Search

Introduction: The importance of including people affected by research (e.g., community members, citizens or patient partners) is increasingly recognized across the breadth of institutions involved in connecting research with action. Yet, the increasing rhetoric of inclusion remains situated in research systems that tend to reward traditional dissemination and uphold power dynamics in ways that centre particular (privileged) voices over others. In research explicitly interested in doing research with those most affected by the issue or outcomes, research teams need to know how to advance meaningful inclusion. This study focused on listening to voices often excluded from research processes to understand what meaningful inclusion looks and feels like, and asked what contributes to being or feeling tokenized., Methods: In this deliberative dialogue study, 16 participants with experience of navigating social exclusions and contributing to research activities reflected on what makes for meaningful experiences of inclusion. Using a co-production approach, with a diversely representative research team of 15 that included patient and community partners, we used critically reflective dialogue to guide an inclusive process to study design and implementation, from conceptualization of research questions through to writing., Results: We heard that: research practices, partnerships and systems all contribute to experiences of inclusion or exclusion; the insufficiency or absence of standards for accountability amplifies the experience of exclusion; and inclusive practices require intention, planning, reflection and resources., Conclusions: We offer evidence-informed recommendations for the deeply relational work and practices for inclusivity, focused on promising practices for cultivating welcoming systems, spaces and relationships., Patient or Public Contribution: This work reflects a co-production approach, where people who use and are affected by research results actively partnered in the research process, including study design, data-generating activities, analysis and interpretation, and writing. Several of these partners are authors of this manuscript., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Inclusiveness, Support, Mutual Respect and Co-Build are the four pillars of patient engagement according to the Strategy for Patient-Oriented Research (SPOR). The aim of this manuscript is to describe the operationalization of these principles through the creation of a Patient Advisory Council (PAC) for the research study titled 'Re-Purposing the Ordering of Routine laboratory Tests (RePORT)'., Methods: Researchers collaborated with the Alberta SPOR SUPPORT Unit (AbSPORU) Patient Engagement Team to create a diverse PAC. Recruitment was intentional and included multiple perspectives and experiences. PAC meetings were held monthly, and patient research partners received support to function as co-chairs of the PAC. Patient research partners were offered training, support and tailored modalities of compensation to actively engage with the PAC. Regular member check-ins occurred through reflexivity and a formal evaluation of PAC member engagement., Results: The PAC included between 9 and 11 patient research partners, principal investigator, research study coordinator, improvement scientist, resident physician and support members from the AbSPORU team. Twelve monthly PAC meetings were held during the first phase of the project. The PAC made course-changing contributions to study design including study objectives, recruitment poster, interview guide and development of codes for thematic analysis. Patient research partners largely felt that their opinions were valued. Diversity in the PAC membership enhanced access to diverse patient participants. Furthermore, support for co-chairs and patient research partner members enabled active engagement in research. In addition, a culture of mutual respect facilitated patient partner engagement, and co-design approaches yielded rich research outputs., Conclusions: Collaboration between research teams and Patient Engagement Teams can promote effective patient engagement through a PAC. Deliberate and flexible strategies are needed to manage the PAC to create an ecology of Inclusiveness, Support, Mutual Respect, and Co-Build for meaningful patient engagement., Patient or Public Contribution: Patient research partners were involved in the decision to write this manuscript and collaborated equitably in the conception and development of this manuscript, including providing critical feedback. Patient research partners were active members of the PAC and informed the research project design, participant recruitment strategies, data collection and analysis, and will be involved in the implementation and dissemination of results. They are currently involved in the co-development of a patient engagement strategy using a Human-Centered Design process., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Indiscriminate use of laboratory blood testing in hospitals contributes to patient discomfort and healthcare waste. Patient engagement in low-value healthcare can help reduce overuse. Understanding patient experience is necessary to identify opportunities to improve patient engagement with in-hospital laboratory testing., Objectives: To understand patient experience with the process of in-hospital laboratory blood testing., Methods: We used a qualitative study design via semistructured interviews conducted online or over the phone. Participants were adult patients or family members/caregivers (≥18 years of age) with a recent (within 12 months of interview) experience of hospitalization in Alberta or British Columbia, Canada. We identified participants through convenience sampling and conducted interviews between May 2021 and June 2022. We analysed transcripts using thematic content analysis. Recruitment was continued until code saturation was reached., Results: We interviewed 16 participants (13 patients, 1 family member and 2 caregivers). We identified four themes from patients' experiences of in-hospital laboratory blood testing: (i) patients need information from healthcare teams about expected blood testing processes, (ii) blood draw processes should consider patient comfort and preferences, (iii) patients want information from their healthcare teams about the rationale and frequency of blood testing and (iv) patients need information on how their testing results affect their medical care., Conclusion: Current laboratory testing processes in hospitals do not facilitate shared decision-making and patient engagement. Patient engagement with laboratory testing in hospitals requires an empathetic healthcare team that provides clear communication regarding testing procedures, rationale and results, while considering patient preferences and offering opportunities for involvement., Patient or Public Contribution: We interviewed 16 patients and/or family members/caregivers regarding their in-hospital laboratory blood testing experiences. Our findings show correlations between patient needs and patient recommendations to make testing processes more patient-centred. To bring a lived-experience lens to this study, we formed a Patient Advisory Council with 9-11 patient research partners. Our patient research partners informed the research design, co-developed participant recruitment strategies, co-conducted data collection and informed the data analysis. Some of our patient research partners are co-authors of this manuscript., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Squeezed light is injected into the dark port of gravitational wave interferometers, in order to reduce the quantum noise. A fraction of the interferometer output light can reach the OPO due to sub-optimal isolation of the squeezing injection path. This backscattered light interacts with squeezed light generation process, introducing additional measurement noise. We present a theoretical description of the noise coupling mechanism and we prove the model with experimental results. We propose a control scheme to achieve a de-amplification of the backscattered light inside the OPO with a consequent reduction of the noise caused by it. The scheme was implemented at the GEO 600 detector and has proven to be crucial in maintaining a good level of quantum noise reduction of the interferometer for high parametric gain of the OPO. In particular, the mitigation of the backscattered light noise helped in reaching 6 dB of quantum noise reduction [Phys. Rev. Lett.126, 041102 (2021)10.1103/PhysRevLett.126.041102]. We show that the impact of backscattered-light-induced noise on the squeezing performance is phenomenologically equivalent to increased phase noise of the squeezing angle control. The results discussed in this paper provide a way for a more accurate estimation of the residual phase noise of the squeezed light field. Finally, the knowledge of the backscattered light noise coupling mechanism is a useful tool to inform the design of the squeezing injection path in terms of path stability and optical isolation.

