively, Watson, Sawrie, Greene, and Arredondo (15) found significant negative relations between measures of narcissism (derived from the Minnesota Multiphasic Personality Inventory-2; 16) and depression in two clinical samples. Studies on comorbidity between PDs and Axis I disorders have not found a relation between NPD and depression or anxiety-related disorders Where the clinical lore and social-personality data do converge is on the interpersonal impairment linked with narcissism. The DSM-IV postulates that &quot;interpersonal relations are typically impaired due to problems derived from entitlement, the need for admiration, and the relative disregard for the sensitivities of others&quot; (p.716). Empirical studies of narcissism in the social-personality literature find that it predicts a self-centered, selfish and exploitative approach to interpersonal relationships, including game-playing, infidelity, a lack of empathy, and even violence (24-25). The negative consequences of narcissism are felt especially strongly by those who are involved with the narcissist (26). How quickly this personality style manifests this interpersonal impairment is up for debate. There is some evidence that the interpersonal difficulties associated with narcissism are only apparent over time, with narcissism being associated with apparently positive interpersonal functioning during initial relationship stages (27-28). However, other studies have found that individuals with unrealistically high positive self-evaluations are rated negatively by independent raters following a very brief competitive interaction with a peer (29). Unfortunately, there are very few data on NPD and interpersonal impairment using clinical samples. There are data from therapeutic relationships where items from a measure of countertransference were rated by a sample of psychiatrists and psychologists for patients with NPD. The authors of this study found that &quot;clinicians reported feeling anger, resentment, and dread in working with narcissistic personality disorder patients; feeling devalued and criticized by the patient; and finding themselves distracted, avoidant, and wishing to terminate the treatment&quot; (30, p. 894). These findings provide strong support for the interpersonal impairment these individuals experience as even trained clinicians experience strong negative feelings about these types of clients. Given the relatively stronger evidence of a link between NPD and interpersonal impairment than between NPD and psychological distress, it is plausible that NPD, at times, leads to clinically significant depression and/or anxiety but these negative affective states are probably secondary to the interpersonal impairment. That is, NPD may lead individuals to experience failure in a number of important domains (e.g., romance) that might lead to psychological distress; however, this distress may not be endemic to NPD. This may differ from other PDs such as borderline in which negative affectivity appears to be an intrinsic part of the disorder. The goals of the current study are to: 1. Assess the association between NPD and psychological distress including depression and anxiety. 2. Assess the association between NPD and impairment, including indices of romantic, social, occupational, and general impairment, as well as the spillover effects of NPD on significant others. 3. Assess the predictive power of NPD in relation to psychological distress and impairment over a 6-month period. 4. Test a model in which any positive link between narcissism and psychological distress is accounted for by impairment. 5. Assess the unique predictive power of NPD in predicting psychopathology and impairment, when controlling for the other Cluster B personality disorders. Method Participants and Procedures Sample 1-Participants (n = 152) were solicited from inpatient and outpatient programs at Western Psychiatric Institute and Clinic (WPIC) in Pittsburgh, PA. Patients with psychotic disorders, organic mental disorders, and mental retardation were excluded, as were patients with major medical illnesses that influence the central nervous system and might be associated with organic personality disturbance. Participants (in both samples) provided written informed consent after all study procedures had been explained. See Of the 152 individuals, 85 were women (56%), 135 were Caucasians (89%), 16 were African Americans (11%), and 1 was Asian American (1%), 121 were outpatients (80%), and the mean age was 34.5 years (SD = 9.4). Of the original sample, 105 (69%) were also assessed at a 6-month follow up. Attrition analyses were conducted on the following 16 variables: age, sex, race, treatment condition, marital status, education, and symptom counts for the 10 DSM III-R PDs that remain in the DSM-IV. No significant differences were found. Sample 2-This sample (n = 151) was comprised of 70 psychiatric patients and 81 nonpsychiatric participants. The non-psychiatric patients were recruited from two sources: diabetic patients (n = 23) or university faculty or staff (n = 58). This sample was part of a larger sample (n = 624) that was first screened for PDs. The larger sample was stratified on the basis of initial scores and individuals were randomly selected to participate in the interview portion of the study. The goal was to create a sample that had a 50% prevalence rate for PD. The psychiatric patients were solicited from an adult outpatient clinic at WPIC. The rule-outs used in Sample 1 were also utilized in this study. See Measures Consensus ratings of DSM-III-R (Sample 1) and DSM-IV (Sample 2) personality disorder criteria-Complete details of the assessment methodology are provided elsewhere (11,31). At intake, participants were interviewed for 6-10 hours in a minimum of 3 assessment sessions. The assessments sessions included structured symptom ratings, structured interviews for Axis I and Axis II disorders (e.g., the SCID, the PDE, SIDP-III-R, or SIDP-IV) and a detailed social and developmental history. Patients also completed self-report questionnaires between interviews. Following the evaluation, the primary interviewer presented the case at a two-hour diagnostic conference with colleagues from the research team. All available data (historical and concurrent) were reviewed and discussed at the conference: current and lifetime Axis I information, symptomatic status, social and developmental history, and personality features acknowledged on the Axis II interviews. In addition, significant others (e.g., romantic partners, family members, friends) were interviewed (when available) about patients&apos; characteristic personality features. Each PD symptom was rated on a scale of 0 to 2. The symptom counts used are the addition of these scores across symptoms for each PD. In Sample 1, we altered the NPD count by deleting one DSM-III-R symptom (i.e., reacts to criticism with feelings of rage, shame, or humiliation) in order to approximate the current DSM-IV conceptualization of NPD. PDQ-4+ (Sample 2)-The PDQ-4+ (32) is 99-item self-report measure of DSM-IV PDs and was used in Sample 2. The mean NPD symptom count was 1.98 (SD =1.61). Consensus ratings of impairment (Sample 1 and 2)-Consensus ratings of functional impairment were made separately for romantic relationships, other social relationships (e.g., friends, family members), occupational impairment, distressed caused to significant others (e.g., romantic partners, parents, children, close friends), and an overall impairment. The ratings ranged from 1 to 5 with higher scores indicating greater impairment (e.g., unable to work, no friends, no history of romantic relationships or history of chaotic relationships). As with PD ratings, all ratings were made using the LEAD model. As such, all information gleaned from the extensive interviews with participants and significant others (when available) pertaining to Axis I and II symptomatology, as well as past and present social, romantic, and educational/occupational histories was used to determine consensus ratings of impairment. Clinical ratings of depression, anxiety, and functioning (Sample 1 and 2)-Ratings of psychological distress were conducted with the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A). Functioning was assessed via the Global Assessment of Functioning (GAF). For both samples, intraclass correlation coefficients (ICCs) , computed with all available reliability data, documented good to excellent levels of reliability within our own group of judges. The ICCs for the HAM-D were .96 (Sample 1) and .98 (Sample 2. The ICCs for the HAM-A were .97 (Sample 1) and . 94 (Sample 2). The ICCs for the GAF were .75 (Sample 1) and .80 (Sample 2). Six-month follow-up-The assessment procedures completed at intake were used again at the 6-month follow-up, with the exception of the social/developmental history, which is not repeated. As with intake, all sources of available data were used to inform consensus ratings Statistical Analyses-First, Pearson&apos;s rs were used to examine the relations between narcissism and measures of anxiety, depression and various forms of functional impairment both concurrently and longitudinally. Next, we examined a model in which the prospective relations between narcissism and measures of psychopathology are mediated by impairment. Finally, we used hierarchical linear regression analyses to examine the unique predictive relations between Narcissism at Time 1 and distress and impairment measured at 6-month follow-up, after controlling for the effects of the other Cluster B PDs. Two-tailed p values were computed in all analyses. The distributions of all variables were examined and none showed signs of a significant departure from normality using existing guidelines (33; skewness !2.0 and/or kurtosis ! 7.0). As such, Pearson rs are used. Results Capturing narcissism: Concurrent and longitudinal relations Sex differences-There were significant sex differences for narcissism in Sample 1, t(150) =4.14, p&quot;.001, and Sample 2, t(149) =1.98, p&quot;.05, such that men had higher NPD symptom counts. All correlations presented in Relations with psychological distress and impairment: Concurrent and longitudinal findings-Concurrently, narcissism was related to ratings of depression and anxiety only in Sample 2 (see The pattern of findings between narcissism and impairment was quite consistent across assessments and samples. NPD symptoms were related to lower GAF scores in three of four instances. In addition, NPD symptoms were related to overall impairment, as well as all specific indices of impairment including impairment in romance, work, social life, and causing distress to significant others. Of the specific impairment scores, &quot;distress to significant others&quot; demonstrated the largest weighted effect sizes (rs =.46 and .48). Impairment as a mediator of the relationship between narcissism and psychological distress-We next examined the hypothesis that narcissism may be related to psychological distress primarily due to the impairment it causes in various life domains (see NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript narcissism on psychopathology decreased significantly after impairment was included in the model; in all six cases, narcissism was no longer significantly related to the distress outcome once impairment was included. In fact, the direct effect of narcissism was reduced by between 40% (anxiety, Sample 1) to 100% (depression, Sample 1; GAF, Sample 1; depression, Sample 2) Replicating mediation analyses with self-reported PDQ narcissism scores-In order to reduce concern that the previous results might be due, in part, to common method variance (i.e., consensus rating of both predictor and outcome variables), we replicated the same aforementioned model in Sample 2 but used self-reported symptoms of narcissism (i.e., PDQ) in place of consensus ratings of NPD. The results were nearly identical. Again, Sobel tests were used to test for statistical mediation. There was significant mediation by impairment for the relations between PDQ NPD and Time 2 depression (z = 2.78, p&quot;.01), Time 2 anxiety (z = 2.70, p&quot;.01), and Time 2 GAF scores (z = 2.93, p&quot;.01). The direct effect of narcissism was reduced by between 45% (anxiety) to 70% (GAF). Narcissism: Unique predictive relations of 6-month outcomes controlling for Cluster B PDs-Finally, we examined whether narcissism was a unique predictor of psychopathology and impairment once we controlled for the symptoms of antisocial, borderline and histrionic PDs (see Discussion Despite its placement in the last three editions of the DSM as one of only 10 officially recognized personality disorders, narcissistic PD has received scant empirical attention. Specifically, there has been little data presented that makes a clear and persuasive argument for its inclusion on the basis of the distress and impairment NPD causes. One strategy for dealing with this dearth of data on NPD would be to turn to the substantial empirical literature on narcissism that exists in the fields of social-personality psychology. However, this is problematic due to the use measures (e.g., NPI) that appear to capture only partially the construct as it is currently conceptualized by the DSM-IV and the reliance on undergraduate samples. Even if one were to rely on this body of literature, the central question would remain unresolved as to whether narcissistic individuals experience psychological distress (this literature suggests they do not; 21) or substantial impairment (24,26). The current study addresses these issues by presenting data on the concurrent and longitudinal relations between narcissistic PD and psychological distress and functional impairment in two clinical samples. These constructs are of vital importance in determining whether narcissism warrants continued presence in our diagnostic nomenclature. The current results suggest that NPD symptoms are significantly, but modestly, related to depression and anxiety both concurrently (Sample 2 only) and prospectively. NPD was also significantly and more strongly related to two general measures of impairment and more specific indices of impaired functioning in work, social, and romantic domains. These findings were consistent across samples and assessments (i.e., Times 1 and 2) and are consistent with findings regarding the broad array of impairment attached to other specific PDs (12-13). The GAF scores demonstrated the weakest relations, albeit still significant in 3 of 4 analyses. Across assessments, the weighted effect sizes were largest for impairment related to causing distress for important significant others. Indeed, NPD was only uniquely related to causing significant others pain and duress. This finding is consistent with knowledge gathered about the impact of narcissism in non-clinical samples, where narcissism is associated largely with costs suffered by others (24,26). We found evidence in both samples for a model in which the relation between narcissism and psychological distress was mediated by impaired functioning. That is, overall impairment accounted for the relationship between Time 1 narcissism and lower GAF scores, higher depression and anxiety at Time 2. These findings support the notion that depression and anxiety may not be endemic to narcissism but develop as a result of problems or failures in a variety of contexts. Narcissistic individuals may eventually feel sad or worried as they gain insight into the fact that they are not as successful in their work, love, and friendship relations as they hoped or in comparison to their peers. This finding might also partially explain the differences in the relationship between narcissism and psychological distress as reported in the clinical and social-personality literatures. Most narcissists would enter a clinical setting as a result of some form of failure in their personal or professional life, and this failure would eventually be expected to lead to psychological distress. Individuals with narcissistic personality traits who are able to avoid personal or professional failure, however, may both avoid clinical settings and report low levels of psychological distress. Limitations One potential