OCTA Signal Quality Augmentation Using the Isometric Handgrip Test to Maximize Vascular Flow (SQUEEZE): A Randomized Crossover Trial.

Purpose: To determine if performing the isometric handgrip test (IHGT) can augment optical coherence tomography angiography (OCTA) vascular signal quality in eyes with macular abnormalities. Methods: A randomized, single-blinded crossover trial was conducted including 36 participants with macular abnormalities, randomized to undergo OCTA with or without the IHGT, then crossed over to the alternate "intervention" after 1 minute. The primary outcome was OCTA signal quality after 1 minute of squeezing at 50% maximum grip strength. Secondary outcomes were other measures of vascular flow and systemic blood pressure (BP), also regressed against person- and eye-level covariables. Results: Primary analysis of OCTA signal quality with versus without the IHGT was nonsignificant (P = 0.73). Nested analyses showed that the IHGT resulted in increased OCTA B-scan retinal vascular flow signal (2.95 [-1.64 to 7.55] Δ%, P < 0.05) and increased systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (4.94 [0.41 to 9.47] to 12.38 [8.01 to 16.75] mm Hg, P < 0.05). OCTA signal quality and en face vessel density and perfusion changes were associated with sex, refraction, race/ethnicity, and right-hand IHGT use (P < 0.05). Greater increases in systolic and diastolic BP and mean arterial pressure were generally associated with right-hand IHGT use and greater maximum grip strength (P < 0.09). Conclusions: The IHGT can temporarily increase OCTA B-scan retinal vascular flow signal in participants with macular abnormalities. IHGT-induced changes to systemic BP appear to be linked to absolute (rather than relative) grip strength, implying that the IHGT may be ineffective with low grip strength. Further research in larger populations is warranted. Translational Relevance: This study provides early validation that the IHGT may augment OCTA output, which may lead to improved noninvasive detection of pathologic vascular changes.

Retinal sensitivity changes in early/intermediate AMD: a systematic review and meta-analysis of visual field testing under mesopic and scotopic lighting.

Visual fields under mesopic and scotopic lighting are increasingly being used for macular functional assessment. This review evaluates its statistical significance and clinical relevance, and the optimal testing protocol for early/intermediate age-related macular degeneration (AMD). PubMed and Embase were searched from inception to 14/05/2022. All quality assessments were performed according to GRADE guidelines. The primary outcome was global mean sensitivity (MS), further meta-analysed by: AMD classification scheme, device, test pattern, mesopic/scotopic lighting, stimuli size/chromaticity, pupil dilation, testing radius (area), background luminance, adaptation time, AMD severity, reticular pseudodrusen presence, and follow-up visit. From 1489 studies screened, 42 observational study results contributed to the primary meta-analysis. Supported by moderate GRADE certainty of the evidence, global MS was significantly reduced across all devices under mesopic and scotopic lighting with large effect size (-0.9 [-1.04, -0.75] Hedge's g, P < 0.0001). The device (P < 0.01) and lighting (P < 0.05) used were the only modifiable factors affecting global MS, whereby the mesopic MP-1 and MAIA produced the largest effect sizes and exceeded test-retest variabilities. Global MS was significantly affected by AMD severity (intermediate versus early AMD; -0.58 [-0.88, -0.29] Hedge's g or -2.55 [3.62, -1.47] MAIA-dB) and at follow-up visit (versus baseline; -0.62 [-0.84, -0.41] Hedge's g or -1.61[-2.69, -0.54] MAIA-dB). Magnitudes of retinal sensitivity changes in early/intermediate AMD are clinically relevant for the MP-1 and MAIA devices under mesopic lighting within the central 10° radius. Other factors including pupil dilation and dark adaptation did not significantly affect global MS in early/intermediate AMD.

Immersive virtual reality in the treatment of auditory hallucinations: A PRISMA scoping review.

BACKGROUND: A large group of psychiatric patients suffer from auditory hallucinations (AH) despite relevant treatment regimens. In mental health populations, AH tend to be verbal (AVH) and the content critical or abusive. Trials employing immersive virtual reality (VR) to treat mental health disorders are emerging. OBJECTIVE: The aim of this scoping review is to provide an overview of clinical trials utilizing VR in the treatment of AH and to document knowledge gaps in the literature. METHODS: PubMed, Cochrane Library, and Embase were searched for studies reporting on the use of VR to target AH. RESULTS: 16 papers were included in this PRISMA scoping review (ScR). In most studies VR therapy (VRT) was employed to ameliorate treatment resistant AVH in schizophrenia spectrum disorders. Only two studies included patients with a diagnosis of affective disorders. The VRT was carried out with the use of an avatar to represent the patient's most dominant voice. DISCUSSION: The research field employing VR to treat AH is promising but still in its infancy. Results from larger randomized clinical trials are needed to establish substantial evidence of therapy effectiveness. Additionally, the knowledge base would benefit from more profound qualitative data exploring views of patients and therapists.

Design of a Workshop for Focused Transesophageal Echocardiography During Noncardiac Surgery in Nurse Anesthesia Education.

OBJECTIVE: The use of transesophageal echocardiography (TEE) by certified registered nurse anesthetists (CRNAs) during noncardiac surgery is relatively uncommon despite its unique potential to diagnose causes of hemodynamic instability. To address this problem, educational endeavors designed to provide practical TEE skills to CRNAs are needed. The aim of the current study was to evaluate the feasibility, acceptability, efficacy, and utility of a 2-day focused TEE workshop in nurse anesthesia education that employed a protocol involving a limited number of views and used goal-directed, qualitative assessments of critical physiologic parameters. METHODS: This was a prospective, observational study involving 14 second-year nurse anesthesia students. The cohort was evaluated following completion of this workshop by simulator-based testing involving hypothetical clinical scenarios, and this test data was analyzed according to the percent successful acquisition and interpretation of TEE views to determine immediate objective teaching efficacy. The acceptability, perceived efficacy, and perceived utility of the workshop were assessed by online survey, and survey responses were qualitative and quantitative in nature. RESULTS: Participants acquired appropriate TEE views associated with clinical scenarios 99% of the time and correctly interpreted the pathology in those views 93% of the time. Participants uniformly perceived significant educational value in this workshop and intend to incorporate TEE in their future clinical practice. CONCLUSIONS: A 2-day workshop to teach focused TEE to nurse anesthesia trainees directed by a streamlined protocol is feasible, acceptable, and perceived as useful by participants, and provides practical experience and entry-level competency in this point-of-care ultrasound modality.

A Systematic Review of the Effectiveness of Cervical Cancer Screening and Prevention Interventions for African American Women: Implications for Promoting Health Equity.

African American women suffer under the burden of cervical cancer as they are first in mortality, diagnosed at later stages, and have a survivorship rate that is lower than the national average. The aim of our review is to evaluate the effectiveness of cervical cancer screening and prevention interventions for African American women living in the United States and to assess their commitment to health equity. A literature search was conducted using PubMed, Embase, CINAHL, and Scopus using MeSH terms related to cervical cancer, human papillomavirus (HPV), screening and prevention, and African Americans. This resulted in 1970 articles. Studies were included if they promoted cervical screening or prevention, sampled African American women aged 18 and over, and evaluated interventions. Among the 23 articles that met inclusion criteria, there were a wide variety of intervention strategies, that is, community health workers, patient navigation, patient reminders, self-sampling collection, and HPV vaccination. Health education interventions, when coupled with patient navigation or community health workers, were effective in promoting screening participation (odds ratio: 2.43, 95% confidence interval: 1.47-4.02). There were mixed results regarding the incorporation of health equity principles. This review supports the importance of incorporating health equity principles and community based methods in screening and prevention interventions. Future research and practice should incorporate African American women's perspectives in intervention development and implementation.

Variability of oxygen requirements in critically ill COVID-19 patients.

Background: The global scarcity of medical oxygen has proven to be catastrophic during the surges in COVID-19 cases over the past two years, with the heaviest burden felt in low- and middle-income countries. Despite its criticality, data and analyses of oxygen consumption, even for typical clinical cases, are missing. Consequently, planning oxygen needs, particularly with variable surges in COVID-19 cases, has presented a substantial challenge to policymakers and hospital decision-makers. Methods: We performed a sub-analysis of the COVID-19 Critical Care Consortium database assessing the oxygen consumption requirements of COVID-19 patients admitted to intensive care units between February 2020 and October 2021. We calculated descriptive statistics for oxygen flow-rates, stratified by oxygen supplementation method, and developed a multi-state model for estimating the frequency, therapy duration, probability of transition, and number of oxygen therapy modes per patient. Results: Overall, 12 429 patients from 35 countries received oxygen support on at least one day of their hospitalisation. Of the patients with measurable flow rates, 6142 received invasive mechanical ventilation, 838 received high-flow nasal oxygen, and 257 received both modalities. The median flow rate for mechanical ventilation was 3.2 L per minute (interquartile range (IQR) = 2.0-4.9), with a median duration of 12 days (IQR = 6-24), while the median flow rate for high-flow nasal cannula was 40 L per minute (IQR = 15-55), with a median duration of three days (IQR = 2-6). Conclusions: Oxygen consumption among critical COVID-19 patients varies by mode of delivery (invasive ventilation vs high-flow nasal cannula), across patients, and over treatment duration. Therefore, it is essential that health facilities routinely monitor oxygen utilization to better inform oxygen delivery system design and regular supply planning. Registration: ClinicalTrials.gov: CTG2021-01 ACTRN12620000421932.

Retinal vessel diameters in intermediate age-related macular degeneration using en face optical coherence tomography.

CLINICAL RELEVANCE: Clinical assessment of age-related macular degeneration (AMD) relies on biomarkers that do not necessarily reflect the contributions of vascular dysfunction. Validation of clinically accessible methods of measuring retinal vascular integrity could provide a more holistic understanding of AMD-related changes to facilitate appropriate care. BACKGROUND: There is conflicting evidence if retinal vessel calibre is significantly altered in the early stages of AMD. This study examined the outer and inner diameters of first order retinal vessels in intermediate AMD eyes using en face optical coherence tomography (OCT). METHODS: Retinal en face (6 × 6 mm) OCT images were examined in a single eye of participants with intermediate AMD (n = 46) versus normal macula (n = 43) for arterioles (all identifiable) and venules (40/46 and 39/43 identifiable). All participants were aged ≥50 years without diabetes mellitus, hypertension, or other systemic vascular disease. RESULTS: Intra- and inter-grader agreement was good-to-excellent for all en face OCT measurements of arteriole and venule diameters (intraclass correlation coefficient = 0.87 to 0.99). Arteriolar outer diameters (82.3 ± 19.8 µm vs 73.8 ± 16.1 µm; p < 0.05) and inner diameters (35.1 ± 8.4 µm vs 31.5 ± 8.1 µm; p < 0.05) were significantly greater in AMD eyes compared to normal eyes. Venular inner diameter was significantly greater (43.1 ± 9.5 µm vs 39.2 ± 10.1 µm; p < 0.05), but outer diameter remained unchanged (p = 0.17) in AMD eyes compared to normal eyes. CONCLUSION: Arteriolar dilation and altered venular inner diameter were observed in intermediate AMD eyes. These results support further investigation of vascular contributions to AMD in the early stages of disease, possibly using the en face OCT imaging modality.

RPE Curvature Can Screen for Early and Intermediate AMD.