Longer wavelength lasers will be needed for future gravitational wave detectors that use cryogenic cooling of silicon based test-mass optics. Diode lasers with a 1550 nm wavelength output are potential seed light sources for such a detector, however diode laser devices have a different spectral profile and higher frequency noise than the solid state lasers used in current detectors. We present a frequency stabilisation system for a 1550 nm external cavity diode laser capable of reducing the laser frequency noise to a level of 0.1HzHz up to 1 kHz with a unity gain frequency of 535 kHz using a hybrid analogue-digital servo with in-loop cancellation of resonant features. In addition, a method of high speed digital filter optimisation and automated design is demonstrated.

Photon shot noise, arising from the quantum-mechanical nature of the light, currently limits the sensitivity of all the gravitational wave observatories at frequencies above one kilohertz. We report a successful application of squeezed vacuum states of light at the GEO 600 observatory and demonstrate for the first time a reduction of quantum noise up to 6.03±0.02  dB in a kilometer scale interferometer. This is equivalent at high frequencies to increasing the laser power circulating in the interferometer by a factor of 4. Achieving this milestone, a key goal for the upgrades of the advanced detectors required a better understanding of the noise sources and losses and implementation of robust control schemes to mitigate their contributions. In particular, we address the optical losses from beam propagation, phase noise from the squeezing ellipse, and backscattered light from the squeezed light source. The expertise gained from this work carried out at GEO 600 provides insight toward the implementation of 10 dB of squeezing envisioned for third-generation gravitational wave detectors.

This study examined the ability of dental students and qualified dentists to visually assess the total occlusal convergence of clinical crowns. 10 working casts of maxillary molar crown preparations were installed in phantom heads in a clinical skills laboratory. 87 participants assessed the buccolingual and mesiodistal total occlusal convergence of the casts. 2nd-year students with no experience in fixed prosthodontics served as a control group with 3rd, 4th and 5th-year students and qualified dentists including specialists in restorative dentistry involved. Differences were calculated between the measured angles and the subject's estimate to assess accuracy. For 8 of the 20 surfaces measured there were significant differences. (p ⟨ 0.05). Differences were not standardized between the groups, with no clear patterns of difference in tooth type or aspect assessed. Differences were primarily between the control group and the more experienced groups. The remaining groups were of similar ability. A minority of participants in each group were highly divergent from their peers. This study found significant differences between participants with no experience of fixed prosthodontics and those with experience, however, the ability to assess total occlusal convergence does not appear to improve significantly with experience., (Copyright© 2020 Dennis Barber Ltd.)

Objective There is growing emphasis on health care organizations to ensure that lay people are meaningfully engaged as partners on research teams. Our aim was to explore the perspectives of patients, family members and informal caregivers who have been involved on health care research teams in Canada and elicit their recommendations for meaningful engagement. Methods We conducted a qualitative study guided by thematic analysis of transcripts of focus groups and interviews of 19 experienced patient research partners in Canada. Results We identified four main themes: research environment, expectations, support and value, which highlight participants' combined perspectives on important factors to ensure their engagement in research is meaningful. Conclusions Our findings add to the evolving evidence base on the perspectives of lay people involved in health care research and their recommendations for research leaders on meaningful engagement. Our study suggests that research leaders should provide a welcoming research environment, outline appropriate expectations for patient research partners on research teams, support patient research partners' engagement in projects and recognize the value patient research partners bring to health research.

The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two "subunit" type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the Mycobacterium tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each "vaccine" tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Several km-scale gravitational-wave detectors have been constructed world wide. These instruments combine a number of advanced technologies to push the limits of precision length measurement. The core devices are laser interferometers of a new kind; developed from the classical Michelson topology these interferometers integrate additional optical elements, which significantly change the properties of the optical system. Much of the design and analysis of these laser interferometers can be performed using well-known classical optical techniques, however, the complex optical layouts provide a new challenge. In this review we give a textbook-style introduction to the optical science required for the understanding of modern gravitational wave detectors, as well as other high-precision laser interferometers. In addition, we provide a number of examples for a freely available interferometer simulation software and encourage the reader to use these examples to gain hands-on experience with the discussed optical methods.

Expression of the PMLRARalpha fusion dominant-negative oncogene in the epidermis of transgenic mice resulted in spontaneous skin tumors attributed to changes in both the PML and RAR pathways [Hansen et al., Cancer Res 2003; 63:5257-5265]. To determine the contribution of PML to skin tumor susceptibility, transgenic mice were generated on an FVB/N background, that overexpressed the human PML protein in epidermis and hair follicles under the control of the bovine keratin 5 promoter. PML was highly expressed in the epidermis and hair follicles of these mice and was also increased in cultured keratinocytes where it was confined to nuclear bodies. While an overt skin phenotype was not detected in young transgenic mice, expression of keratin 10 (K10) was increased in epidermis and hair follicles and cultured keratinocytes. As mice aged, they exhibited extensive alopecia that was accentuated on the C57BL/6J background. Following skin tumor induction with 7, 12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, papilloma multiplicity and size were decreased in the transgenic mice by 35%, and the conversion of papillomas to carcinomas was delayed. Cultured transgenic keratinocytes underwent premature senescence and upregulated transcripts for p16 and Rb but not p19 and p53. Together, these changes suggest that PML participates in regulating the growth and differentiation of keratinocytes that likely influence its activity as a suppressor for tumor development.

Low-absorption optics made of OH-reduced fused silica are a key technology for future gravitational wave detectors such as the Advanced LIGO. We developed a sensitive method to measure the absorption inside the beam splitter of the GEO 600, taking advantage of the effect of thermal lensing. Using this method, we derived a bulk absorption of less than 0.25 ppm/cm for a piece of Suprasil 311 SV at a wavelength of 1064 nm. To the best of our knowledge, this is the lowest value of light absorption inside fused silica reported so far in the literature.

The construction of transgenic FVB/N mice targeting the PMLRARA fusion gene under the control of a human MRP8 promoter recapitulated the phenotype of acute promyelocytic leukemia but had the unexpected result of multiple squamous papillomas of the skin (Brown et al., PROC: Natl. Acad. Sci. USA, 94:2551-2556, 1997). In addition, transgenic MRP8-PMLRARA mice exhibited a skin phenotype characteristic of vitamin A deficiency. The severity of the skin phenotype and spontaneous papilloma development correlated with the level of transgene expression. Papilloma formation was preceded by follicular hyperplasia and the expression of epidermal differentiation markers in the follicular epithelium. Mutations in the Ha or Ki alleles of ras were not detected in papillomas that developed on transgenic skin, and papilloma formation was accentuated on the C57/Bl6 background, unlike the usual resistance of this strain to skin tumor induction. Analysis of liver extracts from transgenic mice indicated a deficiency in the production of retinoic acid. Furthermore, affected transgenic epidermis had reduced levels of retinoic acid receptoralpha (RARalpha) and retinoic X receptor (RXRalpha), and supplementation with exogenous retinoic acid prevented the skin phenotype. When transgenic keratinocytes were grafted to nude mice, the resulting integument was normal, and conversely, when transgenic bone marrow was grafted to normal mice, a skin phenotype did not develop. Together these results suggest that local interruption of PML and RARalpha signaling in the skin, together with a systemic retinoid deficiency, initiates a tumor induction pathway that is independent of ras activation.

Previous studies using keratinocytes from epidermal growth factor receptor (EGFR)-deficient mice revealed that the EGFR is not required for papilloma formation initiated by a mutant rasHa gene, although the tumors that develop are very small (A. A. Dlugosz et aL, Cancer Res., 57: 3180-3188, 1997). The current study used a combination of bromodeoxyuridine pulse-chase, proliferating cell nuclear antigen distribution, and differentiation marker analysis to reveal the following: (a) the EGFR was required to maintain the proliferative population in the basal cell compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells migrated into the suprabasal compartment and initiated the differentiation program prematurely; and (c) these changes were associated with cell cycle arrest. Further analysis of v-rasHa-transformed EGFR-deficient keratinocytes in vitro indicated that such cells migrated more on and attached less to extracellular matrix components. Together, these studies reveal that an essential function for the EGFR pathway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation.