Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress.

BACKGROUND: Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. RESULTS: Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. CONCLUSIONS: Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress

Anti-reflection coatings for submillimeter silicon lenses

Low-loss lenses are required for submillimeter astronomical applications, such as instrumentation for CCAT, a 25 m diameter telescope to be built at an elevation of 18,400 ft in Chile. Silicon is a leading candidate for dielectric lenses due to its low transmission loss and high index of refraction; however, the latter can lead to large reflection losses. Additionally, large diameter lenses (up to 40 cm), with substantial curvature present a challenge for fabrication of antireflection coatings. Three anti-reflection coatings are considered: a deposited dielectric coating of Parylene C, fine mesh structures cut with a dicing saw, and thin etched silicon layers (fabricated with deep reactive ion etching) for bonding to lenses. Modeling, laboratory measurements, and practicalities of fabrication for the three coatings are presented and compared. Measurements of the Parylene C anti-reflection coating were found to be consistent with previous studies and can be expected to result in a 6% transmission loss for each interface from 0.787 to 0.908 THz. The thin etched silicon layers and fine mesh structure anti-reflection coatings were designed and fabricated on test silicon wafers and found to have reflection losses less than 1% at each interface from 0.787 to 0.908 THz. The thin etched silicon layers are our preferred method because of high transmission efficiency while having an intrinsically faster fabrication time than fine structures cut with dicing saws, though much work remains to adapt the etched approach to curved surfaces and optics < 4" in diameter unlike the diced coatings

The Implementation of Whole-School Approaches to Transform Mental Health in UK Schools: A Realist Evaluation Protocol

Evidence suggests that mental health interventions are more effective when they consider the whole context of schools; addressing the needs of all students, their families, and staff; otherwise known as a whole-school approach (WSA). The UK Government is piloting WSAs to transform mental health and wellbeing by locating educational mental health practitioners in educational settings across England. This study aims to develop a ‘bottom-up’ understanding of the contextual factors and mechanisms that underlie WSAs in Trailblazer schools in the North East and North Cumbria, to gain insight into the facilitators and barriers of delivering a WSA, and optimal evaluation methods. To undertake a realist evaluation, we included the generation of initial programme theories from existing academic literature and policy documents; ‘theory gleaning’ interviews with NHS/local authority stakeholders, Trailblazer staff and school senior leaders; refining and development of theories; and individual interviews and focus groups with pupils, parent/carers and school staff. The findings will enable Trailblazer partners to better understand how their WSAs to mental health contain the essential components for transformation in schools in the region. This will contribute to the embedding of continuous evaluation into regional Trailblazers’ practice for participating schools, for subsequent annual waves and producing relevant findings for non-Trailblazer schools. Complementing the national evaluation of all 25 Wave 1 Trailblazer pilot sites, this study will generate an explanatory theoretical account of how to optimally design, implement and evaluate WSAs by exploring the contextual factors associated with implementation of WSAs

Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial

Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the PARP inhibitor olaparib significantly improves progression-free survival versus placebo. We assessed the effect of maintenance olaparib on overall survival in patients with platinum-sensitive recurrent serous ovarian cancer, including those with BRCA1 and BRCA2 mutations (BRCAm). / Methods: In this randomised, placebo-controlled, double-blind, phase 2 trial involving 82 sites across 16 countries, patients with platinum-sensitive recurrent serous ovarian cancer who had received two or more courses of platinum-based chemotherapy and had responded to their latest regimen were randomly assigned (1:1) using a computer-generated sequence to receive oral maintenance olaparib (as capsules; 400 mg twice a day) or a matching placebo by an interactive voice response system. Patients were stratified by ancestry, time to progression on penultimate platinum, and response to most recent platinum. Patients and investigators were masked to treatment assignment by the use of unique identifiers generated during randomisation. The primary endpoint of the trial was progression-free survival. In this updated analysis, we present data for overall survival, a secondary endpoint, from the third data analysis after more than 5 years’ follow-up (intention-to-treat population). We did the updated overall survival analysis, described in this Article at 77% data maturity, using a two-sided α of 0·95%. As the study was not powered to assess overall survival, this analysis should be regarded as descriptive and the p values are nominal. We analysed randomly assigned patients for overall survival and all patients who received at least one dose of treatment for safety. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT00753545. / Findings: Between Aug 28, 2008, and Feb 9, 2010, 265 patients were randomly assigned to olaparib (n=136) or placebo (n=129). 136 patients had deleterious BRCAm. The data cutoff for this analysis was Sept 30, 2015. An overall survival advantage was seen with maintenance olaparib versus placebo in all patients (hazard ratio [HR] 0·73 [95% CI 0·55–0·96]; nominal p=0·025, which did not meet the required threshold for statistical significance [p<0·0095]; median overall survival was 29·8 months [95% CI 26·9–35·7] for those treated with olaparib vs 27·8 months [24·9–33·7] for those treated with placebo), and in patients with BRCAm (HR 0·62 [95% CI 0·41–0·94] nominal p=0·025; 34·9 months [95% CI 29·2–54·6] vs 30·2 months [23·1–40·7]). The overall survival data in patients with BRCA wild-type were HR 0·83 (95% CI 0·55–1·24, nominal p=0·37; 24·5 months [19·8–35·0] for those treated with olaparib vs 26·6 months [23·1–32·5] for those treated with placebo). 11 (15%) of 74 patients with BRCAm received maintenance olaparib for 5 years or more. Overall, common grade 3 or worse adverse events in the olaparib and placebo groups were fatigue (11 [8%] of 136 patients vs four [3%] of 128) and anaemia (eight [6%] vs one [1%]). 30 (22%) of 136 patients in the olaparib group and 11 (9%) of 128 patients in the placebo group reported serious adverse events. In patients treated for 2 years or more, adverse events in the olaparib and placebo groups included low-grade nausea (24 [75%] of 32 patients vs two [40%] of five), fatigue (18 [56%] of 32 vs two [40%] of five), vomiting (12 [38%] of 32 vs zero), and anaemia (eight [25%] of 32 vs one [20%] of five); generally, events were initially reported during the first 2 years of treatment. / Interpretation: Despite not reaching statistical significance, patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy after platinum-based chemotherapy appeared to have longer overall survival, supporting the reported progression-free survival benefit. Clinically useful long-term exposure to olaparib was seen with no new safety signals. Taken together, these data support both the long-term clinical benefit and tolerability of maintenance olaparib in patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer. / Funding: AstraZeneca

