Reclaiming Agency in Care Decisions and Barriers From the Perspectives of Individuals With Acquired Brain Injury and Their Family Members.

BACKGROUND: The ability to self-advocate or have a say in one's care is integral to personalised care after acquired brain injury (ABI). This study aimed to understand what constitutes self-advocacy and associated barriers and facilitators throughout hospital transitions and into the community. METHOD: Qualitative methodology was employed with semistructured interviews conducted with 12 people with ABI and 13 family members. Interviews were conducted at predischarge (in-person or via telephone) and 4 months postdischarge (via telephone) from the brain injury rehabilitation unit of a tertiary hospital. Data were thematically analysed using a hybrid deductive-inductive approach. RESULTS: Self-advocacy reflects the process of reclaiming agency or people's efforts to exert influence over care decisions after ABI. Agency varies along a continuum, often beginning with impaired processing of the self or environment (loss of agency) before individuals start to understand and question their care (emerging agency) and ultimately plan and direct their ongoing and future care (striving for agency). This process may vary across individuals and contexts. Barriers to self-advocacy for individuals with ABI include neurocognitive deficits that limit capacity and desire for control over decisions, unfamiliar and highly structured environments and lack of family support. Facilitators include neurocognitive recovery, growing desire to self-advocate and scaffolded support from family and clinicians. CONCLUSION: Self-advocacy after ABI entails a process of reclaiming agency whereby individuals seek to understand, question and direct their ongoing care. This is facilitated by neurocognitive recovery, growing capacity and desire and scaffolded supports. Research evaluating approaches for embedding self-advocacy skills early in brain injury rehabilitation is recommended. PATIENT OR PUBLIC CONTRIBUTION: Two caregivers with lived experience of supporting a family member with ABI were involved in the design and conduct of this study and contributed to and provided feedback on the manuscript.

One size doesn't fit all: methodological reflections in conducting community-based behavioural science research to tailor COVID-19 vaccination initiatives for public health priority populations.

BACKGROUND: Promoting the uptake of vaccination for infectious diseases such as COVID-19 remains a global challenge, necessitating collaborative efforts between public health units (PHUs) and communities. Applied behavioural science can play a crucial role in supporting PHUs' response by providing insights into human behaviour and informing tailored strategies to enhance vaccination uptake. Community engagement can help broaden the reach of behavioural science research by involving a more diverse range of populations and ensuring that strategies better represent the needs of specific communities. We developed and applied an approach to conducting community-based behavioural science research with ethnically and socioeconomically diverse populations to guide PHUs in tailoring their strategies to promote COVID-19 vaccination. This paper presents the community engagement methodology and the lessons learned in applying the methodology. METHODS: The community engagement methodology was developed based on integrated knowledge translation (iKT) and community-based participatory research (CBPR) principles. The study involved collaboration with PHUs and local communities in Ontario, Canada to identify priority groups for COVID-19 vaccination, understand factors influencing vaccine uptake and co-design strategies tailored to each community to promote vaccination. Community engagement was conducted across three large urban regions with individuals from Eastern European communities, African, Black, and Caribbean communities and low socioeconomic neighbourhoods. RESULTS: We developed and applied a seven-step methodology for conducting community-based behavioural science research: (1) aligning goals with system-level partners; (2) engaging with PHUs to understand priorities; (3) understanding community strengths and dynamics; (4) building relationships with each community; (5) establishing partnerships (community advisory groups); (6) involving community members in the research process; and (7) feeding back and interpreting research findings. Research partnerships were successfully established with members of prioritized communities, enabling recruitment of participants for theory-informed behavioural science interviews, interpretation of findings, and co-design of targeted recommendations for each PHU to improve COVID-19 vaccination uptake. Lessons learned include the importance of cultural sensitivity and awareness of sociopolitical context in tailoring community engagement, being agile to address the diverse and evolving priorities of PHUs, and building trust to achieve effective community engagement. CONCLUSION: Effective community engagement in behavioural science research can lead to more inclusive and representative research. The community engagement approach developed and applied in this study acknowledges the diversity of communities, recognizes the central role of PHUs, and can help in addressing complex public health challenges.

