Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines : randomized, double-blind study in malaria-naïve adults

This phase II, randomized, double-blind study evaluated the immunogenicity of RTS, S vaccines containing Adjuvant System AS 01 or AS 02 as compared with non-adjuvanted RTS, S in healthy, malaria-naive adults (NCT00443131). Thirty-six subjects were randomized (1:1:1) to receive RTS, S/AS 01, RTS, S/AS 02, or RTS, S/saline at months 0, 1, and 2. Antibody responses to Plasmodium falciparum circumsporozoite (CS) and hepatitis B surface (HBs) antigens were assessed and cell-mediated immune responses evaluated by flow cytometry using intracellular cytokine staining on peripheral blood mononuclear cells. Anti-CS antibody avidity was also characterized. Safety and reactogenicity after each vaccine dose were monitored. One month after the third vaccine dose, RTS, S/AS 01 (160.3 EU/mL [95%CI: 114.1-225.4]) and RTS, S/AS 02 (77.4 EU/mL (95%CI: 47.3-126.7)) recipients had significantly higher anti-CS antibody geometric mean titers (GMTs) than recipients of RTS, S/saline (12.2 EU/mL (95%CI: 4.8-30.7); P < 0.0001 and P = 0.0011, respectively). The anti-CS antibody GMT was significantly higher with RTS, S/AS 01 than with RTS, S/AS 02 (P = 0.0135). Anti-CS antibody avidity was in the same range in all groups. CS- and HBs-specific CD4(+) T cell responses were greater for both RTS, S/AS groups than for the RTS, S/saline group. Reactogenicity was in general higher for RTS, S/AS compared with RTS, S/saline. Most grade 3 solicited adverse events (AEs) were of short duration and grade 3 solicited general AEs were infrequent in the 3 groups. No serious adverse events were reported. In conclusion, in comparison with non-adjuvanted RTS, S, both RTS, S/AS vaccines exhibited better CS-specific immune responses. The anti-CS antibody response was significantly higher with RTS, S/AS 01 than with RTS, S/AS 02. The adjuvanted vaccines had acceptable safety profiles

Measurement Properties of the Full and Brief Version of the Work Rehabilitation Questionnaire in Persons with Physical Disabilities

Purpose The Work Rehabilitation Questionnaire (WORQ) is a self-report vocational rehabilitation assessment. A comprehensive (WORQ-FULL) and a brief version (WORQ-BRIEF) are available. The purpose of this study was to investigate measurement properties of both versions in persons with physical disabilities. Methods Cross sectional and test-retest design. Adults with physical disabilities in vocational rehabilitation were included. Internal consistency (Cronbach's alpha), test-retest reliability (intra-class correlation; ICC), agreement between sessions (Bland-Altman Plots), criterion validity (ICC and agreement with Bland-Altman Plots between WORQ-FULL and WORQ-BRIEF) and convergent validity with the Work Ability Index -Single item (WAS) and the EuroQOL 5D-5L were analyzed. Results Out of the 91 individuals who agreed to participate, 74 (81%) returned questionnaire T1 and 49 (54%) participants returned questionnaire T2 within the maximum time interval (= 27 days). At T2, 28 (57%) participants reported no medical changes compared to T1. Median age was 49 (IQR 40-60), 57% were male, 47% had experienced a stroke and 27% a spinal cord injury (n = 49). Internal consistency was good: 0.95/0.95/0.94 for the WORQ-FULL and 0.88/0.89/0.85 for the WORQ-BRIEF (n = 74/n = 48/n = 28, respectively). Test-retest reliabilitywas good: ICC = 0.86/0.85 for the WORQ-FULL and ICC = 0.87/0.86 for the WORQ-BRIEF (n = 49/ n = 28). Bland Altman plots suggested a higher score at T1. As for criterion validity of the WORQ-FULL versus the WORQ-BRIEF, ICC was good (ICC = 0.84; n = 74), however Bland Altman plots indicated potential bias. Correlations with the WAS/EuroQOL 5D-5L were variable: r = -0.24/r = -0.57 (WORQ-FULL) and r = -0.28/-0.65 (WORQ-BRIEF). Conclusions The WORQ showed good internal consistency and test-retest reliability. Agreement demonstrated large score differences are needed to indicate change beyond random chance at individual level, whereas small changes are sufficient at group level. Criterion validity of the WORQ-FULL versus the WORQ-BRIEF was supported, however, agreement demonstrated moderate to large score differences are needed to indicate change beyond random chance at individual level, whereas small changes are sufficient at group level. This indicates the WORQ-FULL and WORQ-BRIEF are better not used interchangeably. Correlation analyses provided better insight in the validity of the WORQ. Convergent validity was supported for the WORQ-BRIEF with the EuroQoL 5D-5L (r = -0.65)

Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon-ribavirin combination therapy after 4 weeks of treatment

Background Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment. Aim To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy. Methods Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 mu g pegylated interferon (PEG-IFN)-alpha-2a (weekly) and ribavirin 1000-1200mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed. Results Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P=0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (= 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-alpha-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis). Conclusion The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-alpha-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml. Eur J Gastroenterol Hepatol 22:1443-1448 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Rapid phosphatidic acid accumulation in response to low temperature stress in Arabidopsis is generated through diacylglycerol kinase.

Phosphatidic acid (PtdOH) is emerging as an important signaling lipid in abiotic stress responses in plants. The effect of cold stress was monitored using (32)P-labeled seedlings and leaf discs of Arabidopsis thaliana. Low, non-freezing temperatures were found to trigger a very rapid (32)P-PtdOH increase, peaking within 2 and 5 min, respectively. In principle, PtdOH can be generated through three different pathways, i.e., (1) via de novo phospholipid biosynthesis (through acylation of lyso-PtdOH), (2) via phospholipase D hydrolysis of structural phospholipids, or (3) via phosphorylation of diacylglycerol (DAG) by DAG kinase (DGK). Using a differential (32)P-labeling protocol and a PLD-transphosphatidylation assay, evidence is provided that the rapid (32)P-PtdOH response was primarily generated through DGK. A simultaneous decrease in the levels of (32)P-PtdInsP, correlating in time, temperature dependency, and magnitude with the increase in (32)P-PtdOH, suggested that a PtdInsP-hydrolyzing PLC generated the DAG in this reaction. Testing T-DNA insertion lines available for the seven DGK genes, revealed no clear changes in (32)P-PtdOH responses, suggesting functional redundancy. Similarly, known cold-stress mutants were analyzed to investigate whether the PtdOH response acted downstream of the respective gene products. The hos1, los1, and fry1 mutants were found to exhibit normal PtdOH responses. Slight changes were found for ice1, snow1, and the overexpression line Super-ICE1, however, this was not cold-specific and likely due to pleiotropic effects. A tentative model illustrating direct cold effects on phospholipid metabolism is presented

Content validity of the Work Rehabilitation Questionnaire (WORQ) for persons with spinal cord injury:A mixed methods study

STUDY DESIGN: Mixed methods. OBJECTIVES: The aim of our study was to investigate the content validity of the Work Rehabilitation Questionnaire (WORQ) for use in persons with post-acute and chronic spinal cord injury (SCI). SETTING: A university-based Rehabilitation Center in The Netherlands. METHODS: Contents of the WORQ, brief ICF core sets for SCI for post-acute care and for chronic situation were compared with semi-guided interviews with persons with SCI and controlled for relevance by SCI rehabilitation professionals in two group meetings. RESULTS: Fourteen interviews with persons with SCI were performed. Two group meetings with 8 and 9 SCI rehabilitation professionals were held. Thirty seven of the 46 ICF categories (80%) of the WORQ were confirmed by both sources: mentioned in interviews with persons with SCI and considered important by the SCI professionals. The remaining 9 categories (20%) were confirmed by either the persons with SCI or the SCI professionals. Fourteen ICF categories that are part of the brief ICF core set for SCI for acute care and/or chronic situation, however are not part of the WORQ, have revealed importance by persons with SCI and SCI professionals. CONCLUSION: Our study confirms that most categories of the WORQ are important to consider for VR in persons with SCI, however, there are ICF categories that are absent in the WORQ and deemed relevant for use in VR in persons with SCI. Consequently, the content validity of the WORQ without additional items is insufficient for persons with SCI

Prediction of Psychological Distress Among Persons With Spinal Cord Injury or Acquired Brain Injury and Their Significant Others

Objectives: To identify intra- and interpersonal sociodemographic, injury-related, and psychological variables measured at admission of inpatient rehabilitation that predict psychological distress among dyads of individuals with spinal cord injury (SCI) or acquired brain injury (ABI) and their significant others (ie, individuals close to the individual with a disability, mostly family members) 6 months after discharge. Differences in predictors were investigated for persons with SCI or ABI and their significant others and were compared between diagnoses.Design: Prospective longitudinal study.Setting: Twelve Dutch rehabilitation centers.Participants: Dyads (N= 157) consisting of adults with SCI or ABI who were admitted to inpatient rehabilitation and their adult significant others.Interventions: Not applicable.Main Outcome Measures: Psychological distress (Hospital Anxiety and Depression Scale).Results: Sociodemographic and injury-related variables were not or were only weakly associated with psychological distress among individuals with SCI or ABI and their significant others 6 months after discharge. Bivariately, higher baseline psychological distress, lower scores on adaptive psychological characteristics (combination of self-efficacy, proactive coping, purpose in life, resilience), and higher scores on maladaptive psychological characteristics (combination of passive coping, neuroticism, appraisals of threat and loss) were related to higher psychological distress, as well as crosswise between individuals with SCI or ABI and their significant others, although less strongly. Combined prediction models showed that psychological distress among persons with SCI or ABI was predicted by education level of their significant other, their own baseline psychological distress, and their own maladaptive psychological characteristics (explained variance, 41.9%). Among significant others, only their own baseline psychological distress predicted psychological distress (explained variance, 40.4%). Results were comparable across diagnoses.Conclusions: Although a dyadic connection was shown, primarily one's own baseline psychological distress and psychological characteristics were important in the prediction of later psychological distress among both individuals with SCI or ABI and their significant others. Screening based on these variables could help to identify persons at risk for psychological distress. (C) 2020 by the American Congress of Rehabilitation Medicine</p

Trajectories of Self-Efficacy, Depressed Mood, and Anxiety From Admission to Spinal Cord Injury Rehabilitation to 1 Year After Discharge

OBJECTIVE: Self-efficacy (SE) is an important determinant for the psychological adjustment of people with spinal cord injury (SCI). However, little is known about the course of SE during inpatient rehabilitation up to 1 year after discharge. The aim of this study was to determine latent trajectory classes of SE, depressive mood, and anxiety in people with SCI, as well as the interrelationships between these trajectories. DESIGN: Longitudinal inception cohort study. SETTING: Eight specialized SCI rehabilitation centers. PARTICIPANTS: The participants (N=268) were mainly men 183 of 268 (68.3%) with a mean age of 55.6 years. Almost half had a traumatic SCI 135 of 268 (50.4%) and tetraplegia (53.7%), and the minority had a motor complete SCI (32.2%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SE was measured using the University of Washington Self-Efficacy Scale. In addition, the Hospital Anxiety and Depression Scale was used to asses distress and perform dual trajectory modeling analyses. RESULTS: Three trajectories of SE, indicating low, middle, and high SE, could be distinguished. Furthermore, a 2-class trajectory solution for depressive mood and a 4-class solution for anxiety were found to be most suitable. All trajectories were stable over time. Developmental connections between SE and depressive mood and between SE and anxiety were revealed. In particular, participants who adjusted well, reporting low scores on depressive mood and anxiety, could be identified by their high SE scores. However, the group of participants with high depressive mood scores and anxiety scores could not always be identified based on their SE trajectory. CONCLUSIONS: In accordance with our hypotheses, distinct trajectories of SE, depressive mood, and anxiety were identified and high probabilities that SE trajectories were interrelated to the trajectories from depressive mood and anxiety were confirmed. Concurrent screening for SE and distress might best detect people at risk for adjustment problems

Detection and Plant Monitoring Programs: Lessons from an Intensive Survey of Asclepias meadii with Five Observers

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Monitoring programs, where numbers of individuals are followed through time, are central to conservation. Although incomplete detection is expected with wildlife surveys, this topic is rarely considered with plants. However, if plants are missed in surveys, raw count data can lead to biased estimates of population abundance and vital rates. To illustrate, we had five independent observers survey patches of the rare plant Asclepias meadii at two prairie sites. We analyzed data with two mark-recapture approaches. Using the program CAPTURE, the estimated number of patches equaled the detected number for a burned site, but exceeded detected numbers by 28% for an unburned site. Analyses of detected patches using Huggins models revealed important effects of observer, patch state (flowering/nonflowering), and patch size (number of stems) on probabilities of detection. Although some results were expected (i.e. greater detection of flowering than nonflowering patches), the importance of our approach is the ability to quantify the magnitude of detection problems. We also evaluated the degree to which increased observer numbers improved detection: smaller groups (3–4 observers) generally found 90 – 99% of the patches found by all five people, but pairs of observers or single observers had high error and detection depended on which individuals were involved. We conclude that an intensive study at the start of a long-term monitoring study provides essential information about probabilities of detection and what factors cause plants to be missed. This information can guide development of monitoring programs

Use of probiotics in preventing antibiotic associated diarrhoea and Clostridium difficile associated diarrhoea in spinal injury centres: An international survey of four western European countries

Probiotics may prevent antibiotic-associatedand Clostridium difficile-associated- diarrhoea (AAD/CDAD). Many spinal cord injury centres (SCICs) practitioners consider probiotics generically and may not realise that efficacy can be strain-, dose-, and disease-specific. One to four SCICs per country (depending on population size) were contacted (UK:4; the Netherlands:3; Belgium: I; Republic of Ireland: 1) to (a) determine if they stocked probiotics; (b) determine whether the use of those probiotics was evidence-based; and (c) document their C. difficile infection (CDI) practices. All nine SCICs responded to the survey (7 physicians, 3 microbiologists, 1 nurse and 2 dietitians). Five (55.5%) stocked probiotics; five different probiotics were identified. Four probiotics were preferred choice prevention o f AAD/CDAD were Lactobacillus casei Shirota (44.4%), L. casei D N -114001 (22.2%), L. acidophilus (22.2%) and a mixed-strains probiotic (Ecologic Pro-AD) (11.1%). Only one evidence base study was identified supporting the use of probiotic for prevention of AAD in SCI patients. Mean CDI cases per 10,000 patient-days were 0.307 (s.d: 0.486, range 0.00 to 1.08). Definitions of diarrhoea and CDI varied among SCICs. Stocking probiotics for the prevention of AAD / CDAD is not common. There is only one single study showing efficiency of a particular strain in SCI populations. The study highlighted the importance of using a standardised definition o f diarrhoea when conducting AAD/CDAD research

International Comparison of Vocational Rehabilitation for Persons With Spinal Cord Injury:Systems, Practices, and Barriers

Background: Employment rates among people with spinal cord injury or spinal cord disease (SCI/D) show considerable variation across countries. One factor to explain this variation is differences in vocational rehabilitation (VR) systems. International comparative studies on VR however are nonexistent. Objectives: To describe and compare VR systems and practices and barriers for return to work in the rehabilitation of persons with SCI/D in multiple countries. Methods: A survey including clinical case examples was developed and completed by medical and VR experts from SCI/D rehabilitation centers in seven countries between April and August 2017. Results: Location (rehabilitation center vs community), timing (around admission, toward discharge, or after discharge from clinical rehabilitation), and funding (eg, insurance, rehabilitation center, employer, or community) of VR practices differ. Social security services vary greatly. The age and preinjury occupation of the patient influences the content of VR in some countries. Barriers encountered during VR were similar. No participant mentioned lack of interest in VR among team members as a barrier, but all mentioned lack of education of the team on VR as a barrier. Other frequently mentioned barriers were fatigue of the patient (86%), lack of confidence of the patient in his/her ability to work (86%), a gap in the team's knowledge of business/legal aspects (86%), and inadequate transportation/accessibility (86%). Conclusion: VR systems and practices, but not barriers, differ among centers. The variability in VR systems and social security services should be considered when comparing VR study results