Imaging X-Ray Polarimeter Explorer Systems Engineering Approach and Implementation

The Imaging X-ray Polarimetry Explorer (IXPE) is a NASA Small Explorer x-ray astrophysics mission being implemented by a geographically dispersed team. Each IXPE partner provides unique capabilities and experience which are utilized to design, build and launch the IXPE observator. A rigorous and iterative systems engineering approach is essential to ensuring the successful realization of reliable and cost effective IXPE mission system. The IXPE collaboration and observatory complexity provide both unique challenges and advantages for project systems engineering. The project uses established and tailored systems engineering (SE) methods and teaming approaches to achieve the IXPE mission goals. The IXPE systems engineering team spans all partner organizations. Currently, the project is in system integration and test working through structural environmental testing–vibration testing is just starting. Systems work is now focused on requirements management and maturity assessments, requirements verification and validation via sell-off packages (SOP) and interface control document (ICD) verification while supporting environmental test planning and execution. IXPE verification, validation and characterization (V&V) starts at the component/unit level and rolls up to appropriate higher levels where V&V compliance is assured by collaborative development by the cross-organizational V&V Team. This paper provides a technical summary of the IXPE concept of operations and mission-system (payload, spacecraft, observatory, ground system, launch vehicle), overviews the IXPE systems engineering approach (communications, project reviews, requirements analysis and management, baseline design and design trade studies, interfaces definition and documentation, resource management), describes the verification, validation and characterization activities (requirements validation, models and simulations validation, systems integration and test (I&T), system validation), discusses risk and opportunities philosophy and implementation, outlines COVID 19 accommodations, itemizes some key challenges and lessons-learned followed by the path to launch and conclusions

Political Contest and Oppositional Voices in Postconflict Democracy:The Impact of Institutional Design on Government–Media Relations

The media are considered to play a crucial democratic role in the public sphere through representing political issues to the public (Gelders et al. 2007); facilitating deliberation, public opinion formation and political participation (Habermas 1989); acting as the 'watchdog' of powerful societal institutions (Norris 2000); and in assisting in the development of civil society in politically fragile and divided contexts (Taylor 2000). Journalists are expected to perform their news reporting within the framework of public interest values, such as objectivity, impartiality, public service, autonomy, and a critical questioning of power (Street 2001). Yet, it is acknowledged that political, cultural, organisational, economic, and relational factors affect this journalistic ideal (Davis 2010). In deeply divided, post-conflict societies, ethno-political antagonisms are fundamental to almost all aspects of civic life, yet there is limited research into how government-media relations operate in such contexts. Most media-politics studies focus on Western majoritarian parliamentary or presidential systems - that is, any system that has clear ‘winners’ and ‘losers’ after elections - and where institutional factors are considered, the focus is largely on how party systems impact on journalism (e.g. Çarkoğlu et al. 2014; Hallin and Mancini 2004; Sheafer and Wolfsfeld 2009). This focus however, neglects important institutional variables, such as mandatory coalition, proportionality and special cross-community voting arrangements, which pertain in more constitutionally complex democracies and which may have a significant impact on media-politics relations

Primary care medication safety surveillance with integrated primary and secondary care electronic health records: a cross-sectional study

Introduction: The extent of preventable medication-related hospital admissions and medication-related issues in primary care is significant enough to justify developing decision support systems for medication safety surveillance. The prerequisite for such systems is defining a relevant set of medication safety-related indicators and understanding the influence of both patient and general practice characteristics on medication prescribing and monitoring. Objective: The aim of the study was to investigate the feasibility of linked primary and secondary care electronic health record data for surveillance of medication safety, examining not only prescribing but also monitoring, and associations with patient- and general practice-level characteristics. Methods: A cross-sectional study was conducted using linked records of patients served by one hospital and over 50 general practices in Salford, UK. Statistical analysis consisted of mixed-effects logistic models, relating prescribing safety indicators to potential determinants. Results: The overall prevalence (proportion of patients with at least one medication safety hazard) was 5.45 % for prescribing indicators and 7.65 % for monitoring indicators. Older patients and those on multiple medications were at higher risk of prescribing hazards, but at lower risk of missed monitoring. The odds of missed monitoring among all patients were 25 % less for males, 50 % less for patients in practices that provide general practitioner training, and threefold higher in practices serving the most deprived compared with the least deprived areas. Practices with more prescribing hazards did not tend to show more monitoring issues. Conclusions:Systematic collection, collation, and analysis of linked primary and secondary care records produce plausible and useful information about medication safety for a health system. Medication safety surveillance systems should pay close attention to patient age and polypharmacy with respect to both prescribing and monitoring failures; treat prescribing and monitoring as different statistical processes, rather than a combined measure of prescribing safety; and audit the socio-economic equity of missed monitoring