MicroLED light source for optical sectioning structured illumination microscopy.

Optical sectioning structured illumination microscopy (OS-SIM) provides optical sectioning capability in wide-field microscopy. The required illumination patterns have traditionally been generated using spatial light modulators (SLM), laser interference patterns, or digital micromirror devices (DMDs) which are too complex to implement in miniscope systems. MicroLEDs have emerged as an alternative light source for patterned illumination due to their extreme brightness capability and small emitter sizes. This paper presents a directly addressable striped microLED microdisplay with 100 rows on a flexible cable (70 cm long) for use as an OS-SIM light source in a benchtop setup. The overall design of the microdisplay is described in detail with luminance-current-voltage characterization. OS-SIM implementation with a benchtop setup shows the optical sectioning capability of the system by imaging within a 500 µm thick fixed brain slice from a transgenic mouse where oligodendrocytes are labeled with a green fluorescent protein (GFP). Results show improved contrast in reconstructed optically sectioned images of 86.92% (OS-SIM) compared with 44.31% (pseudo-widefield). MicroLED based OS-SIM therefore offers a new capability for deep tissue widefield imaging.

Navigating imperfect policies to donate plasma: Survey on plasma donation and a pilot plasma donation program among men who have sex with men in Canada.

BACKGROUND: In 2021, Canada implemented a pilot plasma program allowing some sexually active men who have sex with men (including but not limited to gay and bisexual men; gbMSM) to donate plasma. Changes to plasma donation policy could help address inequities in access to plasma donation and increase Canada's domestically collected plasma supply if more gbMSM donate as a result. We aimed to (1) examine views regarding plasma donation and the pilot program prior to implementation and (2) identify modifiable theory-informed predictors of gbMSM's intention to donate plasma. METHODS: We developed, piloted, and disseminated a questionnaire informed by the Theoretical Domains Framework (TDF). We recruited gbMSM in London (ON) and Calgary (AB) to an anonymous, online cross-sectional survey. RESULTS: A total of 246 gbMSM completed the survey. On scales from 1 (strongly disagree) to 5 (strongly agree), general intention to donate was high (mean = 4.24; SD = 0.94). The pilot program itself was mostly acceptable (mean = 3.71, SD = 1.16), but the intention to donate under the unique requirements of the pilot program was lower than general intention (mean = 3.58; SD = 1.26). Two domains from the theoretical domains framework (TDF) (beliefs about consequences of donating plasma and social influences) were independently associated with general intention to donate. DISCUSSION: The pilot plasma program as an incremental step toward more inclusive policies was mostly viewed as acceptable by the impacted communities. Historical and ongoing exclusions create unique barriers to donation. There are clear opportunities for developing theory-informed interventions to support gbMSM to donate plasma as policies continue to become more inclusive and more become eligible to donate.

Leveraging community health workers as vaccinators: a case study exploring the role of Malawi's Health Surveillance Assistants in delivering routine immunization services.

BACKGROUND: Global chronic health worker shortages and stagnating routine immunization rates require new strategies to increase vaccination coverage and equity. As trained, trusted members of their local communities, community health workers (CHWs) are in a prime position to expand the immunization workforce and increase vaccination coverage in under-reached communities. Malawi is one of only a few countries that relies on CHWs-called Health Surveillance Assistants (HSAs) in Malawi-to administer routine immunizations, and as such offers a unique example of how this can be done. CASE PRESENTATION: We sought to describe the operational and programmatic characteristics of a functional CHW-led routine immunization program by conducting interviews with HSAs, HSA supervisors, ministry of health officials, and community members in Malawi. This case study describes how and where HSAs provide vaccinations, their vaccination-related responsibilities, training and supervision processes, vaccine safety considerations, and the community-level vaccine supply chain. Interview participants consistently described HSAs as a high-functioning vaccination cadre, skilled and dedicated to increasing vaccine access for children. They also noted a need to strengthen some aspects of professional support for HSAs, particularly related to training, supervision, and supply chain processes. Interviewees agreed that other countries should consider following Malawi's example and use CHWs to administer vaccines, provided they can be sufficiently trained and supported. CONCLUSIONS: This account from Malawi provides an example of how a CHW-led vaccination program operates. Leveraging CHWs as vaccinators is a promising yet under-explored task-shifting approach that shows potential to help countries maximize their health workforce, increase vaccination coverage and reach more zero-dose children. However, more research is needed to produce evidence on the impact of leveraging CHWs as vaccinators on patient safety, immunization coverage/vaccine equity, and cost-effectiveness as compared to use of other cadres for routine immunization.

Improved access yet inequitable experience: gay, bisexual and other men who have sex with men's views of more inclusive criteria for source plasma donation.

BACKGROUND: Canada has incrementally reduced restrictions to blood and plasma donation that impact men who have sex with men, gay, bisexual, and queer men, and some Two Spirit, transgender and non-binary individuals (MSM/2SGBTQ+). Prior to the launch of a pilot program in 2021 enabling some MSM/2SGBTQ + to donate source plasma, we explored the acceptability of the program among individuals who could become eligible to donate in the program. METHODS: We invited men identifying as MSM/2SGBTQ + to participate in two consecutive semi-structured interviews to explore their views on blood and plasma donation policy, plasma donation, and the proposed Canadian plasma donation program. Interview transcripts were analyzed thematically and acceptability-related themes were mapped onto the Theoretical Framework of Acceptability. RESULTS: Twenty-seven men identifying as having sex with men participated in 53 interviews. Eighteen themes were mapped onto the seven construct domains of the Theoretical Framework of Acceptability. Underlying all aspects of acceptability was a tension between four primary values influencing participants' views: altruism, equity, supply sufficiency, and evidence-based policy. The program was viewed as welcome progress on a discriminatory policy, with many excited to participate, yet tension with inequitable aspects of the program undermined support for the program and interest to contribute to it. The high demands of the program are unique for MSM/2SGBTQ + and are only tolerable as part of a program that is an incremental and instrumental step to more equitable donation policies. CONCLUSION: Findings highlight past experiences of exclusion in Canada as a unique and critical part of the context of the donation experience among MSM/2SGBTQ+. Despite the program's goals of greater inclusivity of MSM/2SGBTQ + individuals, the anticipated experience of the program included continued stigmatization and inequities. Future research should seek to understand the experienced views of MSM/2SGBTQ + donors to ensure that as policies change, policies are implemented equitably.

Staff perspectives on barriers and enablers to implementing alternative source plasma eligibility criteria for gay, bisexual, and other men who have sex with men.

BACKGROUND: Canadian Blood Services introduced new eligibility criteria that allows some sexually active gay, bisexual, and other men who have sex with men (gbMSM) to donate source plasma, marking a significant change from time-based deferral criteria. We aimed to identify potential barriers and enablers to implementing the new criteria from the perspective of donor center staff. STUDY DESIGN AND METHODS: We conducted Theoretical Domains Framework-informed interviews with staff from two source plasma donation centers in Canada. RESULTS: We completed 28 interviews between June 2020 and April 2021. Three themes representing eight domains captured key tensions. Valuing inclusive eligibility criteria: staff support inclusive criteria; many were concerned the new criteria remained discriminatory. Investing in positive donor experiences: staff wished to foster positive donor experiences; however, they worried gbMSM donors would express anger and disappointment regarding the new criteria, staff would experience unease over using stigmatizing criteria and convey nonverbal cues of discomfort, and recurring plasma donors may behave inappropriately. Supporting education, training, and transparency of eligibility criteria: participants believed providing in-person training (i.e., to explain criteria rationale, address discomfort, practice responding to donor questions) and ensuring donors and the public were well-informed of the upcoming changes would improve implementation. DISCUSSION: Participant views emphasize the importance of supporting staff through training and transparent communication to optimize the delivery of world-class equitable care for a new cohort of donors who have previously been excluded from plasma donation. Findings inform which staff supports to consider to improve implementation as policies continue to shift internationally.

Coping or adapting? Experiences of food and nutrition insecurity in specialised fishing households in Komodo District, eastern Indonesia.

BACKGROUND: There is growing recognition of the need for fish to be better integrated into nutrition-sensitive strategies for addressing malnutrition. Fish are overwhelmingly produced by the small-scale sector, which supports food and nutrition security directly through the provision of fish and indirectly through the generation of income which can be used to purchase other desired foods. However, there has been relatively little research on the extent of food and nutrition security in specialised fishing communities. This study assessed food and nutrition security among households in specialised fishing communities in Komodo District, eastern Indonesia. METHODS: We assessed the seasonal nutrition quality of household diets using the Food Consumption Score for nutritional analysis and food insecurity using the Household Food Insecurity Access Scale in 66 households across three communities, using a modified cluster sampling strategy. We calculated and generated descriptive statistics for these indicators with Microsoft Excel and ran a logistic generalized linear mixed model to determine factors associated with severe food insecurity using SPSS. We used semi-structured interviews and focus group discussions to understand perceptions of, change over time, and strategies for dealing with food shortfalls. RESULTS: While most households have acceptable access to nutritious foods, especially protein and heme iron-rich foods, nearly one half of households consumed vitamin A rich foods on less than 3 days of the 7-day recall period in either season. More than half of households reported experiencing a moderate or severe level of food insecurity, with higher food insecurity in the wet season. Low maternal education (OR: 3.8, 95%CI 1.5-9.9) and lower household wealth (OR: 0.5, 95%CI 0.3-0.9) were found to be associated with a severe level of food insecurity. Household's consumptive and non-consumptive response strategies reflect adaptation to chronic food insecurity but are nutritionally and economically unsustainable. CONCLUSION: Households in specialised fishing communities in Komodo District consumed diets with low diversity and experienced high levels of food insecurity. There is a need for culturally-appropriate nutrition-sensitive strategies to enhance food and nutrition security in vulnerable fishing communities.

Optimization of Blood Handling and Peripheral Blood Mononuclear Cell Cryopreservation of Low Cell Number Samples.

BACKGROUND: Rural/remote blood collection can cause delays in processing, reducing PBMC number, viability, cell composition and function. To mitigate these impacts, blood was stored at 4 °C prior to processing. Viable cell number, viability, immune phenotype, and Interferon-γ (IFN-γ) release were measured. Furthermore, the lowest protective volume of cryopreservation media and cell concentration was investigated. METHODS: Blood from 10 individuals was stored for up to 10 days. Flow cytometry and IFN-γ ELISPOT were used to measure immune phenotype and function on thawed PBMC. Additionally, PBMC were cryopreserved in volumes ranging from 500 µL to 25 µL and concentration from 10 × 106 cells/mL to 1.67 × 106 cells/mL. RESULTS: PBMC viability and viable cell number significantly reduced over time compared with samples processed immediately, except when stored for 24 h at RT. Monocytes and NK cells significantly reduced over time regardless of storage temperature. Samples with >24 h of RT storage had an increased proportion in Low-Density Neutrophils and T cells compared with samples stored at 4 °C. IFN-γ release was reduced after 24 h of storage, however not in samples stored at 4 °C for >24 h. The lowest protective volume identified was 150 µL with the lowest density of 6.67 × 106 cells/mL. CONCLUSION: A sample delay of 24 h at RT does not impact the viability and total viable cell numbers. When long-term delays exist (>4 d) total viable cell number and cell viability losses are reduced in samples stored at 4 °C. Immune phenotype and function are slightly altered after 24 h of storage, further impacts of storage are reduced in samples stored at 4 °C.

Subcellular Localization and Activity of the Mitogen-Activated Protein Kinase Kinase 7 (MKK7) γ Isoform are Regulated through Binding to the Phosphatase Calcineurin.

