God\u27s Church Is Just: A Specific Discussion Of Some Cases of Church Discipline

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Model-based design of MADIX under bulk and solution conditions

Macromolecular design by interchange of xanthates (MADIX) is a less studied controlled radical polymerization technique from a mechanistic and modeling point of view. In this contribution, MADIX of styrene and chain extension toward the synthesis of block copolymers is investigated, with azobisisobutyronitrile as conventional radical initiator and O-ethylxanthyl ethyl propionate as initial RAFT agent (R0X). Degenerative transfer coefficients for both the exchange with R0X and macro-RAFT agent are reported and their difference is highlighted to be relevant for the kinetic description. The model validity is supported by measurement of end-group functionality (EGF) data considering elemental analysis. Novel mechanistic insights are that in contrast to typical reversible addition fragmentation chain transfer (RAFT) polymerizations the macroradical CLD follows a Schulz-Flory distribution and that both during the homopolymerization and the chain extensions an exchange, so with monomer incorporation, only takes place once [1]. [1] D.J.G. Devlaminck, P.H.M. Van Steenberge, M.-F. Reyniers, D.R. D’hooge, Polym Chem. 2017, 8, 694

DNA methylation as a triage tool for cervical cancer screening - A meeting report.

INTRODUCTION: DNA methylation is proposed as a novel biomarker able to monitor molecular events in human papillomavirus (HPV) infection pathophysiology, enabling the distinction between HPV-induced lesions with regression potential from those that may progress to HPV-related cancer. METHODS: This meeting report summarises the presentations and expert discussions during the HPV Prevention and Control Board-focused topic technical meeting on DNA methylation validation in clinician-collected and self-collected samples, novel DNA methylation markers discovery, implementation in cervical cancer screening programs, and their potential in women living with human immunodeficiency virus (HIV). RESULTS: Data presented in the meeting showed that HPV-positive, baseline methylation-negative women have a lower cumulative cervical cancer incidence than baseline cytology-negative women, making DNA methylation an attractive triage strategy. However, additional standardised data in different settings (low- versus high-income settings), samples (clinician-collected and self-collected), study designs (prospective, modelling, impact) and populations (immunocompetent women, women living with HIV) are needed. CONCLUSION: Establishing international validation guidelines were identified as the way forward towards accurate validation and subsequent implementation in current screening programs

Nitrogen activation in a Mars-van Krevelen mechanism for ammonia synthesis on Co3Mo3N

Co3Mo3N is one of the most active catalysts for ammonia synthesis; however, little is known about the atomistic details of N2 adsorption and activation. Here we examine whether N2 can adsorb and activate at nitrogen surface vacancies. We have identified the most favorable sites for surface nitrogen vacancy formation and have calculated vacancy formation free energies (and concentrations) taking into account vacancy configurational entropy and the entropy of N2 at temperature and pressure conditions relevant to ammonia synthesis (380–550 °C, 100 atm) via a semiempirical approach. We show that 3-fold hollow bound nitrogen-containing (111)-surfaces have surprisingly high concentrations (1.6 × 1016 to 3.7 × 1016 cm–2) of nitrogen vacancies in the temperature range for ammonia synthesis. It is shown that these vacancy sites can adsorb and activate N2 demonstrating the potential of a Mars–van Krevelen type mechanism on Co3Mo3N. The catalytically active surface is one where 3f-hollow-nitrogens are bound to the molybdenum framework with a hexagonal array of embedded Co8 cobalt nanoclusters. We find that the vacancy-formation energy (VFE) combined with the adsorption energy can be used as a descriptor in the screening of materials that activate doubly and triply bonded molecules that are bound end-on at surface vacancies

The relevance of arterial blood pressure in the management of glaucoma progression: a systematic review

Background Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure and ocular perfusion pressure is poorly understood. Objective This systematic review aims to provide clinicians with the latest literature regarding the management of arterial blood pressure in glaucoma patients. Methods A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial blood pressure and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. Results 80 articles were included in this systemic review. A bimodal relation between blood pressure and glaucoma progression was found. Both high and low blood pressure increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the blood pressure over 24-hours. Conclusions We concluded that systemic blood pressure level associates with glaucomatous damage and provided recommendations for the management and study of arterial blood pressure in glaucoma. Prospective clinical trials are needed to further support these recommendations

The influence of distributed leadership on teachers' organizational commitment: a multilevel approach

In the present study the effects of a cooperative leadership team, distributed leadership, participative decision-making, and context variables on teachers' organizational commitment are investigated. Multilevel analyses on data from 1522 teachers indicated that 9% of the variance in teachers' organizational commitment is attributable to differences between schools. The analyses revealed that especially the presence of a cooperative leadership team and the amount of leadership support played a significantly positive key role in predicting teachers' organizational commitment. Also, participative decision-making and distribution of the supportive leadership function had a significant positive impact on teachers' organizational commitment. In contrast, distribution of the supervisory leadership function and teachers' job experience had a significant negative impact

The relation between school leadership from a distributed perspective and teachers' organizational commitment: examining the source of the leadership function

Purpose: In this study the relationship between school leadership and teachers’ organizational commitment is examined by taking into account a distributed leadership perspective. The relation between teachers’ organizational commitment and contextual variables of teachers’ perceptions of the quality and the source of the supportive and supervisory leadership function, participative decision making, and cooperation within the leadership team are examined. Research Design: A survey was set up involving 1,522 teachers from 46 large secondary schools in Flanders (Belgium). Because the data in the present study have an inherent hierarchical structure, that is, teachers are nested into schools, hierarchical linear modeling techniques are applied. Findings: The analyses reveal that 9% of the variance in teachers’ organizational commitment is attributable to differences between schools. Teachers’ organizational commitment is mainly related to quality of the supportive leadership, cooperation within the leadership team, and participative decision making. Who performed the supportive leadership function plays only a marginally significant positive role. The quality of the supervisory leadership function and the role of the leadership team members in this function were not significantly related to teachers’ organizational commitment. Conclusions: The implications of the findings are that to promote teachers’ organizational commitment teachers should feel supported by their leadership team and that this leadership team should be characterized by group cohesion, role clarity, and goal orientedness. Recommendations for further research are provided

Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour

AbstractBackgroundGastrointestinal stromal tumours (GIST) treated with the tyrosine kinase inhibitor (TKI) imatinib can become resistant when additional mutations in the receptor tyrosine kinases KIT or PDGFRA block imatinib activity. Mutated KIT requires the molecular chaperone heat-shock protein 90 (HSP90) to maintain stability and activity. Onalespib (AT13387) is a potent non-ansamycin HSP90 inhibitor. We hypothesised that the combination of onalespib and imatinib may be safe and effective in managing TKI-resistant GIST.Patients and methodsIn this dose-escalation study, we evaluated the safety and efficacy of combination once-weekly intravenous onalespib for 3 weeks and daily oral imatinib in 28-d cycles. Twenty-six patients with TKI-resistant GIST were enrolled into four sequential dose cohorts of onalespib (dose range, 150–220 mg/m2) and imatinib 400 mg. The relationship between tumour mutational status (KIT/PDGFRA) and efficacy of treatment was explored.ResultsCommon onalespib-related adverse events were diarrhoea (58%), nausea (50%), injection site events (46%), vomiting (39%), fatigue (27%), and muscle spasms (23%). Overall, 81% of patients reported more than one onalespib-related gastrointestinal disorder. Nine patients (35%) had a best response of stable disease, including two patients who had KIT mutations known to be associated with resistance to imatinib and sunitinib. Disease control at 4 months was achieved in five patients (19%), and median progression-free survival was 112 d (95% confidence interval 43–165). One patient with PDGFRA-mutant GIST had a partial response for more than 376 d.ConclusionThe combination of onalespib plus imatinib was well tolerated but exhibited limited antitumour activity as dosed in this TKI-resistant GIST patient population.Trial registration ID: clinicaltrials.gov: NCT0129420

Neuropsychological performance in solvent-exposed vehicle collision repair workers in New Zealand?

To assess whether solvent use and workplace practices in the vehicle collision repair industry are associated with symptoms of neurotoxicity in spray painters and panel beaters (auto body repair workers). Neurobehavioural symptoms were assessed using a cross-sectional study design in 370 vehicle collision repair and 211 reference workers using the EUROQUEST questionnaire. Full-shift airborne solvent levels were measured in a subset (n=92) of collision repair workers. Solvent exposures were higher in spray painters than in panel beaters, but levels were below current international exposure standards. Collision repair workers were more likely to report symptoms of neurotoxicity than reference workers with ORs of 2.0, 2.4 and 6.4 (all p<0.05) for reporting ≥5, ≥10 and ≥15 symptoms respectively. This trend was generally strongest for panel beaters (ORs of 2.1, 3.3 and 8.2 for ≥5, ≥10 and ≥15 symptoms respectively). Associations with specific symptom domains showed increased risks for neurological (OR 4.2), psychosomatic (OR 3.2), mood (OR 2.1), memory (OR 2.9) and memory and concentration symptoms combined (OR 2.4; all p<0.05). Workers who had worked for 10-19 years or 20+ years in the collision repair industry reported consistently more symptoms than those who had only worked less than 10 years even after adjusting for age. However, those who worked more than 20 years generally reported fewer symptoms than those who worked 10-19 years, suggesting a possible healthy worker survivor bias. Despite low airborne solvent exposures, vehicle collision repair spray painters and panel beaters continue to be at risk of symptoms of neurotoxicity

Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure

Background: Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP. Methods: We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures. Results: The mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (−2.57 dB change in MD per every 3 mmHg increase in VIMmap; P \u3c 0.001) and diurnal MAP dips (changes in the MD ranged from −2.56 to −3.19 dB; P \u3c 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with −1.14 dB changes in MD [95% confidence interval (CI), −1.90 to −0.40] and 0.01 larger optic disc cupping (95% CI, 0.01–0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022). Conclusion: Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG)