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Growers desire more techniques to control weeds in horticultural crops that are grown organically and consumed directly, such as red raspberry. Abrasive grit emited via high air pressure is a new method for controlling weeds. Grit derived from corn cobs was examined for its efficacy during the year of raspberry establishment for two to three years at three sites (seven site-years) and compared with efficacy of hand-weeding as well as no weed control. Grit was applied once or twice weekly after raspberry transplantation in spring until weed emergence ceased in mid to late July. Weeds and raspberry growth were assessed in August. Grit was effective in controlling broadleaf weeds, averaging 94% control across site-years, but control of grass weeds was <10%. Total weed (broadleaf plus grass) control across site-years ranged from 51 to 96% and averaged 78%. Raspberry cane growth was affected by weeds, and grit-weeding at least partially alleviated these effects. Thus, abrasive grit allows growers to manage broadleaf weeds effectively without herbicides or soil tillage. However, additional research is needed to determine the correct amounts and timing of grit applications, as well as more efficacious types of grit, to control grass weeds.
Several studies show, that there exist different diagnosed psychological concomitant diseases with internet addiction. In order to point out the different kinds and frequentness of comorbidities with Internet addiction the Anton Proksch Institut Vienna and the University Mainz - Ambulanz für Spielsucht started a combined, compareable research project, which should show the similarities and differences of comorbidities of the interned addicted patients of both institutions.
In order to become comparable results of both Institutes, the same inquiry methods were used. For the diagnostic of Internet addiction the Scale for the Assessment of Computergame-Addiction (ACA-S), developed by the university medical center of Mainz, is used. In order to be able to cover a broad spectrum on possibly arising concomitant diseases, standardised surveytools are used from different, relevant areas of application. Therefore the Adult Attachement Scale (AAS), the Cambridge Depersonalisation Scale (CDS-9), the d2 (Test of attention), the subscale “Social Insecurity” of EDI-2 (Eating Disorder Inventory-2), the Liebowitz Social Anxiety Scale (LSAS), the NEO Five Factors Inventory (NEO-FFI), the Symptom Checklist 90R (SCL 90-R), the Sensation Seeking Scale V (SSS-V) and the Wender Utah Rating Scale (WURS-k) were used.
First current results of the investigation of comorbidities with internet addiction show a frequent arise of social anxiety, depression and attention deficit hyperactivity disorder (ADHD), which are in both samples remarkably.
The study illustrates, that the patients, which suffer from internet addiction disorder, often show comorbidities, which should be considered in the therapeutic work with Internet-addicted patients.
Cholesterol 24S-hydroxylase (CYP46) catalyzes the conversion of cholesterol to 24S-hydroxycholesterol, the primary cerebral cholesterol elimination product. Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer’s disease (AD) and results are contradictory.
We performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.
Two of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p = 0.016; rs4900442: p = 0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p = 0.006). Haplotypes including both SNPs were calculated and haplotype G–C was identified to influence the risk of AD (p = 0.005). AD patients and non-demented controls, who were carriers of the G–C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p = 0.001) and cholesterol (p < 0.001).
Our results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.
Pathological gambling accumulates frequently in connection with other diseases. This is documented both by studies and clinical observations, whereby no causalities can be derived, which underlying disease led to further diseases. Nevertheless different studies show similar results that pathological gambling arises increased in connection with substance dependence, depressive disorders, obsessive compulsive disorders and also personality disorders. These results stated in the literature also reflect the clinical observations of the Anton Proksch Institute.
In the following presentation we will try to figure out the results of inpatients with the diagnosis pathological gambling, that were treated in the Anton Proksch Institute in the years 2008, 2009 and 2010. We find a range of comorbititys longing from substance abuse to personality disorders.
Inappropriate subjects may be enrolled in a study when enrollment pressures cause inflated baseline severity scores. An increasing number of studies now include methods such as blinded independent centralized ratings (CR) to ensure that appropriate subjects are entered into the trial. Post-baseline factors such as functional unblinding, expectation bias and rater drift can also affect outcomes.
Independent raters, blind to study visit, can minimize functional unblinding and expectation bias. Continuous calibration of CR can minimize rater drift.
To examine studies with both site ratings (SR) and CR to determine how critical post-baseline blinding and continuous calibration are.
A trial of acute schizophrenia used CR for the PANSS and SR for the BPRS on the same subjects.
A Parkinson's psychosis study used CR in the US and SR ex-US to assess subjects using the SAPS.
A GAD trial used CR of subjects enrolled by SRs’ SIGH-A evaluations.
In the schizophrenia trial, CR separated the active comparator and one of two test arms. SR separated the active comparator but neither test arm.
In the Parkinson's psychosis study, pimavanserin showed greater separation with CR than SR.
In the GAD trial, CR had lower placebo response than SR, independent of subject selection.
Data from several studies support the continued importance of rater blinding and independence, post subject selection. Results suggest that precision of ratings beyond baseline can increase the sensitivity of findings in a clinical trial, decrease placebo response rates and potentially eliminate Type II errors.
NMDA receptor ligands have been shown to rapidly treat depression but are associated with psychotomimetic effects. GLYX-13 is an NMDA receptor glycine site functional partial agonist with ~ 25% of the agonist activity of glycine or Dserine. Animal models suggest a single intravenous dose may produce long-term efficacy without psychotomimetic effects.
A phase II randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy of GLYX-13 with central raters.
To examine the effects of a single dose of GLYX-13 in subjects with inadequate response to previous treatment for MDD.
48 male and 68 female subjects received a single dose of GLYX-13 (1-/5-/10-/30-mg/kg) or placebo. Central raters assessed subjects via telephone using the HDRS-17 at Screening, Baseline, Days 1, 3, 7, 14, 21 and 28.
The a priori primary efficacy ANCOVA on pooled drug dose versus placebo was not significant for change from baseline to Day 1 on HDRS-17 total score. MMRM revealed a statistically significant reduction in HDRS-17 total score versus placebo at Day 3 for 5-mg/kg (−4.4; p < .05) and a trend at Day 1 for 5-mg/kg (−3.5; p = .068) and at Day 7 for 5 and 10-mg/kg (−4.0 for both; p's = .059 and .073). GLYX-13 did not cause psychotomimetic side effects at any dose studied.
This study suggests that GLYX-13, an NMDA receptor glycine site functional partial agonist, rapidly reduces depression scores without eliciting psychotomimetic effects at therapeutic doses as assessed by central raters. Further study is indicated.
Negative syndromes in Schizophrenia are of increasing interest to drug developers. Several assessment strategies have emerged for identifying negative symptoms including the NSA-16, PANSS negative symptom subscale and the Marder subscale. Assessment of patients with schizophrenia by videoconferencing has been shown to yield results equivalent to those obtained when the scale is administered face-to-face.
To assess remote assessment of negative symptoms including blinding to protocol details and visit number, effectively eliminating enrollment and expectation biases.
To assess whether negative symptom scales can be reliably assessed in a clinical trial by videoconferencing.
The PANSS and the NSA-16 were administered to 227 subjects with schizophrenia in a randomized clinical trial via live videoconferencing by 17 blinded independent central raters. Subjects were interviewed at screen, at 11 more visits over 36 weeks, and at endpoint or 1 year. On a subset of subjects, a senior clinician observed and independently rated the PANSS and NSA as a quality control measure.
ICCs between raters and observing trainers were .98 on the NSA total score (N = 65 pairs) and .96 on the PANSS total score (N = 69 pairs). ICCs of individual NSA items ranged from .72-1.0, with a mean ICC of .91. ICCs of PANSS subscales ranged from .94 -.96 with ICCs of .95 for the Marder subscale and .94 for the negative subscale.
Excellent item-level ICCs for the NSA suggest that negative symptoms can be rated reliably by videoconferencing using well-calibrated blinded independent raters.
Centralized ratings by telephone have proven feasible for assessment of psychiatric diagnosis, symptom severity, and suicidality, and may be used for safety assessments in non-psychiatric trials with sites that do not employ staff experienced in psychiatric assessment.
To assess whether centralizing assessments with mental health experts enables immediate clinical follow-up and actionable diagnostic support for investigators.
To examine the feasibility of centralized ratings in a Phase III dermatology clinical trial for safety assessments.
1127 subjects enrolled in a trial of medication for their dermatologic condition were assessed via telephone by central raters who administered the SCID-CT, C-SSRS and PHQ-8 at screening. At monthly visits, central raters performed the C-SSRS, PHQ-8, GAD-7 and items designed to detect emergent psychotic symptoms.
34 subjects were excluded on the basis of SCID-CT diagnosis. Based on diagnosis or severity, subjects were classified as being in no need of mental health services, having mild psychiatric symptoms (referred to local mental health service provider; n=33), moderate (immediate referral for psychiatric evaluation; n=17), or severe (immediate escort to emergency room; n=0).
One subject reported suicidal ideation on the C-SSRS, 10 reported self-injurious behavior, and 5 reported suicidal behavior in the last year.
No subjects reported suicidal ideation or behavior at any of the 6861 follow-up assessments. One subject reported self-injurious behavior and two reported emergent psychotic symptoms.
This study established the feasibility and acceptability of routine screening and monitoring of psychopathology and suicidality by central raters in a non-psychiatric population.
Expectation bias (EB) occurs when an individual's expectations about an outcome influence perceptions of one's own or others’ behavior. in clinical trials, both raters and subjects may enter trials with expectations. Rater EB occurs when raters expect that subjects will improve over the course of the trial. Subject EB occurs when subjects themselves expect to get better. Rater and subject expectations can interact to create a therapeutic alliance.
To examine the impact of EB on placebo response and drug-placebo separation.
To identify methods for avoiding expectation bias in CNS clinical trials.
We review eight studies that illustrate the problem of rater and subject EB across therapeutic areas.
Studies examining rater EB suggest it can affect diagnosis and decrease IRR when subjects do not behave according to expectations. Studies of subject EB suggest subject expectations can increase placebo response and affect study outcome. Studies of the interaction of rater and subject expectations find placebo response increases with number of follow-up visits, and having a different rater for baseline, endpoint, and sequential visits may decrease placebo response.
Patient expectations, rater expectations, and rater-patient relationships can increase placebo response and decrease signal detection. Blinding raters to protocol details, including entry criteria and visit number, reduces expectations of improvement. Using different raters at baseline, endpoint and consecutive visits reduces the possibility that relationship bias could influence ratings. Utilizing remote, independent raters is one means to adequately blind and vary raters.
To date, psychosocial outcomes after facial transplantation are promising although long-term consequences, outcome of blind patients and the impact on family members are less well investigated. The aim of this study was to examine the long-term psychosocial of a blind patient and his partner 2 and 3 years after facial transplantation.
Depressive and anxiety symptoms, hopelessness, coping, resilience, illness cognitions, marital support, dyadic adjustment, family functioning and quality of life of the patient and the partner were assessed before and 2 and 3 years after transplantation. Reliable change index (RCI) was further calculated to evaluate the magnitude of change.
Most psychological, marital and family scores of both the patient and the partner remained within a normative and healthy range at follow-up. Resilience (RCI: 2.5 & 3.4 respectively), affective responsiveness (RCI: −4.1 & −3.2 respectively), physical quality of life (RCI: 8.7 & 7.2 respectively) and helplessness (RCI: −2.2 & −2.9 respectively) of the patient improved at 2 and 3 years follow-up. Further, dyadic cohesion (RCI: 2.4) of the patient improved at 2 years whereas marital depth (RCI: −2.0) of the partner decreased at 3 years.
The results of this study point to positive long-term psychosocial outcomes of a blind patient and his partner after facial transplantation. Further, they may underscore the importance of patient selection, social support and involvement of family members in treatment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Specific changes in personality profiles may represent early symptoms of Alzheimer's disease (AD). Knowledge about relationship between personality changes and biomarkers of cerebral pathology can contribute to early diagnosis of AD.
To investigate to what extent the personality changes predict the cerebral AD pathology.
To describe the relationship between the personality changes and pathological cerebro-spinal fluid (CSF) biomarkers.
One hundred and ten subjects, of whom 57 patients with mild cognitive impairment (MCI), 9 subjects with mild dementia, and 44 healthy controls had an extensive medical and neuropsychological examination as well as lumbar puncture to evaluate concentrations of CSF biomarkers of AD pathology [amyloid-β1-42 (Aβ1-42), phosphorylated tau (ptau-181), and total-tau (tau)]. The proxies of the participants completed the Revised NEO Personality Inventory (NEO-PI-R) to assess subjects’ personality at the time being and 5 years retrospectively.
In a hierarchical multivariate regression analysis, including age, gender, education, Mini Mental State Examination (MMSE), and APOEe4 status, lower Aβ1-42 concentrations in CSF were associated with increasing neuroticism, and decreasing extraversion and conscientiousness. Decreasing extraversion, openness to experience and conscientiousness were associated with higher tau/Aβ1-42 ratio, and higher ptau-181/Aβ1-42 ratio was related to decreasing extraversion. Personality changes in the domain of agreeableness did not yield any significant effect as a predictor on any of CSF biomarkers.
Our findings suggest that early and specific changes in personality traits are associated with cerebral AD pathology, in particular with amyloid pathology, and may serve as clinical signs to consider when evaluating MCI and mild dementia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis. Many studies highlighted the possible deleterious effects of elevated cortisol on cognition, assuming a likely role of stressful events. Yet, very few studies actually examined these assumed links between life events, cortisol and cognition.
To examine associations between salivary cortisol, cognition and life events in a population of non-demented old individuals.
A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study involving 6733 Lausanne residents. Salivary cortisol samples (upon waking, 30 minutes after waking, at 11 am and at 8 pm) were obtained from 799 non-demented participants aged at least 60.
Life events, activities of daily life along with depressive symptoms were assessed using a standardized questionnaire. A comprehensive neuropsychological test battery was used to determine the Clinical Dementia Rating (CDR).
For multiple comparisons, P values were adjusted (P′) according to Holm-Bonferroni's method.
Cortisol at 11 am and cortisol area under the curve (AUC) were positively correlated with CDR sum of boxes (CDRSOB) scores (P′ = 0.035; Rho = 0.097 and P′ = 0.024; Rho = 0.110, respectively). The association between cortisol AUC and CDRSOB remained significant after controlling for age, sex, body mass index, education, smoking and depression (P = 0.001; β = 0.001; R2 change = 0.016).
The number and the total impact of life events were associated neither with cortisol nor with CDRSOB.
Elevated cortisol was associated with poorer cognitive functioning yet independently of life events. This suggests that the increased cortisol associated with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Using both multivariate regression and artificial neural networks, the relative impact of variables affecting cow-calf profitability was examined over two cattle cycles for spring- and fall-calving herds that varied in size by time period analyzed when using different fertility management affecting forage yields with and without weather uncertainty. Neural networks had greater predictive accuracy than regression but at the cost of lesser transparency and predictive consistency. Explaining profitability, price, and quantity of cattle sold were consistently and respectively ranked first and second using both approaches. Importance rankings for hay sold and fertilizer were low and less consistent across techniques employed.
Behaviour that challenges in people with intellectual disability is associated with higher healthcare, social care and societal costs. Although behavioural therapies are widely used, there is limited evidence regarding the cost and quality-adjusted life-years (QALYs).
We aimed to assess the incremental cost per QALY gained of therapist training in positive behaviour support (PBS) and treatment as usual (TAU) compared with TAU using data from a cluster randomised controlled trial (Clinical Trials.gov registration: NCT01680276).
We conducted a cost-utility analysis (cost per QALY gained) of 23 teams randomised to PBS or TAU, with a total of 246 participants followed up over 36 months. The primary analysis was from a healthcare cost perspective with a secondary analysis from a societal cost perspective.
Over 36 months the intervention resulted in an additional 0.175 QALYs (discounted and adjusted 95% CI −0.068 to 0.418). The total cost of training in and delivery of PBS is £1598 per participant plus an additional cost of healthcare of £399 (discounted and adjusted 95% CI −603 to 1724). From a healthcare cost perspective there is an 85% probability that the intervention is cost-effective compared with TAU at a £30 000 willingness to pay for a QALY threshold.
There was a high probability that training in PBS is cost-effective as the cost of training and delivery of PBS is balanced out by modest improvements in quality of life. However, staff training in PBS is not supported given we found no evidence for clinical effectiveness.
There is widespread concern among scholars, court actors, and policy makers that the number of pro se litigants is increasing. However, we have little empirical evidence of the scope of pro se litigation, especially in the federal court system. Using data from the Administrative Office of the U.S. Courts on all civil case filings since 1999, we investigate the prevalence and rate of pro se litigation in federal district courts. We find no evidence of a dramatic rise in pro se litigation, but we document substantial variation in rates of pro se litigation by type of case and circuit of filing. The results have implications for our understanding of self-representation and for the development of policies addressing access to civil justice.