Calcineurin (CaN) phosphatase signaling is regulated by targeting CaN to substrates, inhibitors, and scaffold proteins containing docking motifs with the consensus sequence of PxIxIT. Here, we identify the docking of CaN to the γ isoform of MKK7, a component of the c-Jun N-terminal kinase (JNK) pathway. Because of alternative splicing of a single exon within the N-terminal domain, MKK7γ encodes a unique PxIxIT motif (PIIVIT) that is not present in MKK7α or ß We found that MKK7γ bound directly to CaN through this PIIVIT motif in vitro, immunoprecipitated with CaN from cell extracts, and exhibited fluorescence resonance energy transfer (FRET) with CaN in the cytoplasm but not in the nucleus of living cells. In contrast, MKK7α and ß exhibited no direct binding or FRET with CaN and were localized more in the nucleus than the cytoplasm. Furthermore, the inhibition of CaN phosphatase activity increased the basal phosphorylation of MKK7γ but not MKK7ß Deletion of the MKK7γ PIIVIT motif eliminated FRET with CaN and promoted MKK7γ redistribution to the nucleus; however, the inhibition of CaN activity did not alter MKK7γ localization, indicating that MKK7γ cytoplasmic retention by CaN is phosphatase activity independent. Finally, the inhibition of CaN phosphatase activity in vascular smooth muscle cells, which express MKK7γ mRNA, enhances JNK activation. Overall, we conclude that the MKK7γ-specific PxIxIT motif promotes high-affinity CaN binding that could promote novel cross talk between CaN and JNK signaling by limiting MKK7γ phosphorylation and restricting its localization to the cytoplasm.

Determining the Spatial Relationship of Membrane-Bound Aquaporin-4 Autoantibodies by STED Nanoscopy.

Determining the spatial relationship of individual proteins in dense assemblies remains a challenge for superresolution nanoscopy. The organization of aquaporin-4 (AQP4) into large plasma membrane assemblies provides an opportunity to image membrane-bound AQP4 antibodies (AQP4-IgG) and evaluate changes in their spatial distribution due to alterations in AQP4 isoform expression and AQP4-IgG epitope specificity. Using stimulated emission depletion nanoscopy, we imaged secondary antibody labeling of monoclonal AQP4-IgGs with differing epitope specificity bound to isolated tetramers (M1-AQP4) and large orthogonal arrays of AQP4 (M23-AQP4). Imaging secondary antibodies bound to M1-AQP4 allowed us to infer the size of individual AQP4-IgG binding events. This information was used to model the assembly of larger AQP4-IgG complexes on M23-AQP4 arrays. A scoring algorithm was generated from these models to characterize the spatial arrangement of bound AQP4-IgG antibodies, yielding multiple epitope-specific patterns of bound antibodies on M23-AQP4 arrays. Our results delineate an approach to infer spatial relationships within protein arrays using stimulated emission depletion nanoscopy, offering insight into how information on single antibody fluorescence events can be used to extract information from dense protein assemblies under a biologic context.

Local and Use-Dependent Effects of ß-Amyloid Oligomers on NMDA Receptor Function Revealed by Optical Quantal Analysis.

Beta amyloid (Aß) triggers the elimination of excitatory synaptic connections in the CNS, an early manifestation of Alzheimer's disease. Oligomeric assemblies of Aß peptide associate with excitatory synapses resulting in synapse elimination through a process that requires NMDA-type glutamate receptor activation. Whether Aß affects synaptic NMDA receptor (NMDAR) function directly and acts locally at synapses to which it has bound and whether synaptic activity influences Aß synaptic binding and synaptotoxicity have remained fundamental questions. Here, we used subcellular Ca2+ imaging in rat hippocampal neurons to visualize NMDAR function at individual synapses before and after Aß application. Aß triggered a robust impairment of NMDAR Ca2+ entry at most, but not all, synapses. NMDAR function was more severely impaired at highly active synapses and synapses with bound Aß, but activity was not required for Aß synapse binding. Blocking NMDARs during Aß exposure prevented Aß-mediated impairment. Finally, Aß impaired NMDAR Ca2+ entry at doses much lower than those required for NMDAR internalization, revealing a novel, potent mode of NMDAR regulation by Aß. SIGNIFICANCE STATEMENT: Amyloid ß (Aß) is strongly implicated in Alzheimer's disease. Aß triggers the elimination of excitatory synapses through a mechanism that requires NMDA receptors (NMDARs). However, little is known about how or whether Aß influences synaptic NMDAR function. We used an imaging-based assay to investigate the relationship among Aß binding, activity, and NMDAR function at individual synapses. Aß triggered a robust impairment of NMDAR Ca2+ entry at most, but not all, synapses. NMDAR function was more severely impaired at highly active synapses and synapses with bound Aß. Blocking NMDARs during Aß exposure prevented Aß-mediated impairment. Together, our experiments reveal a novel use-dependent, potent, and local mode of Aß-mediated NMDAR impairment.

