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Introduction: Observational studies are increasingly being used to provide evidence on the real-world effectiveness of medications for preventing vascular diseases, such as stroke. We investigated whether the real-world effectiveness of treatment with lipid-lowering medications after ischemic stroke is affected by prevalent-user bias. Methods: An observational cohort study of 90-day survivors of ischemic stroke using person-level data from the Australian Stroke Clinical Registry (2012–2016; 45 hospitals) linked to administrative (pharmaceutical, hospital, death) records. The use of, and adherence to (proportion of days covered Results: Of 11,217 eligible patients (median age 72 years, 42% female), 9,294 (83%) used lipid-lowering medications within 90 days post-discharge, including 5,479 new users. In both prevalent-user and new-user designs, nonusers (vs. users) had significantly greater rates of mortality (hazard ratio [HR] 2.35, 95% CI: 1.89–2.92) or all-cause readmissions (HR 1.22, 95% CI: 1.05–1.40) but not cardiovascular disease readmission. In contrast, associations between having poor (vs. good) adherence on outcomes were stronger among new users than all users. Among new users, having poor adherence was associated with greater rates of mortality (HR 1.48, 95% CI: 1.12–1.96), all-cause readmission (HR 1.14, 95% CI: 1.02–1.27), and cardiovascular disease readmission (HR 1.20, 95% CI: 1.01–1.42). Conclusions: The real-world effectiveness of treatment with lipid-lowering medications after stroke is attenuated when evaluated based on prevalent-user rather than new-user design. These findings may have implications for designing studies on the real-world effectiveness of secondary prevention medications.

Plant RNA viruses are used as delivery vectors for their high level of accumulation and efficient spread during virus multiplication and movement. Utilizing this concept, several viral-based guide RNA delivery platforms for CRISPR-Cas9 genome editing have been developed. The CRISPR-Cas9 system has also been adapted for epigenome editing. While systems have been developed for CRISPR-Cas9 based gene activation or site-specific DNA demethylation, viral delivery of guide RNAs remains to be developed for these purposes. To address this gap we have developed a tobacco rattle virus (TRV)-based single guide RNA delivery system for epigenome editing in Arabidopsis thaliana. Because tRNA-like sequences have been shown to facilitate the cell-to-cell movement of RNAs in plants, we used the tRNA-guide RNA expression system to express guide RNAs from the viral genome to promote heritable epigenome editing. We demonstrate that the tRNA-gRNA system with TRV can be used for both transcriptional activation and targeted DNA demethylation in Arabidopsis. We achieved up to ~8% heritability of the induced demethylation phenotype in the progeny of virus inoculated plants. We did not detect the virus in the next generation, indicating effective clearance of the virus from plant tissues. Thus, TRV delivery, combined with a specific tRNA-gRNA architecture, provides for fast and effective epigenome editing.Author summaryThe discovery of CRISPR-CAS9 and its non-catalytic variants have provided enormous capacity for crop improvement and basic research by modifying the genome and the epigenome. The standard methods for delivering genome and epigenome editing reagents to plants consist of generating stable transgenic lines through tissue culture processes, which have several drawbacks including the need for plant regeneration and crossing. To overcome some of these challenges, plant virus-based platforms are being developed for genome editing. Although viruses have a limited cargo capacity, limiting the use of viruses to encode entire editing systems, guide RNAs have been successfully delivered to transgenic CAS9 expressing plants for genome editing. However, the use of viruses for CRISPR-based epigenome editing and transcriptional activation have not yet been explored. In this study we show that viral delivery of guide RNAs using a modified tobacco rattle virus can be used for transcriptional activation and heritable epigenome editing. This study advances the use of plant RNA viruses as delivery agents for epigenome editing.

Distance education has historically had lower completion rates. Several models of persistence, for on-campus students, indicate that students’ financial status affects their decision to per...

INTRODUCTION: The question of whether the practice of professional supervision is effective, and how its effectiveness can be measured, has been debated by both social work and other professions. This study explored how practitioners, supervisors and managers in Aotearoa New Zealand currently evaluate the supervision they receive, provide and/or resource. The study was interprofessional involving counsellors, mental health nurses, psychologists and social workers. This article focuses on the findings from the social work cohort.METHODS: Through an on-line Qualtrics survey participants were asked: 1) how they currently evaluated professional/clinical supervision; and 2) how they thought professional/clinical supervision could be evaluated. Data were extracted through the Qualtrics reporting functions and thematic analysis was used to identify themes. A total of 329 participants completed the survey of which 145 (44%) were social workers. FINDINGS: A majority of the social work participants reported that they evaluated supervision in some form. No culture or policy emerged regarding supervision evaluation, but social workers expressed interest in training and resources to assist evaluation and some saw a supportive and endorsement role for the professional or regulatory bodies. An unexpected finding was reports of unsatisfactory and harmful supervision.CONCLUSION: Evaluation of supervision is an activity with which social workers engage, but further research is needed to explore how evaluation can be embedded in supervision practice. More critically, a broader audit is required to reconsider the definition and model of social work supervision in Aotearoa New Zealand and the environments within which supervision occurs.

Plant RNA viruses are used as delivery vectors for their high level of accumulation and efficient spread during virus multiplication and movement. Utilizing this concept, several viral-based guide RNA delivery platforms for CRISPR-Cas9 genome editing have been developed. The CRISPR-Cas9 system has also been adapted for epigenome editing. While systems have been developed for CRISPR-Cas9 based gene activation or site-specific DNA demethylation, viral delivery of guide RNAs remains to be developed for these purposes. To address this gap we have developed a tobacco rattle virus (TRV)-based single guide RNA delivery system for epigenome editing in Arabidopsis thaliana. Because tRNA-like sequences have been shown to facilitate the cell-to-cell movement of RNAs in plants, we used the tRNA-guide RNA expression system to express guide RNAs from the viral genome to promote heritable epigenome editing. We demonstrate that the tRNA-gRNA system with TRV can be used for both transcriptional activation and targeted DNA demethylation of the FLOWERING WAGENINGEN gene in Arabidopsis. We achieved up to ~8% heritability of the induced demethylation phenotype in the progeny of virus inoculated plants. We did not detect the virus in the next generation, indicating effective clearance of the virus from plant tissues. Thus, TRV delivery, combined with a specific tRNA-gRNA architecture, provides for fast and effective epigenome editing., Author summary The discovery of CRISPR-CAS9 and its non-catalytic variants have provided enormous capacity for crop improvement and basic research by modifying the genome and the epigenome. The standard methods for delivering genome and epigenome editing reagents to plants consist of generating stable transgenic lines through tissue culture processes, which have several drawbacks including the need for plant regeneration and crossing. To overcome some of these challenges, plant virus-based platforms are being developed for genome editing. Although viruses have a limited cargo capacity, limiting the use of viruses to encode entire editing systems, guide RNAs have been successfully delivered to transgenic CAS9 expressing plants for genome editing. However, the use of viruses for CRISPR-based epigenome editing and transcriptional activation have not yet been explored. In this study we show that viral delivery of guide RNAs using a modified tobacco rattle virus can be used for transcriptional activation and heritable epigenome editing. This study advances the use of plant RNA viruses as delivery agents for epigenome editing.

The Gonzaga of Mantua, in common with other ruling houses, were accustomed to utilising the occasions of religious feasts to promote social cohesion, civic pride and dynastic loyalty. This paper examines three such festive celebrations, to show how the Marquis of Mantua, Francesco II, and his court advisers could turn them to Gonzaga advantage. Each year on the Feast of the Ascension, the population of Mantua was swollen with pilgrims drawn to the city to venerate the relic of the Most Precious Blood of Christ held in the church of Sant’ Andrea. The processional route passed by the house of a Jew, lying somewhat apart from the city’s Jewish ghetto. With permission, the Jew had removed from its exterior a fresco of the Virgin, Christ Child and saints. During the vigil of Ascension Day 1495, stirred by anti-Jewish sentiment, the processing crowd erupted into a riot in which the Jew’s house was vandalised. To compensate for the removal of the holy image, despite his having secured prior consent, the unfortunate Jew was made to pay the expenses of having a new painting made, the Madonna della Vittoria by Andrea Mantegna, today displayed in the Louvre. The painting was a votive altarpiece, to give thanks to the Virgin for having saved the marquis in battle and his victory at Fornovo on 6 July 1495. On the twelve-month anniversary of the battle, a lavish commemoration was organised, whereby the finished canvas was solemnly processed through the streets of Mantua from Mantegna’s house to Santa Maria della Vittoria, a little church hurriedly erected to receive the painting on the site of the expunged fresco. A sermon was preached in front of the altarpiece on the street outside, the portrait of Francesco allegedly moving everyone to tears. The following year, in 1497, Francesco brought forward by four days the commemoration of his victory to coincide with the Feast of the Visitation, thus grafting his temporal triumph onto an assured, sacred ritual, to be annually inscribed in the city’s fabric.

The evaluation of professional supervision has been a focus for discussion in the supervision literature over past decades. A review of the literature in this area, however, suggests that evaluation has been differently defined, variously addressed, and a range of outcomes reported. The present study reports the findings of the first stage of a three-stage study of evaluation in professional supervision in Aotearoa/New Zealand. Experienced practitioners from the four professions of counselling, mental health nursing, psychology, and social work were interviewed to explore how evaluation in professional supervision is understood and actioned in practice. Twenty four semistructured interviews were conducted with supervisees, supervisors, and managers from each of the identified professions. The findings from these interviews indicate that a majority of participants applied some form of evaluation to their supervision arrangement. These evaluations, however, did not reflect an overarching organizational or professional culture of formal evaluation, but rather, an individualized ad-hoc process initiated by one or both of the participants (supervisor and supervisee). These evaluations focussed predominantly on the process, rather than the outcomes, of supervision. While many respondents expressed interest in a formal process for evaluating supervision, a number of concerns were also raised. These concerns included a lack of evaluation skills and resource, the potential for formal evaluation to have a negative impact on the supervision relationship, the importance of maintaining the boundaries of confidentiality, and a wariness regarding the possible use of any information gathered.

A three-component intervention was implemented with 47 youth with autism spectrum disorders (ASD) as they transitioned from high school to adult life. The youth, ages 16 to 19 years, were randomly assigned to a Year 1 group or a Year 2 group. Participants in the Year 1 group received a transition planning intervention consisting of (a) group training sessions for families in the transition process, (b) person-centered planning meetings facilitated by project staff, and (c) follow-up assistance with career exploration and plan implementation. Data were collected pre- and post implementation to measure student and family expectations, self-determination, and career decision-making ability. The Year 2 group began receiving services following the second data collection point. Participants in the Year 1 group reported statistically significant increases in all four measured variables, whereas the Year 2 group showed no significant changes. Implications for redesigning transition services for this population are discussed.

Trauma is a devastating consequence that affects the human identity resulting in the shattering of basic trust in oneself, others, and God. Often people suffering the effects of trauma turn to the Christian community for answers and assistance. Through understanding how trauma affects a person the Christian community is better equipped to walk along side those who are in the recovery process. Compassion creates a safe place for an individual to reveal the depths of emotional pain. The attribute of resilience enables the traumatized individual to continue moving through the recovery process. Six narratives were examined using constructive narrative theology as the methodology. From weaving these narratives together it became apparent that the Christian community can best aid a traumatized person by listening to their story, entering into their lament, drawing out their metaphorical and symbolic language, lifting them up in prayer, and leaving them in God's hands. Thesis Master of Arts (MA)

This article describes the design and development of a professional development program based upon research on the competencies necessary for online teaching success [1] conducted at Penn State University in 2009-2010. The article highlights how the results of this research are being aligned with various professional development courses comprising the certificate program for online faculty at Penn State’s World Campus. This article describes the process of research design and implementation to the direct application for professional development.

This exploratory study examined teaching behaviors, attitudes, and beliefs (referred to as tasks) that reflect potential competencies for online teaching success. In this study, teaching tasks are those tasks performed during course delivery. Based on faculty interviews and a review of relevant research, 64 teaching tasks were identified and included in 7-point Likert scale survey instrument. It was distributed to experienced online faculty and staff asking them to rate the level of importance of a list of teaching tasks and resulted in a sample of 197 responses. Of interest was the fact that over half of the teaching tasks had a rating of 6.0 on the 7-point scale and more than half of the tasks that were rated 6.0 or higher did not load into categories using factor analysis. Further examination of the results is required to determine why highly rated teaching tasks did not fall (load onto) into any factor. Results of the importance of the tasks will form the basis of faculty development efforts aimed at providing faculty with professional development in critical competencies to ensure online teaching success.

