T55. DETECTING SEMANTIC DISTANCE ABNORMALITIES IN PSYCHOSIS: QUANTIFICATION OF WORD ASSOCIATIONS USING SEMANTIC SPACE MODELING

Abstract Background Language Disorganisation is central to the conceptualization of psychosis. Disruptions in semantic processing have been observed both as a “state”, and a “trait” phenomena in psychotic disorders. Quantification of semantic abnormalities have been improved with recent advances in semantic modeling. The current study applied such computational methods on a word association task, using immediate response to cue words to explore semantic associations. We employed a longitudinal design to investigate semantic relationships during a psychotic episode compared with the same patients after remission six months later, in order to clarify the state-trait status of the semantic variables, and their relationships with clinical symptoms. We hypothesized that semantic distance would be significantly greater in patients than controls at baseline, and would decrease upon follow-up. Methods A continued word association task (WAT) was employed to elicit three associations per cue from a set of 200 cue-words. The set of cues were previously established as being representative of words in general speech, in terms of valence, concreteness and part-of-speech composition. The task was administered to 47 patients with schizophrenia spectrum disorders and 44 matched healthy control participants. Data was collected at two time points, at baseline when patients were actively psychotic and then at 6-months follow-up. In addition, extensive clinical and cognitive measures were collected at both time points. Patterns of word associations were explored using vector representations, derived from Word2Vec, that encompass semantic meaning. Semantic distance of each cue-response pairing is defined using the cosine angle of their vectors. Changes in semantic distance were further examined on their correlation with symptom change over time. Results There was a significant interaction between group and time point on semantic distance (F = 6.865, p = 0.009), where measures of the semantic distance of patients’ responses were significantly greater than healthy controls at both time-points (p < 0.001).There is a significant time effect: the semantic distance reduced significantly over time (p < 0.001). Within the patient group, a change in semantic distance was correlated with symptom change over time, specifically with general psychopathology (p =0.024), depressive (p = 0.046) and manic symptoms (p < 0.01). Discussion Measures of semantic distance were significantly greater in patients both at baseline during a psychotic episode, and at follow-up upon clinical remission. There is a significant but not full normalization of semantic distance upon remission. Increase in semantic distance is therefore both a state and a trait marker in psychosis. We have employed a novel technique to quantify semantic distance of a word association task using Word2Vec to generate vector representations of responses in a high-dimensional semantic space. The findings illustrate the feasibility of applying Word2Vec to a word association task to detect subtle changes in language. Subsequent research possibilities using this approach includes exploration of the semantic content of responses, by grouping similar meaning responses into conceptual clusters, and its correlation with symptom change.

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T3 Are Burns a Chronic Condition: Examining Physical and Mental Functioning up to 20 Years After Injury

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.002 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S2-S3

Author(s):

Callie Abouzeid ◽

Audrey E Wolfe ◽

Gretchen J Carrougher ◽

Nicole S Gibran ◽

Radha K Holavanahalli ◽

...

Keyword(s):

Mental Health ◽

Hospital Stay ◽

National Database ◽

Time Points ◽

Patient Reported ◽

Burn Survivors ◽

Population Demographic ◽

The Impact ◽

Over Time

Abstract Introduction Burn survivors often face many long-term physical and psychological symptoms associated with their injury. To date, however, few studies have examined the impact of burn injuries on quality of life beyond 2 years post-injury. The purpose of this study is to examine the physical and mental well-being of burn survivors up to 20 years after injury. Methods Data from the Burn Model System National Database (1997–2020) were analyzed. Patient-reported outcome measures were collected at discharge with a recall of preinjury status, and then at 5, 10, 15, and 20 years after injury. Outcomes examined were the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Short Form-12. Trajectories were developed using linear mixed methods model with repeated measures of PCS and MCS scores over time and controlling for demographic and clinical variables. The model fitted score trajectory was generated with 95% confidence intervals to demonstrate score changes over time and associations with covariates. Results The study population included 420 adult burn survivors with a mean age of 42.4 years. The population was mainly male (66%) and white (76.4%) with a mean burn size of 21.5% and length of hospital stay of 31.3 days. Higher PCS scores were associated with follow-up time points closer to injury, shorter hospital stay, and younger age. Similarly, higher MCS scores were associated with earlier follow-up time points, shorter hospital stay, female gender, and non-perineal burns. MCS trajectories are demonstrated in the Figure. Conclusions Burn survivors’ physical and mental health worsened over time. Such a trend is different from previous reported results for mental health in the general population. Demographic and clinical predictors of recovery over time are identified.

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Long-Term Reactions to the Loss of a Close Friend in an Extreme Terror Incident

OMEGA - Journal of Death and Dying ◽

10.1177/0030222818814052 ◽

2018 ◽

Vol 82 (3) ◽

pp. 351-369 ◽

Cited By ~ 1

Author(s):

Iren Johnsen ◽

Kari Dyregrov ◽

Stig Berge Matthiesen ◽

Jon Christian Laberg

Keyword(s):

Longitudinal Studies ◽

Quantitative Data ◽

Close Friend ◽

Traumatic Death ◽

Time Points ◽

Grief Reactions ◽

Over Time ◽

Avoidant Behavior

This article presents results from one of the first longitudinal studies exploring the effects of losing a close friend to traumatic death, focusing on complicated grief over time and how this is affected by avoidant behavior and rumination about the loss. The sample consists of 88 persons (76% women and 24% men, mean age = 21) who lost a close friend in the Utøya killings in Norway on July 22, 2011.Quantitative data were collected at three time-points; 18, 28, and 40 months postloss. Main findings are that bereaved friends are heavily impacted by the loss and their grief reactions are affected negatively by avoidant behavior and rumination. This indicates that close bereaved friends are a group to be aware of and that there is a need for better strategies for identifying individuals in need for follow-up.

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Changes of trace element status during aging: results of the EPIC-Potsdam cohort study

European Journal of Nutrition ◽

10.1007/s00394-019-02143-w ◽

2019 ◽

Vol 59 (7) ◽

pp. 3045-3058 ◽

Cited By ~ 6

Author(s):

Julia Baudry ◽

Johannes F. Kopp ◽

Heiner Boeing ◽

Anna P. Kipp ◽

Tanja Schwerdtle ◽

...

Keyword(s):

Reference Ranges ◽

Linear Regression Models ◽

Serum Samples ◽

Time Points ◽

Supplement Use ◽

Healthy Elderly ◽

Age Related ◽

Longitudinal Variability ◽

Over Time

Abstract Purpose We aimed to evaluate age-dependent changes of six trace elements (TE) [manganese (Mn), iron (Fe), zinc (Zn), copper (Cu), iodine (I), and selenium (Se)] over a 20-year period. Methods TE concentrations were determined using repeated serum samples taken at baseline and after 20 years of follow-up from 219 healthy participants of the EPIC-Potsdam study, using inductively coupled plasma tandem mass spectrometry. For each TE, absolute and relative differences were calculated between the two time points, as well as the proportion of individuals within normal reference ranges. Interdependence between age-related TE differences was investigated using principal component analysis (PCA). Relationships between selected factors (lifestyle, sociodemographic, anthropometric factors, and hypertension) and corresponding TE longitudinal variability were examined using multivariable linear regression models. Results Median age of our study sample was 58.32 years (4.42) at baseline and 40% were females. Median Mn, Zn, Se concentrations and Se to Cu ratio significantly decreased during aging while median Fe, Cu, I concentrations and Cu to Zn ratio significantly increased. A substantial percentage of the participants, at both time points, had Zn concentrations below the reference range. The first PCA-extracted factor reflected the correlated decline in both Mn and Zn over time while the second factor reflected the observed (on average) increase in both Cu and I over time. Overall, none of the investigated factors were strong determinants of TE longitudinal variability, except possibly dietary supplement use, and alcohol use for Fe. Conclusions In conclusion, in this population-based study of healthy elderly, decrease in Mn, Zn, and Se concentrations and increase in Fe, Cu, and I concentrations were observed over 20 years of follow-up. Further research is required to investigate dietary determinants and markers of TE status as well as the relationships between TE profiles and the risk of age-related diseases.

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Persistent Cytotoxic T Lymphocyte Expansions after Allogeneic Hematopoietic Stem Cell Transplantation: Kinetics, Clinical Impact and Absence of STAT3 Mutations

Blood ◽

10.1182/blood.v126.23.3153.3153 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3153-3153

Author(s):

Julia Muñoz-Ballester ◽

Tzu Hua Chen-Liang ◽

Ana María Hurtado ◽

Pastora Iniesta ◽

María Dolores García-Malo ◽

...

Keyword(s):

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Linear Representation ◽

Time Points ◽

Linear Plot ◽

Line Slope ◽

Stat3 Mutations ◽

Over Time

Abstract Thymic-independent peripheral expansion of CD8+ cells derived from the graft in the initial stage of post-HSCT immune recovery is a well-known physiological event. Nevertheless, the description of symptomatic LGL leukemias and aggressive malignant cases in this setting may generate uncertainty, mostly in those cases in which the cytotoxic T lymphocyte expansion CTLe persists beyond the early transplantation period. We aimed to assess the nature of CTLe in adults during the post-alloHSCT period in a series of 154 patients with a long term surveillance. We studied the longitudinal kinetics of those expansions, their relation to clinical events, and their phenotypic and molecular features, including recently reported CTL leukemia-STAT3 mutations. In our study, trying to adhere to the WHO annotation of T-LGL, we considered two definitions for a CTL expansion: an absolute increase (≥ 2000 x109/L), and a relative expansion (a CD8/CD4 ratio ≥ 1.5), persisting more than six months in both cases. Persistent relative CTLe cases are frequent (49%) and related with timoglobulin prophylaxis (p≤0.001), acute graft versus host disease (GVHD, p=0.02), reduced intensity conditioning (p=0.04) and fungal and viral infections in the early post-HSCT. No differences in the number of serious infectious events from day 180 was found. Absolute CTLe are scarce (9%), related with chronic GVHD and absence of relapses. TCR rearrangement was reported as clonal and oligoclonal in the majority of patients with CTLe. We studied in a cross sectional manner with an extended immunophenotypic panel 17 patients: 5 patients with an absolute CTLe and 12 cases with a relative CTLe. A similar cytotoxic T αβ-effector phenotype was observed in all cases, with slight differences in the expression of CD25, CD16 and 1a. One patient with a relative CTLe expressed CD56 intensely: his ratio normalized at day 730 and no immune-related events were recorded. DNA stored during the post-alloHSCT setting was available from 68/75 relative CTLe patients (14/14 absolute CTLe cases). All of them went through molecular TCR rearrangement and STAT3 exon 21 mutations determination. In the relative CTLe cohort, TCR rearrangement was described as clonal, oligoclonal or polyclonal in 77%, 16% and 7%, respectively. Regarding absolute CTLe patients, TCR rearrangement was described as clonal in all the patients (n=14) of this subset. To increase the sensibility of the Sanger PCR, it was performed on DNA from CD3+ sorted cells in 54 out of 68 cases. No STAT3 mutation could be found in the CD3+ sorted fraction of relative or absolute defined CTLe. Not using an absolute threshold would establish a diagnosis of a persistent CTL expansion in 49% of our cohort of allo-transplanted patients. Additional diagnostic tools, as an effector phenotype, the presence of a NK marker or a monoclonal TCR rearrangement would not reduce significantly that percentage: CD57 was invariably expressed in CTLe cases, and 80% of our patients with expansions showed a TCR monoclonal pattern. STAT3 mutations resulting in persistent proliferation of CTL clones are a frequent event in large granular lymphocytic leukemia, and those clones have also been described in autoimmunity-driven disorders as acquired aplastic anemia and hypocellular myelodysplastic syndromes. We establish in this study the absence of exon 21 STAT3 mutations in the persistent CTL expansions found in a large series of patients with a long-term post-alloHSCT surveillance. The absence of STAT3 mutations and the CD8/CD4 declining longitudinal kinetics in the late period, supports its benign nature, expressed clinically by the null detrimental impact of these expansions on post-transplant outcome and/or serious infectious events. Figure 1. Relative and absolute CTLe kinetics. A) Linear representation over time of the CD8/CD4 ratio in the 75 patients with relative CTLe. B) Trend linear plot of 25 patients with a relative CTLe and a follow up of, at least, 1440 days from transplantation. Each line depicts a patientxs longitudinally measured CD8/CD4 ratio. Patients are grouped by similar pattern of ratio behaviour through follow up. The line "slope" depicts the magnitude of the change between time points. C) Linear representation over time of the CD3/CD8 count in PB in the 14 patients with an absolute CTLe. D) Trend linear plot illustrating the CD8/CD4 ratio behaviour of the 14 patients with an absolute CTLe. Figure 1. Relative and absolute CTLe kinetics. A) Linear representation over time of the CD8/CD4 ratio in the 75 patients with relative CTLe. B) Trend linear plot of 25 patients with a relative CTLe and a follow up of, at least, 1440 days from transplantation. Each line depicts a patientxs longitudinally measured CD8/CD4 ratio. Patients are grouped by similar pattern of ratio behaviour through follow up. The line "slope" depicts the magnitude of the change between time points. C) Linear representation over time of the CD3/CD8 count in PB in the 14 patients with an absolute CTLe. D) Trend linear plot illustrating the CD8/CD4 ratio behaviour of the 14 patients with an absolute CTLe. Disclosures No relevant conflicts of interest to declare.

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Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative Treatment for Knee Cartilage Injuries

The American Journal of Sports Medicine ◽

10.1177/0363546516677255 ◽

2017 ◽

Vol 45 (4) ◽

pp. 875-883 ◽

Cited By ~ 19

Author(s):

Devon E. Anderson ◽

Riley J. Williams ◽

Thomas M. DeBerardino ◽

Dean C. Taylor ◽

C. Benjamin Ma ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Clinical Trials ◽

Magnetic Resonance ◽

Resonance Imaging ◽

Repair Tissue ◽

Time Points ◽

Cartilage Lesions ◽

Articular Cartilage Lesions ◽

Over Time

Background: Autologous cartilage tissue implants, including the NeoCart implant, are intended to repair focal articular cartilage lesions. Short-term results from United States Food and Drug Administration (FDA) phase I and phase II clinical trials indicated that the NeoCart implant was safe when surgically applied as a cell-based therapy and efficacious compared with microfracture. Hypothesis: Quantitative magnetic resonance imaging (MRI) analysis would reveal NeoCart tissue maturation through to 60-month follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with symptomatic full-thickness cartilage lesions of the distal femoral condyle were treated with NeoCart in FDA clinical trials. Safety and efficacy were evaluated prospectively by MRI and clinical patient-reported outcomes (PROs) through to 60-month follow-up. Qualitative MRI metrics were quantified according to modified MOCART (magnetic resonance observation of cartilage repair tissue) criteria, with an independent evaluation of repair tissue signal intensity. Subjective PROs and objective range of motion (ROM) were obtained at baseline and through to 60 months. Results: Twenty-nine patients treated with NeoCart were observed over a mean of 52.0 ± 15.5 months (median, 60 months). MOCART analyses indicated significant improvement ( P < .001) in cartilage quality from 3 to 24 months, with stabilization from 24 to 60 months. Signal intensity of the repair tissue evolved from hyperintense at early follow-up to isointense after 6 months and to hypointense after 24 months. The temporal progression toward hypointense T2 signals at later time points observed here indicated a further reorganization of the repair tissue toward a dense tissue that was less similar to the surrounding native tissue. However, 80% of patients showed evidence of subchondral bone changes on MRI at all time points; 4 patients (14%) showed no improvement of MRI criteria. Compared with baseline values, significant improvement ( P < .001) was seen in PROs (mean [±SD] baseline to mean [±SD] final follow-up), including the International Knee Documentation Committee score (47.9 ± 17.4 to 75.5 ± 22.1), physical component summary of the Short Form–36 (40.5 ± 7.2 to 51.4 ± 8.1), and all 5 domains of the Knee injury and Osteoarthritis Outcome Score (Pain: 64.8 ± 12.1 to 86.1 ± 17.3; Activities of Daily Living: 75.5 ± 14.8 to 91.6 ± 13.8; Quality of Life: 28.6 ± 15.5 to 69.4 ± 28.0; Symptoms: 65.8 ± 13.8 to 86.6 ± 13.4; Sports and Recreation: 41.4 ± 24.3 to 72.4 ± 28.8). Significant ( P < .0001) decreases from baseline scores for the visual analog scale for pain (34.6 ± 22.5) were seen by 6 months and sustained at final follow-up (14.3 ± 18.4). ROM significantly ( P < .0001) improved from baseline (131.5° ± 7.9°) to final follow-up (140.7° ± 6.3°). Conclusion: Longitudinal MRI analysis demonstrated that NeoCart-based repair tissue is durable and evolves over time. For a majority of patients, this progression trended from an initial hyperintense signal to a hypointense signal at later follow-ups. Changes in radiographic measures over time corresponded with improvement in clinical measures, with maximum benefits experienced at 24-month follow-up. Similarly, clinical efficacy for the total cohort, determined by clinical outcome scores, reached a maximum at 24 months without decline to 60 months. Results from safety and exploratory clinical trials indicate that NeoCart is a safe and effective treatment for articular cartilage lesions through to 5-year follow-up. Registration: NCT00548119 ( ClinicalTrials.gov identifier).

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The radiological interpretation of possible microbleeds after moderate or severe traumatic brain injury: a longitudinal study

Neuroradiology ◽

10.1007/s00234-021-02839-z ◽

2021 ◽

Author(s):

Anke W. van der Eerden ◽

Thomas L. A. van den Heuvel ◽

Marnix C. Maas ◽

Priya Vart ◽

Pieter E. Vos ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Longitudinal Study ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Time Points ◽

Computer Aided ◽

Clinical Consequences ◽

Severe Tbi ◽

Over Time

Abstract Introduction In order to augment the certainty of the radiological interpretation of “possible microbleeds” after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. Methods Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. Results Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. Conclusions Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.

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Optimum timing to assess ablation lesions with Late Gadolinium Enhancement MRl

EP Europace ◽

10.1093/europace/euab116.079 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

TF Althoff ◽

P Garre ◽

G Caixal ◽

S Prat ◽

J Perea ◽

...

Keyword(s):

Late Gadolinium Enhancement ◽

Positive Predictive Value ◽

Predictive Value ◽

Individual Development ◽

Atrial Fibrosis ◽

Gadolinium Enhancement ◽

Time Points ◽

Fibrotic Tissue ◽

Over Time

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Spanish Government, Madrid, Spain [FIS_PI16/00435 Background Late gadolinium enhancement MRI (LGE-MRI) is increasingly used to detect native as well as ablation-induced atrial fibrosis in the context of atrial fibrillation (AF). However, cardiac fibrotic tissue including ablation lesions is subject to sustained remodeling, and neither the development of ablation-induced fibrosis over time nor the capability of LGE-MRI to detect it at different stages of scar formation have been defined. We sought to define the long-term development of ablation-induced atrial fibrosis and to validate LGE-MRI for the assessment of ablation lesions at different time points. Methods Patients with first-time AF ablation and an early follow-up LGE-MRI (3 months post ablation) and a late follow-up LGE-MRI (>12 months post ablation) were included. LGE-MRI data were postprocessed for quantification of fibrotic tissue using the ADAS 3D software. In the majority of patients high-density electroanatomical mapping (EAM), performed in a repeat procedure served as a reference. Results 22 consecutive patients fulfilling the inclusion criteria were analysed retrospectively. In the LGE-MRI 3 months post ablation an average of 91.7 ± 7.0% of the ablation lines" circumference displayed late gadolinium enhancement (LGE) reflecting ablation-induced fibrosis, whereas in the late follow-up LGE-MRI, at a median of 28 months post ablation, only 62.8 ± 25.0% of the ablation lines" circumference was covered by LGE (p < 0.0001) (see figure for representative examples and individual development of LGE coverage over time). This decrease of LGE coverage of the ablation lines was also reflected by an increase in the median number of LGE-MRI-predicted gaps per circumferential ablation line from 4 (3 months) to 10 (28 months). These data may suggest a decrease of ablation-induced fibrosis over time. However, EAM subsequent to the late follow-up LGE-MRI, which was performed in 18 of the 22 patients, indicates that it was not ablation-induced fibrosis that decreased over time, but rather the capability of LGE-MRI to detect it. In 95% of the pulmonary vein segments in which the late follow-up LGE-MRI (28 months) indicated a disappearance of local ablation-induced fibrosis, EAM demonstrated durable lesions consistent with the 3-months LGE-MRI. In line with this observation, the overall agreement of EAM at the repeat procedures with the 3-months LGE-MRI regarding the prediction of ablation-induced fibrosis and functional gaps was good (K 0.74; p< 0.0001, positive predictive value 93%), whereas the agreement with the LGE-MRI at 28-months was only weak (K 0.29; p < 0.0001, positive predictive value 63%). Conclusions Our results indicate that while ablation-induced atrial fibrosis appears to remain rather constant over time, LGE-MRI loses some of its capability to detect it. Thus, LGE-MRI 3 months post ablation may be more accurate in the detection of durable ablation lesions than LGE-MRI at later time points more than 12 months after ablation. Abstract Figure

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Cognitive Functioning and Schizotypy: A Four-Years Study

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.613015 ◽

2021 ◽

Vol 11 ◽

Author(s):

Penny Karamaouna ◽

Chrysoula Zouraraki ◽

Stella G. Giakoumaki

Keyword(s):

Cognitive Functioning ◽

Response Inhibition ◽

Processing Speed ◽

Control Group ◽

Set Shifting ◽

Ample Evidence ◽

Time Points ◽

Wide Range ◽

Over Time

Although there is ample evidence from cross-sectional studies indicating cognitive deficits in high schizotypal individuals that resemble the cognitive profile of schizophrenia-spectrum patients, there is still lack of evidence by longitudinal/follow-up studies. The present study included assessments of schizotypal traits and a wide range of cognitive functions at two time points (baseline and 4-years assessments) in order to examine (a) their stability over time, (b) the predictive value of baseline schizotypy on cognition at follow-up and (c) differences in cognition between the two time points in high negative schizotypal and control individuals. Only high negative schizotypal individuals were compared with controls due to the limited number of participants falling in the other schizotypal groups at follow-up. Seventy participants (mean age: 36.17; 70% females) were assessed at baseline and follow-up. Schizotypal traits were evaluated with the Schizotypal Personality Questionnaire. We found that schizotypal traits decreased over time, except in a sub-group of participants (“schizotypy congruent”) that includes individuals who consistently meet normative criteria of inclusion in either a schizotypal or control group. In these individuals, negative schizotypy and aspects of cognitive-perceptual and disorganized schizotypy remained stable. The stability of cognitive functioning also varied over time: response inhibition, aspects of cued attention switching, set-shifting and phonemic/semantic verbal fluency improved at follow-up. High negative schizotypy at baseline predicted poorer response inhibition and semantic switching at follow-up while high disorganized schizotypy predicted poorer semantic processing and complex processing speed/set-shifting. The between-group analyses revealed that response inhibition, set-shifting and complex processing speed/set-shifting were poorer in negative schizotypals compared with controls at both time points, while maintaining set and semantic switching were poorer only at follow-up. Taken together, the findings show differential stability of the schizotypal traits over time and indicate that different aspects of schizotypy predict a different pattern of neuropsychological task performance during a 4-years time window. These results are of significant use in the formulation of targeted early-intervention strategies for high-risk populations.

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Factor structure of the SDQ and longitudinal associations from pre-school to pre-teen in New Zealand

PLoS ONE ◽

10.1371/journal.pone.0247932 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247932

Author(s):

John M. D. Thompson ◽

Rebecca F. Slykerman ◽

Clare R. Wall ◽

Rinki Murphy ◽

Edwin A. Mitchell ◽

...

Keyword(s):

Factor Analysis ◽

New Zealand ◽

Factor Structure ◽

Internal Consistency ◽

Strengths And Difficulties Questionnaire ◽

Self Report ◽

Time Points ◽

Strengths And Difficulties ◽

Over Time

Objective The objective of this study was to assess the validity of the Strengths and Difficulties Questionnaire in a cohort of New Zealand children followed from birth to the age of eleven. The study also aimed to assess the stability of the child data in relation to behavioural outcomes during this period. Methods Children in the Auckland Birthweight Collaborative Study were assessed at approximately 3½, 7 and 11 years of age. At all time-points parents completed the parent version of the Strengths and Difficulties Questionnaire, and the children themselves completed the self-report version at 11 years of age. The validity and internal consistency were assessed using exploratory factor analysis, Cronbach’s alpha, and McDonald’s Omega. Cross tabulations and Chi-square statistics were used to determine whether Total Difficulty scores, as per accepted cut-offs, remained stable over time (between normal and abnormal/borderline categories). Results The factor structure remained relatively consistent across all three time-points, though several questions did not load as per the originally published factor analysis at the earliest age. The internal consistency of the Strengths and Difficulties Questionnaire was good at all time-points and for parent- and child-completed versions. There was low agreement in the total scores between time points. Conclusions The factor analysis shows that the Strengths and Difficulties Questionnaire has a similar factor structure, particularly in older ages, to that previously published and shows good internal consistency. At the pre-school follow up, a larger than expected proportion of children were identified with high scores, particularly in the conduct sub-scale. Children’s behaviour changes over time, with only poor to moderate agreement between those identified as abnormal or borderline over the longitudinal follow up.

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Genomic Evolution of Multiple Myeloma In Vivo over Time.

Blood ◽

10.1182/blood.v108.11.3400.3400 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3400-3400

Author(s):

Yu-Tzu Tai ◽

Benjamin King ◽

Cheng Li ◽

XianFeng Li ◽

Peter Burger ◽

...

Keyword(s):

Drug Resistance ◽

Mononuclear Cells ◽

Base Line ◽

Genomic Evolution ◽

Peripheral Blood Mononuclear ◽

Myeloma Cells ◽

Time Points ◽

Over Time

Abstract Genetic instability is an important feature of malignant cells, specifically in multiple myeloma (MM). This instability, by activation of oncogene or deletion of tumor suppressor genes, plays an important role in oncogenesis. The ongoing genetic instability is responsible for tumor progression, acquisition of invasiveness, and development of drug resistance, as well as eventual mortality. We have previously demonstrated that MM cells have elevated homologous recombination activity that leads to acquisition of new genomic changes over time and is associated with development of drug resistance (Blood2004; 104: 3409). However, such genomic evolution in patient samples has not been documented. Here we have performed genome wide loss of heterozygosity (LOH) assay, using high-density oligonucleotide arrays capable of measuring up to 250K single nucleotide polymorphisms (SNP) loci and able to analyze small areas of gains or losses as an indicator of genomic instability to determine ongoing development of new changes that may reflect instability. We have evaluated nine MM patients with purified myeloma cells obtained at two time points, atleast six months apart. CD138-expressing myeloma cells from these patients were purified and their peripheral blood mononuclear cells were also obtained. Genomic DNA from these cells was digested with StyI, PCR amplified and hybridized to 250K SNP array. Results from CD138+ myeloma cells from two time points were compared with each other as well as with sample from normal peripheral blood mononuclear cells using the dChip software for LOH and copy number analysis and areas of deletions and amplifications. The changes at the first time point were considered as base line, and the subsequent sample was considered as test sample where acquisition of new changes was evaluated compared to base line. In two patients we had three samples available on a serial basis. We have observed that myeloma cells from the second time point demonstrated significant new areas of genomic change with acquisition of mean 4467 (range 79 to 18998) new LOH loci from base line sample. Of theses new areas of change, 41 SNP loci were found to be present in more than three patient samples indicating recurrent loci of interest in regards to progression and/or development of drug resistance. In 2 patients with 3 serial samples, we observed serial increase in acquisition of new SNPs, 4947 and 18998 at first follow up and 531 and 5275 at second follow up suggesting cumulative accumulation of new genetic change. The reproducible area of new acquisition interestingly involves the area with chromosome 1 and 8 that may have significant role in the pathogenesis and progression of the disease. We are currently obtaining the gene expression profile from these time points to identify expression changes correlating with the observed genomic changes on follow up samples. In summary our results confirm genomic evolution of myeloma in vivo over time and provide means to identify molecular targets associated with progression of MM that can be utilized to inhibit progression of the disease and possibly development of drug resistance.

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