Statistical performance of image cytometry for DNA, lipids, cytokeratin, & CD45 in a model system for circulation tumor cell detection.

Detection of circulating tumor cells (CTCs) in a blood sample is limited by the sensitivity and specificity of the biomarker panel used to identify CTCs over other blood cells. In this work, we present Bayesian theory that shows how test sensitivity and specificity set the rarity of cell that a test can detect. We perform our calculation of sensitivity and specificity on our image cytometry biomarker panel by testing on pure disease positive (D+ ) populations (MCF7 cells) and pure disease negative populations (D- ) (leukocytes). In this system, we performed multi-channel confocal fluorescence microscopy to image biomarkers of DNA, lipids, CD45, and Cytokeratin. Using custom software, we segmented our confocal images into regions of interest consisting of individual cells and computed the image metrics of total signal, second spatial moment, spatial frequency second moment, and the product of the spatial-spatial frequency moments. We present our analysis of these 16 features. The best performing of the 16 features produced an average separation of three standard deviations between D+ and D- and an average detectable rarity of ∼1 in 200. We performed multivariable regression and feature selection to combine multiple features for increased performance and showed an average separation of seven standard deviations between the D+ and D- populations making our average detectable rarity of ∼1 in 480. Histograms and receiver operating characteristics (ROC) curves for these features and regressions are presented. We conclude that simple regression analysis holds promise to further improve the separation of rare cells in cytometry applications. © 2017 International Society for Advancement of Cytometry.

Numerical analysis of wavefront aberration correction using multielectrode electrowetting-based devices.

We present numerical simulations of multielectrode electrowetting devices used in a novel optical design to correct wavefront aberration. Our optical system consists of two multielectrode devices, preceded by a single fixed lens. The multielectrode elements function as adaptive optical devices that can be used to correct aberrations inherent in many imaging setups, biological samples, and the atmosphere. We are able to accurately simulate the liquid-liquid interface shape using computational fluid dynamics. Ray tracing analysis of these surfaces shows clear evidence of aberration correction. To demonstrate the strength of our design, we studied three different input aberrations mixtures that include astigmatism, coma, trefoil, and additional higher order aberration terms, with amplitudes as large as one wave at 633 nm.

Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid ß-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aß) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aß(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aß-induced synaptic dysfunction, but we recently found that Aß(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aß(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aß, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aß(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aß(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0µM Aß(1-42) or 1-5µM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aßon LTP and synapse loss, suggesting that Aßinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

Verbal Initiation, Suppression, and Strategy Use and the Relationship with Clinical Symptoms in Schizophrenia.

OBJECTIVES: Individuals with schizophrenia have difficulties on measures of executive functioning such as initiation and suppression of responses and strategy development and implementation. The current study thoroughly examines performance on the Hayling Sentence Completion Test (HSCT) in individuals with schizophrenia, introducing novel analyses based on initiation errors and strategy use, and association with lifetime clinical symptoms. METHODS: The HSCT was administered to individuals with schizophrenia (N=77) and age- and sex-matched healthy controls (N=45), along with background cognitive tests. The standard HSCT clinical measures (initiation response time, suppression response time, suppression errors), composite initiation and suppression error scores, and strategy-based responses were calculated. Lifetime clinical symptoms [formal thought disorder (FTD), positive, negative] were calculated using the Lifetime Dimensions of Psychosis Scale. RESULTS: After controlling for baseline cognitive differences, individuals with schizophrenia were significantly impaired on the suppression response time and suppression error scales. For the novel analyses, individuals with schizophrenia produced a greater number of initiation errors and subtly wrong errors, and produced fewer responses indicative of developing an appropriate strategy. Strategy use was negatively correlated with FTD symptoms in individuals with schizophrenia. CONCLUSIONS: The current study provides further evidence for deficits in the initiation and suppression of verbal responses in individuals with schizophrenia. Moreover, an inability to attain a strategy at least partly contributes to increased semantically connected errors when attempting to suppress responses. The association between strategy use and FTD points to the involvement of executive deficits in disorganized speech in schizophrenia. (JINS, 2016, 22, 735-743).

