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Purpose: To collect data on efficacy and safety of brolucizumab 6 mg drug product intended for commercialization in patients with neovascular age-related macular degeneration to support comparability to brolucizumab product used in the Phase III HAWK and HARRIER studies. Methods: The HAWK extension study was a 24-week, double-masked, multicenter study of patients with neovascular age-related macular degeneration who completed the 96-week HAWK core study. All patients were planned to receive three intravitreal injections of either brolucizumab 6 mg or aflibercept 2 mg. Key endpoint measures included change in best-corrected visual acuity and central subfield thickness from baseline, and incidence and characteristics of treatment emergent adverse events. Results: Best-corrected visual acuity gain and central subfield thickness reduction observed at the end of the core study were maintained to Week 24 of the extension study. There was no indication of difference in the safety profile of the brolucizumab 6 mg drug product intended for commercialization and the brolucizumab 3 mg or 6 mg drug product used in the Phase III clinical trials. Conclusions: Efficacy and safety with the intended commercial formulation of brolucizumab 6 mg in neovascular age-related macular degeneration patients was consistent with that observed in the Phase III studies. [ABSTRACT FROM AUTHOR]

St. George Jackson Mivart is mostly remembered as a cautionary tale. If Mivart is mentioned at all in modern debates, it is to offer an example of how not to do biology and theology. However, in this paper I argue that, ongoing developments in evolutionary biology have produced genuine alternatives to strict neo-Darwinism that not only seek to downplay the role of natural selection, but do so in ways that are strikingly reminiscent of Mivart's unpopular theory. Similarly, modern Thomists are also taking an approach to science and religion that mirrors Mivarts own approach. [ABSTRACT FROM AUTHOR]

As the counseling profession has increased focus on spiritual integration into counseling sessions, such integration brings necessary attention to professional ethics. While ethical guidelines mandate that counselors not impose values on clients, this has oftentimes been confused with the false idea that counselors who are Christian may not or cannot practice ethically due to potential conflicts between ethical practice and religious beliefs. This study helps explore professional counselors' understanding of the integration of Christianity into professional counseling. Such an understanding may help correct biases regarding ethical use of Christianity in professional mental health counseling. [ABSTRACT FROM AUTHOR]

In this paper we use a case study, the co-production of a prostate cancer app with, and for, Black British African-Caribbean communities, to discuss benefits and tensions of inclusive practice and allyship. We view our collaborators as joint partners, and joint allies, for the Black British African-Caribbean community. Here, we document the research process and highlight successful aspects of our collaboration such as mentoring, recruitment, ideas on the format and presentation of the app, supportive data collection practices, useful community feedback and promotion of the app. We also highlight points in the research process that in hindsight needed more discussion and careful negotiation. We end with some recommendations based on our experience. [ABSTRACT FROM AUTHOR]

This paper provides a critical analysis of the Chartered Institute for Management of Sport and Physical Activity's (CIMSPA) transformative aspirations for UK Higher Education (HE) based Sport and Physical Activity Vocational Education and Training (SPAVET) provision. In doing so, we apply selected elements of Giddens' Structuration theory to offer an analysis of CIMSPA's structural properties (as rules and resources) and dimensions (signification, domination and legitimation). Illustration of CIMSPA's structural properties and dimensions was developed through adopting an institutional analysis strategy alongside a document analysis method. Publicly available strategic documents and web-based resources (N = 18) were selected and analysed using open-coding techniques. Our analysis shows how continued state-sanctioned decentralisation of the UK HE sector has led to CIMSPA becoming an increasingly influential transformative structure; attempting to use its structural dimensions and resources as a medium to gain and exercise power, to promote (signification) – market-orientated discourses, practices and pedagogies in HEI provision, (domination) – in an attempt to significantly influence regulatory control over UK SPAVET provision and (Legitimation) – create partnerships which normalise its position and message within selected UK HEIs. We conclude that whilst the transformative aspirations of CIMSPA offer a number of possibilities for the HE SPAVET sector, they also raise critical questions. The central issue requiring debate is how these aspirations shift dialectical control towards vocationally focused, market-orientated principles and away from the liberal educational, research-led principles of some current UK HE SPAVET provision. [ABSTRACT FROM AUTHOR]

Factors influencing cyanobacterial blooms in Lake Horowhenua, Aotearoa/New Zealand, have been deduced from over 40 yrs routine monitoring data, detailed studies and high frequency (15-min interval) data from an in-lake monitoring buoy. Lake Horowhenua is currently hypertrophic but flips between a winter clear-water, macrophyte dominated phase (Potamogeton crispus), and a turbid phytoplankton dominated phase with substantial cyanobacterial (Microcystis sp.) blooms from mid-summer to autumn. Nitrogen for growth comes from agriculture and horticulture via groundwater and spring-fed streams. Phosphorus is released from the sediment when the weed beds die back. These nutrients stimulate the growth of Microcystis sp., until the water temperature falls below 15°C. Microcystis sp can raise the pH to over 10, which releases P from the sediment, sustaining its growth. High pH transforms non-toxic ammonium-N released from the sediment to toxic unionised NH3, which may contribute to fish kills in summer/autumn. Management strategies cannot use P-inactivation agents for cultural reasons and eradicating the macrophyte beds by spraying would cause the lake to permanently flip to a turbid state. Management of the macrophyte beds with a weed harvester is being trialled to allow a gradual replacement of P. crispus with indigenous species from the seed bank in the sediment. [ABSTRACT FROM AUTHOR]

In 2014, the Association of American Medical Colleges (AAMC) published 13 Core Entrustable Professional Activities (EPAs) that graduating students should be able to perform with indirect supervision when entering residency. A ten-school multi-year pilot was commissioned to test feasibility of implementing training and assessment of the AAMC's 13 Core EPAs. In 2020-21, a case study was employed to describe pilot schools' implementation experiences. Teams from nine of ten schools were interviewed to identify means and contexts of implementing EPAs and lessons learned. Audiotapes were transcribed then coded by investigators using conventional content analysis and a constant comparative method. Coded passages were organized in a database and analyzed for themes. Consensus among school teams regarding facilitators of EPA implementation included team commitment to piloting EPAs; agreement that: proximal EPA adoption with curriculum reform facilitates EPA implementation; EPAs 'naturally fit' in clerkships and provided opportunity for schools to reflect on and adjust curricula and assessments; and inter-school collaboration bolstered individual school progress. Schools did not make high-stakes decisions about student progress (e.g., promotion, graduation), yet EPA assessment results complemented other forms of assessment in providing students with robust formative feedback about their progress. Teams had varied perceptions of school capability to implement an EPA framework, influenced by various levels of dean involvement, willingness, and capability of schools to invest in data systems and provide other resources, strategic deployment of EPAs and assessments, and faculty buy-in. These factors affected varied pace of implementation. Teams agreed on the worthiness of piloting the Core EPAs, but substantial work is still needed to fully employ an EPA framework at the scale of entire classes of students with enough assessments per EPA and with required data validity/reliability. Recommendations stemming from findings may help inform further implementation efforts across other schools adopting or considering an EPA framework. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective study is to evaluate the association of total therapy time during inpatient rehabilitation and gain in functional independence for patients admitted to an inpatient rehabilitation facility (IRF). The study utilized a retrospective design that included all IRF patients from three IRFs in California from January 1, 2012 to December 31, 2013. Patient data collected as part of usual, routine medical, and rehabilitation care were used and includes demographics, medical variables, and functional outcomes data. There were 3212 patients discharged from the three IRFs, with 2,777 patients having received speech language pathology (SLP) therapy along with occupational therapy and physical therapy. Speech language pathology services were not provided for 435 patients in the database. Our results support that among all types of patients, increased therapy hours were associated with increased functional gains. For total functional independence measure (FIM) gain, an additional hour of PT therapy per day was associated with an increase of 7.55 FIM gain points (p < 0.001) and an additional hour of OT therapy per day was associated with an increase of 1.16 FIM gain points (p = 0.045), when adjusted for other variables in the model. SLP hours per day did not remain in the FIM gain model. The findings of this study add to the understanding of therapy time and functional gain in an inpatient rehabilitation program. There is a positive relationship between total therapy time and functional gain. In the future determining the intensity and the related therapy activities provided will be needed to impact functional change. This has implications for shaping rehabilitation practice in the future. Increased number of therapy hours were associated with functional gains in an inpatient rehabilitation program for all types of patients. An additional hour of physical therapy per day was associated with an increase of 7.55 functional independence measure (FIM) point gain. An additional hour of occupational therapy per day was associated with an increase of 1.16 FIM point gain. Determining the intensity and related activities are needed to impact functional change which has implications for shaping rehabilitation practice. [ABSTRACT FROM AUTHOR]

The Scottish verdict of not proven represents a second acquittal verdict which is not legally defined. Existing research into the influence of the not proven verdict on jury decision making is modest. The main aim of the current study was therefore to investigate the influence of verdict systems (two vs three) on juror decision making. The effect of pre-trial bias and evidence anchors on juror judgements were also examined. One-hundred and twenty-eight mock jurors listened to two homicide vignettes and were asked to rate their belief of guilt of the accused and to give a verdict in both trials. The results suggest that pre-trial bias was a significant predictor of both verdict choice and belief of guilt, whereas evidence anchors were not a significant predictor of either. Finally, both guilty and not guilty verdicts were given with increased frequency in the two-verdict system when compared to the three-verdict system. [ABSTRACT FROM AUTHOR]

Hazard studies for nanomaterials (NMs) commonly assess whether they activate an inflammatory response. Such assessments often rely on rodents, but alternative models are needed to support the implementation of the 3Rs principles. Zebrafish (Danio rerio) offer a viable alternative for screening NM toxicity by investigating inflammatory responses. Here, we used non-protected life stages of transgenic zebrafish (Tg(mpx:GFP)i114) with fluorescently-labeled neutrophils to assess inflammatory responses to silver (Ag) and zinc oxide (ZnO) NMs using two approaches. Zebrafish were exposed to NMs via water following a tail fin injury, or NMs were microinjected into the otic vesicle. Zebrafish were exposed to NMs at 3 days post-fertilization (dpf) and neutrophil accumulation at the injury or injection site was quantified at 0, 4, 6, 8, 24, and 48 h postexposure. Zebrafish larvae were also exposed to fMLF, LTB4, CXCL-8, C5a, and LPS to identify a suitable positive control for inflammation induction. Aqueous exposure to Ag and ZnO NMs stimulated an enhanced and sustained neutrophilic inflammatory response in injured zebrafish larvae, with a greater response observed for Ag NMs. Following microinjection, Ag NMs stimulated a time-dependent neutrophil accumulation in the otic vesicle which peaked at 48 h. LTB4 was identified as a positive control for studies investigating inflammatory responses in injured zebrafish following aqueous exposure, and CXCL-8 for microinjection studies that assess responses in the otic vesicle. Our findings support the use of transgenic zebrafish to rapidly screen the pro-inflammatory effects of NMs, with potential for wider application in assessing chemical safety (e.g. pharmaceuticals). [ABSTRACT FROM AUTHOR]

In 2014, a fire at an open cut coal mine in South-eastern Australia burned for about 6 weeks. Residents of the adjacent town were exposed to high levels of fine particulate matter (PM2.5) during this period. Three and a half years after the event, this study aimed to investigate potential long-term impacts of short-term exposure to coal mine fire smoke on asthma. A cross-sectional analysis was undertaken in a group of exposed participants with asthma from Morwell (n = 165) and a group of unexposed participants with asthma from the control town of Sale (n = 64). Exposure was determined by modeled PM2.5 data for the mine fire period. Respiratory symptoms were assessed with a validated respiratory health questionnaire and symptom severity score. Asthma control was assessed with a validated questionnaire. Lung function testing included spirometry, bronchodilator response, and fraction of exhaled nitric oxide. There was no evidence that exposed participants had more severe asthma symptoms, worse lung function, or more eosinophilic airway inflammation than unexposed participants. However, there was some evidence that Morwell participants had more uncontrolled than well-controlled asthma, compared to the participants from Sale (adjusted relative risk ratio 2.71 95% CI: 1.02, 7.21, p =.046). Three and a half years after exposure, coal mine fire smoke did not appear to be associated with more severe asthma symptoms or worse lung function but might be associated with poorer asthma control. [ABSTRACT FROM AUTHOR]

In the U.S., black men are at highest risk for requiring kidney transplants but are among those least likely to register for organ donation. Prior outreach used videos culturally targeted for Black communities, yet registration rates remain insufficient to meet demand. Therefore, we assessed whether generic versus videos culturally targeted or personally tailored based on prior organ donation beliefs differentially increase organ donor registration. In a randomized controlled trial, 1,353 participants in Black-owned barbershops viewed generic, targeted, or tailored videos about organ donation. Logistic regression models assessed the relative impact of videos on: 1) immediate organ donor registration, 2) taking brochures, and 3) change in organ donation willingness stage of change from baseline. Randomization yielded approximately equal groups related to demographics and baseline willingness and beliefs. Neither targeted nor tailored videos differentially affected registration compared with the generic video, but participants in targeted and tailored groups were more likely to take brochures. Targeted (OR = 1.74) and tailored (OR = 1.57) videos were associated with incremental increases in organ donation willingness stage of change compared to the generic video. Distributing culturally targeted and individually tailored videos increased organ donor willingness stage of change among Black men in Black-owned barbershops but was insufficient for encouraging registration. Abbreviations: CI – confidence interval; DMV – Department of Motor Vehicles; BOBs – Black-owned barbershops; ODBI – organ donation belief index; ODWS – organ donation willingness stage of change; OR – odds ratio [ABSTRACT FROM AUTHOR]

With ever-increasing production and use of nanoparticles (NPs), there is a necessity to evaluate the probability of consequential adverse effects in individuals exposed to these particles. It is now understood that a proportion of NPs can translocate from primary sites of exposure to a range of secondary organs, with the liver, kidneys and spleen being some of the most important. In this study, we carried out a comprehensive toxicological profiling (inflammation, changes in serum biochemistry, oxidative stress, acute phase response and histopathology) of Ag NP induced adverse effects in the three organs of interest following acute exposure of the materials at identical doses via intravenous (IV), intratracheal (IT) instillation and oral administration. The data clearly demonstrated that bioaccumulation and toxicity of the particles were most significant following the IV route of exposure, followed by IT. However, oral exposure to the NPs did not result in any changes that could be interpreted as toxicity in any of the organs of interest within the confines of this investigation. The finding of this study clearly indicates the importance of the route of exposure in secondary organ hazard assessment for NPs. Finally, we identify Connexin 32 (Cx32) as a novel biomarker of NP-mediated hepatic damage which is quantifiable both (in vitro) and in vivo following exposure of physiologically relevant doses. [ABSTRACT FROM AUTHOR]