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Prenatal exposure to persistent organic pollutants and cognition and motor performance in adolescence.

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Prenatal exposure to persistent organic pollutants and cognition and motor performance in adolescence.

Environ Int. 2018 Aug 29;121(Pt 1):13-22

Authors: Berghuis SA, Van Braeckel KNJA, Sauer PJJ, Bos AF

Abstract
BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), was found to be associated with poorer neurological development in children. Knowledge about the effects on outcomes until adolescence is limited.
OBJECTIVES: To determine whether prenatal exposure to POPs, particularly hydroxylated PCBs (OH-PCBs), is associated with cognitive and motor development in 13- to 15-year-old children.
METHODS: This prospective observational cohort study is part of the Development at Adolescence and Chemical Exposure (DACE)-study, a follow-up of two Dutch birth cohorts. Maternal pregnancy serum levels of PCB-153 and three OH-PCBs were measured, in part of the cohort also nine other PCBs and three OH-PCBs, and in another part five polybrominated diphenyl ethers (PBDEs), dichloroethene (DDE), pentachlorophenol (PCP) and hexabroomcyclododecane (HBCDD). Of the 188 invited adolescents, 101 (53.7%) participated, 55 were boys. Cognition (intelligence, attention, verbal memory) and motor performance (fine motor, ball skills, balance) were assessed. Scores were classified into ‘normal’ (IQ > 85; scores > P15) and ‘(sub)clinical’ (IQ ≤ 85; scores ≤ P15). We used linear and logistic regression analyses, and adjusted for maternal education, maternal smoking, maternal alcohol use, breast feeding, and age at examination.
RESULTS: Several OH-PCBs were associated with more optimal sustained attention and balance. PCB-183 was associated with lower total intelligence (OR: 1.29; 95%CI:0.99-1.68; P = .060), and HBCDD with lower performance intelligence (OR: 3.62; 95%CI:0.97-13.49; P = .056). PCBs, OH-PCBs and PBDEs were negatively associated with verbal memory.
CONCLUSIONS: Prenatal background exposure to several POPs can influence neuropsychological outcomes in 13- to 15-year-old Dutch adolescents, although exposure to most compounds does not have clinically relevant consequences at adolescence.

PMID: 30172231 [PubMed – as supplied by publisher]

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High-resolution analysis of the pneumococcal transcriptome under a wide range of infection-relevant conditions.

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High-resolution analysis of the pneumococcal transcriptome under a wide range of infection-relevant conditions.
Nucleic Acids Res. 2018 Aug 27;:
Authors: Aprianto R, Slager J, Holsappel S, Veening JW
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Catalytic regio- and enantioselective alkylation of conjugated dienyl amides.

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Catalytic regio- and enantioselective alkylation of conjugated dienyl amides.
Angew Chem Int Ed Engl. 2018 Aug 24;:
Authors: Harutyunyan SR, Guo Y, Kootstra J
Abstract
We have develop… Continue reading

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Psychological morbidity and general health among family caregivers during end-of-life cancer care: A retrospective census survey.

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Psychological morbidity and general health among family caregivers during end-of-life cancer care: A retrospective census survey.

Palliat Med. 2018 Aug 21;:269216318793286

Authors: Grande G, Rowland C, van den Berg B, Hanratty B

Abstract
BACKGROUND: Family carers provide vital support for patients towards end-of-life, but caregiving has considerable impact on carers’ own health. The scale of this problem is unknown, as previous research has involved unrepresentative samples or failed to fully capture caregiving close to death.
AIM: To quantify level of psychological morbidity and general health among a census sample of carers of people with cancer at end-of-life, compared to population reference data.
DESIGN: National 4-month post-bereavement postal census survey of family carers of people who died from cancer, retrospectively measuring carers’ psychological health (General Health Questionnaire-12) and general health (EuroQoL EQ-Visual Analogue Scale) during the patient’s last 3 months of life.
PARTICIPANTS: N = 1504 (28.5%) of all 5271 people who registered the death of a relative from cancer in England during 2 weeks in 2015 compared with data from the Health Survey for England 2014 ( N = 6477-6790).
RESULTS: Psychological morbidity at clinically significant levels (General Health Questionnaire-12 ⩾4) was substantially higher among carers than the general population (83% vs 15%), with prevalence five to seven times higher across all age groups. Overall, carers’ general health scores were lower than population scores, median 75 (interquartile range, 50-80) versus 80 (interquartile range, 70-90), but differences were more marked at younger ages. Female carers had worse psychological morbidity and general health than male carers.
CONCLUSION: Levels of psychological morbidity among family carers during end-of-life caregiving are far higher than indicated by previous research, indicating a substantial public health problem. Consistent assessment and support for carers to prevent breakdown in caregiving may produce cost savings in long term.