This study investigated what occurs in an individual's life when their culture is changed or irretrievably lost; and it investigated how an individual then regains personal meaning during a time of cultural loss and change. Peter Marris' innovative Theory of Loss and Change was used as the theoretical basis for the study. This theory states that a grief-like reformulation process occurs for individuals who experience any irretrievable loss of culture. The Native Indian cultures of British Columbia were used as the cultural foundation. Three Native Indian elders were interviewed and their life histories recorded (Bertaux, 1981). The data collected was then used as multiple case studies and analyzed according to Yin (1984) and Stake (1980). Cross-matching of patterns of loss and change, and patterns of recovery of personal meaning revealed six primary forms of loss and change in the elder's lives, and five primary characteristics of recovery of personal meaning. Secondary forms and characteristics in each area were identified as well. Marris' Theory of Loss and Change was supported. It was also expanded to include the Native Indian cultures of British Columbia. In addition, the emotional elements of the reformulation process were specified. The outcome of the study was a cognitive framework useful in understanding the Native Indian cultures in British Columbia and the personal conflicts of Native Indian individuals.

The perception of the voiced and voiceless velar and pharyngeal fricatives/v, x, ʕ, ħ/ and of /s, s/ in Colloquial Egyptian Arabic was examined to determine if the presence of the first two or three formants in /v, x, ʕ, ħ/ results in continuous perception, in contrast to an expected categorical perception of /s, s/ which lack these formants. Three 12‐step continua containing /ə/‐c‐/ə/ nonsense words were synthesized. For the/s‐s/ continuum, the center of a high‐frequency resonance was varied in equal steps. For the /x‐ħ/ and /v‐ʕ/ continua F1 was varied. Eight native speakers were asked to identify 16 tokens of each stimulus and discriminate each two‐step stimulus pair 24 times in a 41AX discrimination task. While /v‐ʕ/ showed continuous or less categorical perception than /s‐s/, /x‐ħ/ was perceived somewhat categorically. This may be explained by the fact that since /x/ and /ħ/are voiceless, they may contain less information about the lower formants than do their voiced counterparts /v/ and /ʕ/. [T...

Synthesizing speech by concatenating allophones is a new application of linear predictive coding (LPC) that provides an unlimited vocabulary. Since the stored units are individual speech sounds, any English word can be synthesized by concatenating the appropriate sounds. Our inventory contains 59 speech sounds and five pauses. Each allophone was created by extracting it from the digital waveform of a word, and then synthesizing it. The sounds are called allophones because some phonemes have two or three versions for different environments. For example, /k/ and /g/ each have three allophones: one to be used before front vowels, one before back vowels, and one in final position. In contrast, research revealed that the same /p/ can be used in all environments. Isolating final /r/ from preceding vowels was impossible because of important transitional information. Therefore there are five phonemically unique V + /r/ combinations. Due to the omission of many transitions, allophone synthesis suffers from reduced...

The acoustic cue separating /s/ and /s/ was studied, using synthetic speech stimuli, in the context of two different following [ae]'s: one appropriate for a large vocal tract and one for a small vocal tract. For each vocal tract size, the center frequency of the frictional portion of the stimuli was varied in ten steps from 2974 to 4455 Hz. In preliminary experiments, it was found that listeners have a reasonably consistent boundary along this scale at which they stop hearing /s/ and start hearing /s/. It was hypothesized that a listener's boundary would be higher for the small‐vocal‐tract stimuli than for the large‐vocal‐tract stimuli. Nineteen subjects who were asked to identify 40 tokens of each stimulus showed an upward boundary shift of varying magnitude for the small‐vocal‐tract stimuli as compared with the large‐vocal‐tract stimuli. This result suggests the /s/‐/s/ cue is dependent on vocal tract size.