Miniaturized fiber-coupled confocal fluorescence microscope with an electrowetting variable focus lens using no moving parts.

We report a miniature, lightweight fiber-coupled confocal fluorescence microscope that incorporates an electrowetting variable focus lens to provide axial scanning for full three-dimensional (3D) imaging. Lateral scanning is accomplished by coupling our device to a laser-scanning confocal microscope through a coherent imaging fiber-bundle. The optical components of the device are combined in a custom 3D-printed adapter with an assembled weight of <2 g that can be mounted onto the head of a mouse. Confocal sectioning provides an axial resolution of ∼12 µm and an axial scan range of ∼80 µm. The lateral field-of-view is 300 µm, and the lateral resolution is 1.8 µm. We determined these parameters by imaging fixed sections of mouse neuronal tissue labeled with green fluorescent protein (GFP) and fluorescent bead samples in agarose gel. To demonstrate viability for imaging intact tissue, we resolved multiple optical sections of ex vivo mouse olfactory nerve fibers expressing yellow fluorescent protein (YFP).

Introduction to the Optics and the Brain 2023 feature issue.

A feature issue is being presented by a team of guest editors containing papers based on contributed submissions including studies presented at Optics and the Brain, held April 24-27, 2023 as part of Optica Biophotonics Congress: Optics in the Life Sciences, in Vancouver, Canada.

Hayling and stroop tests tap dissociable deficits and network-level neural correlates.

Although many executive function screens have been developed, it is not yet clear whether these assessments are equally effective in detecting post-stroke deficits of initiation and inhibition. This study presents a comparative analysis of the Stroop and Hayling tests aiming to evaluate whether these tests measure the same underlying cognitive functions and to identify the neural correlates of the deficits detected by both tasks. Sixty six stroke survivors and 70 healthy ageing controls completed the Hayling and Stroop tests. Stroke patients were found to exhibit qualitative performance differences across analogous Stroop and Hayling Test metrics intended to tap initiation and inhibition. The Stroop test was found to have high specificity to abnormal performance, but low sensitivity relative to the Hayling Test. Minimal overlap was present between the network-level correlates of analogous Stroop and Hayling Test metrics. Hayling Task strategy use metrics were significantly associated with distinct patterns of disconnection in stroke survivors, providing novel insight into the neural correlates of fine-grained behavioural patterns. Overall, these findings strongly suggest that the functions tapped by the Stroop and Hayling Test are both behaviourally and anatomically dissociable. The Hayling Test was found to offer improved sensitivity and detail relative to the Stroop test. This novel demonstration of the Hayling Test within the stroke population suggests that this task represents an effective measure for quantifying post-stroke initiation and inhibition deficits.

OpenSTED: open-source dynamic intensity minimum system for stimulated emission depletion microscopy.

Significance: Stimulated emission depletion (STED) is a powerful super-resolution microscopy technique that can be used for imaging live cells. However, the high STED laser powers can cause significant photobleaching and sample damage in sensitive biological samples. The dynamic intensity minimum (DyMIN) technique turns on the STED laser only in regions of the sample where there is fluorescence signal, thus saving significant sample photobleaching. The reduction in photobleaching allows higher resolution images to be obtained and longer time-lapse imaging of live samples. A stand-alone module to perform DyMIN is not available commercially. Aim: In this work, we developed an open-source design to implement three-step DyMIN on a STED microscope and demonstrated reduced photobleaching for timelapse imaging of beads, cells, and tissue. Approach: The DyMIN system uses a fast multiplexer circuit and inexpensive field-programmable gate array controlled by Labview software that operates as a stand-alone module for a STED microscope. All software and circuit diagrams are freely available. Results: We compared time-lapse images of bead samples using our custom DyMIN system to conventional STED and recorded a ∼ 46 % higher signal when using DyMIN after a 50-image sequence. We further demonstrated the DyMIN system for time-lapse STED imaging of live cells and brain tissue slices. Conclusions: Our open-source DyMIN system is an inexpensive add-on to a conventional STED microscope that can reduce photobleaching. The system can significantly improve signal to noise for dynamic time-lapse STED imaging of live samples.