PMID: 30130458 [PubMed – as supplied by publisher]

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New European privacy regulation: Assessing the impact for digital medicine innovations.

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New European privacy regulation: Assessing the impact for digital medicine innovations.
Eur Psychiatry. 2018 Aug 16;54:57-58
Authors: Mulder T, Jagesar RR, Klingenberg AM, P Mifsud Bonnici J, Kas MJ
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Authors’ Response to Braillon’s Comment on: “Limited Evidence for Risk Factors for Proarrhythmia and Sudden Cardiac Death in Patients Using Antidepressants: Dutch Consensus on ECG Monitoring”.

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Authors’ Response to Braillon’s Comment on: “Limited Evidence for Risk Factors for Proarrhythmia and Sudden Cardiac Death in Patients Using Antidepressants: Dutch Consensus on ECG Monitoring”.

Drug Saf. 2018 Aug 17;:

Authors: Simoons M, Seldenrijk A, Mulder H, van Roon E, Bakker R, Ruhé H

PMID: 30120740 [PubMed – as supplied by publisher]

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A design for external quality assessment for the analysis of thiopurine drugs: pitfalls and opportunities.

A design for external quality assessment for the analysis of thiopurine drugs: pitfalls and opportunities.
Clin Chem Lab Med. 2018 Aug 15;:
Authors: Robijns K, van Luin M, Jansen RTP, Neef C, Touw DJ
PMID: 30… Continue reading

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The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: A meta-analysis.

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The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: A meta-analysis.

Schizophr Res. 2018 Aug 07;:

Authors: Prikken M, Konings MJ, Lei WU, Begemann MJH, Sommer IEC

Abstract
BACKGROUND: Computerized methods for improving cognitive functioning in schizophrenia have gained popularity during the past decades. Therefore, this study evaluates the available evidence for the efficacy of computerized cognitive drill and practice training for patients with schizophrenia-spectrum disorders.
METHODS: A systematic search was carried out using PubMed, Embase, Cochrane Database of Systematic Reviews, and PsycINFO. A meta-analysis was performed to compare cognitive drill and practice training in patients with a schizophrenia-spectrum disorder with non-cognitively oriented control conditions. The primary outcome was cognitive functioning. Secondary outcome measures included psychotic symptoms, depressive symptoms, and functional outcomes. Effect sizes (ES) for all included studies were calculated as Hedges’ g.
RESULTS: 24 studies were included with 1262 patients in total. Compared to a control condition, patients receiving computerized cognitive drill and practice training showed significantly more improvement on attention (ES = 0.31, p = 0.001), working memory (ES = 0.38, p < 0.001), positive symptoms (ES = 0.31, p = 0.003), and depressive symptoms (ES = 0.37, p = 0.002). Small, marginally significant effect sizes were found for processing speed, verbal and visual learning and memory, and verbal fluency. However, significant effects on functional outcomes and social cognition were absent.
DISCUSSION: The current study showed evidence for the efficacy of computerized cognitive drill and practice training in patients with schizophrenia-spectrum disorders. However, the absence of effects on social cognition and functional outcomes questions the generalization of treatment effects. Together, these results stimulate further development of computerized training programs for schizophrenia that not only improve cognitive functioning, but also generalize cognitive improvement to functional outcomes.

PMID: 30097278 [PubMed – as supplied by publisher]

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A novel in vitro assay reveals SNARE topology and the role of Ykt6 in autophagosome fusion with vacuoles.

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A novel in vitro assay reveals SNARE topology and the role of Ykt6 in autophagosome fusion with vacuoles.
J Cell Biol. 2018 Aug 10;:
Authors: Gao J, Reggiori F, Ungermann C
Abstract
Au… Continue reading

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Clinical benefit of controversial first line systemic therapies for advanced stage ovarian cancer – ESMO-MCBS scores.

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Clinical benefit of controversial first line systemic therapies for advanced stage ovarian cancer – ESMO-MCBS scores.

Cancer Treat Rev. 2018 Jun 18;69:233-242

Authors: Broekman KE, Jalving M, van Tinteren H, Sessa C, Reyners AKL

Abstract
BACKGROUND: The magnitude of clinical benefit scale (MCBS) was introduced by the European Society of Medical Oncology (ESMO) to quantify the clinical benefit of therapeutic regimens and to prioritise therapies. It distinguishes curative from palliative treatments and ranks their benefit based on overall survival (OS), progression free survival (PFS), quality of life (QoL) and toxicity. Objective of this study on the first line treatment of ovarian cancer was to evaluate the evidence for the current standard of care using the ESMO-MCBSv1.1 with an emphasis on controversial therapeutic options: intraperitoneal chemotherapy, dose-dense paclitaxel and bevacizumab.
METHODS: Phase III trials, published since 1992, investigating first line systemic treatment of Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage IIB-IV epithelial ovarian cancer were included. Since most studies included patients with FIGO stage IV disease or incomplete debulking, all treatments were judged to be palliative. Treatments were graded 5 to 1 on the ESMO-MCBSv1.1, where grades 5 and 4 represent a high level of clinical benefit.
RESULTS: 55 studies met the inclusion criteria. ESMO-MCBS scores were calculated for eleven studies that showed a statistically significant benefit of the experimental treatment. Intraperitoneal (ip) cisplatin scored a 4 and 3, but two other studies were negative and therefore not scored on the ESMO-MCBS. Dose-dense paclitaxel showed substantial clinical benefit in one study (score 4), but three studies were negative. Addition of bevacizumab also scored a 4 in one study subgroup including high-risk patients but a 2 in another trial with a larger study population.
CONCLUSION: Based on ESMO-MCBS scores, dose-dense paclitaxel and intraperitoneal chemotherapy cannot be recommended as standard treatment. Bevacizumab should be considered only in the high-risk population. The ESMO-MCBSv1.1. helps to summarise reported studies on controversial treatment regimens, and identifies their weaknesses.

PMID: 30098485 [PubMed – as supplied by publisher]

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Boosting heterologous protein production yield by adjusting global nitrogen and carbon metabolic regulatory networks in Bacillus subtilis.

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Boosting heterologous protein production yield by adjusting global nitrogen and carbon metabolic regulatory networks in Bacillus subtilis.

Metab Eng. 2018 Aug 07;:

Authors: Cao H, Villatoro-Hernandez J, Weme RDO, Frenzel E, Kuipers OP

Abstract
Bacillus subtilis is extensively applied as a microorganism for the high-level production of heterologous proteins. Traditional strategies for increasing the productivity of this microbial cell factory generally focused on the targeted modification of rate-limiting components or steps. However, the longstanding problems of limited productivity of the expression host, metabolic burden and non-optimal nutrient intake, have not yet been completely solved to achieve significant production-strain improvements. To tackle this problem, we systematically rewired the regulatory networks of the global nitrogen and carbon metabolism by random mutagenesis of the pleiotropic transcriptional regulators CodY and CcpA, to allow for optimal nutrient intake, translating into significantly higher heterologous protein production yields. Using a β-galactosidase expression and screening system and consecutive rounds of mutagenesis, we identified mutant variants of both CodY and CcpA that in conjunction increased production levels up to 290%. RNA-Seq and electrophoretic mobility shift assay (EMSA) showed that amino acid substitutions within the DNA-binding domains altered the overall binding specificity and regulatory activity of the two transcription factors. Consequently, fine-tuning of the central metabolic pathways allowed for enhanced protein production levels. The improved cell factory capacity was further demonstrated by the successfully increased overexpression of GFP, xylanase and a peptidase in the double mutant strain.

PMID: 30096425 [PubMed – as supplied by publisher]

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Vitamin A and beta (β)-carotene supplementation for cystic fibrosis.

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Vitamin A and beta (β)-carotene supplementation for cystic fibrosis.

Cochrane Database Syst Rev. 2018 Aug 09;8:CD006751

Authors: de Vries JJ, Chang AB, Bonifant CM, Shevill E, Marchant JM

Abstract
BACKGROUND: People with cystic fibrosis (CF) and pancreatic insufficiency are at risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A deficiency predominantly causes eye and skin problems, while excessive levels of vitamin A can harm the respiratory and skeletal systems in children and interfere with the metabolism of other fat-soluble vitamins. Most CF centres administer vitamin A as supplements to reduce the frequency of vitamin A deficiency in people with CF and to improve clinical outcomes such as growth, although the recommended dose varies between different guidelines. Thus, a systematic review on vitamin A and vitamin A-like supplementation (carotenes or other retinoids) in people with CF would help guide clinical practice. This is an update of an earlier Cochrane Review.
OBJECTIVES: To determine if supplementation with vitamin A, carotenes or other retinoid supplements in children and adults with CF reduces the frequency of vitamin A deficiency disorders, improves general and respiratory health and affects the frequency of vitamin A toxicity.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. Additionally we searched several ongoing trials registries, including ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number Registry.Most recent database searches: 01 June 2018.
SELECTION CRITERIA: All randomised or quasi-randomised controlled studies comparing all preparations of oral vitamin A, carotenes or retinoids (or in combination), used as a supplement compared to placebo at any dose, for at least three months, in people with CF (diagnosed by sweat tests or genetic testing) with and without pancreatic insufficiency.
DATA COLLECTION AND ANALYSIS: Two authors individually assessed study quality and extracted data on outcome measures. The authors assessed the quality of the evidence using the GRADE system. Investigators were contacted to retrieve missing quantitative data.
MAIN RESULTS: No studies of vitamin A or other retinoid supplementation were eligible for inclusion. However, one randomised study of beta (β)-carotene supplementation involving 24 people with CF who were receiving pancreatic enzyme substitution was included. The study compared successive β-carotene supplementation periods (high dose followed by low dose) compared to placebo. The results for the low-dose supplementation period should be interpreted with caution, due to the lack of a wash-out period after the high-dose supplementation.The included study did not report on two of the review’s primary outcomes (vitamin A deficiency disorders and mortality); results for our third primary outcome of growth and nutritional status (reported as z score for height) showed no difference between supplementation and placebo, mean difference (MD) -0.23 (95% confidence interval (CI) -0.89 to 0.43) (low-quality evidence). With regards to secondary outcomes, supplementation with high-dose β-carotene for three months led to significantly fewer days of systemic antibiotics required to treat pulmonary exacerbations, compared to controls, MD -15 days (95% CI -27.60 to -2.40); however, this was not maintained in the second three-month section of the study when the level of β-carotene supplementation was reduced, MD -8 days (95% CI -18.80 to 2.80) (low-quality evidence). There were no statistically significant effects between groups in lung function (low-quality evidence) and no adverse events were observed (low-quality evidence). Supplementation affected levels of β-carotene in plasma, but not vitamin A levels. The study did not report on quality of life or toxicity.
AUTHORS’ CONCLUSIONS: Since no randomised or quasi-randomised controlled studies on retinoid supplementation were identified, no conclusion on the supplementation of vitamin A in people with CF can be drawn. Additionally, due to methodological limitations in the included study, also reflected in the low-quality evidence judged following the specific evidence grading system (GRADE), no clear conclusions on β-carotene supplementation can be drawn. Until further data are available, country- or region-specific guidelines regarding these practices should be followed.

PMID: 30091146 [PubMed – as supplied by publisher]

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Reaction to “Intergrating smoking cessation care in alcohol and other drug treatment settings using an organisational change intervention: a systematic review” by Skelton, et al.

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Reaction to “Intergrating smoking cessation care in alcohol and other drug treatment settings using an organisational change intervention: a systematic review” by Skelton, et al.
Addiction. 2018 Aug 09;:
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Clinical outcome and risk factors for failure in late acute prosthetic joint infections treated with debridement and implant retention.

Clinical outcome and risk factors for failure in late acute prosthetic joint infections treated with debridement and implant retention.

J Infect. 2018 Aug 06;:

Authors: Wouthuyzen-Bakker M, Sebillotte M, Lomas J, Taylor A, Palomares EB, Murillo O, Parvizi J, Shohat N, Reinoso JC, Sánchez RE, Fernandez-Sampedro M, Senneville E, Huotari K, Allende JMB, Garcia-Cañete J, Lora-Tamayo J, Ferrari MC, Vaznaisiene D, Yusuf E, Aboltins C, Trebse R, Salles MJ, Benito N, Vila A, Toro MDD, Kramer TS, Petersdorf S, Diaz-Brito V, Tufan ZK, Sanchez M, Arvieux C, Soriano A, ESCMID Study Group for Implant-Associated Infections (ESGIAI)

Abstract
OBJECTIVES: Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI), but its efficacy in patients with late acute (LA) PJI is not well described.
METHODS: Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively evaluated. LA PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: i) the need for implant removal, ii) infection related death, iii) the need for suppressive antibiotic therapy and/or iv) relapse or reinfection during follow-up.
RESULTS: 340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Significant independent preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein >150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35).
CONCLUSION: LA PJIs have a high failure rate. Treatment strategies should be individualized according to patients’ age, comorbidity, clinical presentation and microorganism causing the infection.

PMID: 30092305 [PubMed – as supplied by publisher]

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Single-chain polymer nanoparticles in controlled drug delivery and targeted imaging.

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Single-chain polymer nanoparticles in controlled drug delivery and targeted imaging.

J Control Release. 2018 Aug 02;:

Authors: Kröger APP, Paulusse JMJ

Abstract
As a relatively new class of materials, single-chain polymer nanoparticles (SCNPs) just entered the field of (biomedical) applications, with recent advances in polymer science enabling the formation of bio-inspired nanosized architectures. Exclusive intramolecular collapse of individual polymer chains results in individual nanoparticles. With sizes an order of magnitude smaller than conventional polymer nanoparticles, SCNPs are in the size regime of many proteins and viruses (1-20 nm). Multifaceted syntheses and design strategies give access to a wide set of highly modular SCNP materials. This review describes how SCNPs have been rendered water-soluble and highlights ongoing research efforts towards biocompatible SCNPs with tunable properties for controlled drug delivery, targeted imaging and protein mimicry.

PMID: 30077737 [PubMed – as supplied by publisher]

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Substance use disorders and sexual behavior; the effects of alcohol and drugs on patients’ sexual thoughts, feelings and behavior.

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Substance use disorders and sexual behavior; the effects of alcohol and drugs on patients’ sexual thoughts, feelings and behavior.
Addict Behav. 2018 Jul 06;87:231-237
Authors: Bosma-Bleeker MH, Blaa… Continue reading

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The establishment of hybrids of the Daphnia longispina complex explained by a mathematical model incorporating different overwintering life history strategies.

The establishment of hybrids of the Daphnia longispina complex explained by a mathematical model incorporating different overwintering life history strategies.
PLoS One. 2018;13(7):e0200802
Authors: Griebel J, Utz M,… Continue reading

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Visual Performance as a Function of Luminance in Glaucoma: The De Vries-Rose, Weber’s, and Ferry-Porter’s Law.

Visual Performance as a Function of Luminance in Glaucoma: The De Vries-Rose, Weber’s, and Ferry-Porter’s Law.

Invest Ophthalmol Vis Sci. 2018 Jul 02;59(8):3416-3423

Authors: Bierings RAJM, de Boer MH, Jansonius NM

Abstract
Purpose: To determine whether the De Vries-Rose, Weber’s, and Ferry-Porter’s law, which describe visual performance as a function of luminance, also hold in patients with glaucoma.
Methods: A case-control study with 19 glaucoma patients and 45 controls, all with normal visual acuity. We measured foveal and peripheral contrast sensitivity (CS) using static perimetry and foveal and peripheral critical fusion frequency (CFF; stimulus diameter 1°) as a function of luminance (0.02 to 200 cd/m2). ANOVA was used to analyze the effect of glaucoma and luminance on CS and CFF; analyses were adjusted for age and sex.
Results: Foveally, logCS was proportional to log luminance at lower luminances (de Vries-Rose) and saturated at higher luminances (Weber); glaucoma patients had a 0.4 log unit lower logCS than controls (P < 0.001), independent of luminance. Peripherally, the difference was more pronounced at lower luminances (P = 0.007). CFF was linearly related to log luminance (Ferry-Porter). Glaucoma patients had a lower CFF compared with controls (P < 0.001), with a smaller slope of the CFF versus log luminance curve, for both the fovea (6.8 vs. 8.7 Hz/log unit; P < 0.001) and the periphery (2.5 vs. 3.4 Hz/log unit; P = 0.012).
Conclusions: Even in apparently intact areas of the visual field, visual performance is worse in glaucoma patients than in healthy subjects for a wide range of luminances, without a clear luminance dependency that is consistent across the various experiments. This indicates impaired signal processing downstream in the retina and beyond, rather than an impaired light adaptation in the strictest sense.

PMID: 30025071 [PubMed – in process]

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Pharmacokinetic Pharmacodynamic Perspective on the Detection of Signs of Neural Inertia in Humans.

Pharmacokinetic Pharmacodynamic Perspective on the Detection of Signs of Neural Inertia in Humans.
Anesthesiology. 2018 Aug;129(2):373-375
Authors: Colin PJ, Kuizenga MH, Vereecke HEM, Struys MMRF
PMID: 30020… Continue reading

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The longitudinal effects of induction on beginning teachers’ stress.

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The longitudinal effects of induction on beginning teachers’ stress.

Br J Educ Psychol. 2018 Jul 11;:

Authors: Harmsen R, Helms-Lorenz M, Maulana R, van Veen K

Abstract
BACKGROUND: Teaching is a stressful profession especially for beginning teachers. Induction programmes can support beginning teachers. Little is known concerning which elements of induction programmes can influence (the change in) teachers’ stress over time.
AIMS: This study aims to investigate the growth of stress causes and stress responses during the first 3 years of professional practice and to reveal the influence of induction arrangement elements on the initial level as well as the change in stress levels over the 2 years that followed.
SAMPLE: Longitudinal data from a sample of 393 beginning teachers (56.5% female) were collected at three measurement occasions. All teachers were offered four different induction arrangement elements.
METHOD: Results of multiple group confirmatory factor analysis confirmed longitudinal measurement invariance. Multivariate latent growth curve modelling (MLGM) was conducted to examine the initial status, the subsequent linear growth, and the influence of the individual induction arrangement elements on the stress causes and stress responses.
RESULTS: MLGM results show that perceived stress caused by high psychological task demands increases over time (d = 0.22), whereas perceived stress caused by negative pupil aspects decreases over time (d = -0.52). Further, workload reduction decreases the level of perceived high psychological task demands, negative social aspects, and all the stress responses. Perceived support for effective teaching behaviour decreases the level of perceived negative emotions and discontent. Further, school enculturation has an influence on the change in perceived discontent over time.
CONCLUSIONS: Perceived stress causes and stress responses can change over time. Specific induction arrangement elements appear to be powerful elements to reduce the level, and the change over time, of specific perceived stress causes and stress responses.

PMID: 29998489 [PubMed – as supplied by publisher]

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