Purpose: Diagnosing AMD early optimizes clinical management. However, current diagnostic accuracy is limited by the subjectivity of qualitative diagnostic measures used in clinical practice. This study tests if RPE curvature could be an accurate, quantitative measure for AMD diagnosis. Methods: Consecutive patients without AMD or normal aging changes (n = 111), with normal aging changes (n = 107), early AMD (n = 102) and intermediate AMD (n = 114) were recruited. RPE curvature was calculated based on the sinuosity method of measuring river curvature in environmental science. RPE and Bruch's membrane were manually segmented from optical coherence tomography B-scans and then their lengths automatically extracted using customized MATLAB code. RPE sinuosity was calculated as a ratio of RPE to Bruch's membrane length. Diagnostic accuracy was determined from area under the receiver operator characteristic curve (aROC). Results: RPE sinuosity of foveal B-scans could distinguish any eyes with AMD (early or intermediate) from those without AMD (non-AMD or eyes with normal aging changes) with acceptable diagnostic accuracy (aROC = 0.775). Similarly, RPE sinuosity could identify intermediate AMD from all other groups (aROC = 0.871) and distinguish between early and intermediate AMD (aROC = 0.737). RPE sinuosity was significantly associated with known AMD lesions: reticular pseudodrusen (P < 0.0001) and drusen volume (P < 0.0001), but not physiological variables such as age, sex, and ethnicity. Conclusions: RPE sinuosity is a simple, robust, quantitative biomarker that is amenable to automation and could enhance screening of AMD.

Spatial Analysis Reveals Vascular Changes in Retinal and Choroidal Vessel Perfusion in Intermediate AMD With Reticular Pseudodrusen.

Purpose: To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD) using refined spatial analyses. Methods: This was a retrospective cross-sectional study of 120 individuals with 30 iAMDRPD, 60 iAMDno_RPD, and 30 normal eyes, propensity-score matched by age, sex, and presence of cardiovascular-related disease. VP of the superficial and deep retinal and choriocapillaris vascular slabs was assessed from 6 × 6-mm optical coherence tomography angiography (OCTA) scans divided into 126 × 126 grids, with adjustment for various person- and eye-level factors. Grid-wise VP differences (%) among the groups were spatially assessed according to analyses based on the Early Treatment for Diabetic Retinopathy Study (ETDRS), eccentricity (µm), and degree (°). Results: VP was significantly decreased between iAMDRPD and iAMDno_RPD, across all vascular slabs in various ETDRS sectors (up to -2.16%; 95% confidence interval, -2.99 to -1.34; P < 0.05). Eccentricity analyses revealed more complex patterns: a bisegmented relationship where VP in iAMDRPD eyes decreased linearly toward 1000 µm then returned toward similar values as iAMDno_RPD, plateauing around 2000 µm in the superficial and 3000 µm in the deep retina (R2 = 0.57-0.9; P < 0.001). Degree-based analysis further showed that the greatest VP differences in iAMDRPD eyes were commonly located superiorly and nasally across all vascular slabs (P < 0.05). Conclusions: RPD appears to compound the vascular impact of iAMD, displaying complex spatial patterns beyond the ETDRS sectors. This highlights the importance of considering spatial delineations for future work regarding the role of RPD and vascular dysfunction.

Consistently Exploring Nurse Staffing and Neurocritical Care Unit Turnover.

ABSTRACT: BACKGROUND: Staffing models within nursing units have long been a hot topic of discussion. The COVID-19 pandemic exacerbated this discussion by straining the national nursing environment and workforce. Before the pandemic, the neuroscience intensive care unit (NSICU) primarily used an acuity-adjusted staffing model and aimed for a nurse-to-patient ratio of 1:1.5. During and after the pandemic, the NSICU was forced to primarily use a centralized staffing model because of the increased turnover in the hospital at large and a rise in patient census. METHODS : Unit census data in an NSICU were tracked before, during, and after the pandemic alongside utilization of a centralized staffing model in the hospital at large. RESULTS : During this time, the NSICU saw a statistically significant increase in average nurse-to-patient ratio and incidences of both floating and tripled assignments. The NSICU simultaneously saw a 180% increase in nursing turnover. CONCLUSION : Although we cannot prove that a centralized staffing model is directly responsible for higher nursing turnover, its utilization led to greater incidence of poor staffing-reflected in deviation from the nurse-to-patient ratio goal of the unit. Nurse staffing concerns play a large role in nurse satisfaction in the workforce: staffing shortages have been described both as a precursor to and as a consequence of increased nursing turnover.

An appraisal of pharmacotherapy-pertinent literature published in 2021 and 2022 for clinicians caring for patients with thermal or inhalation injury.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A MeSH-based, filtered search returned 2,336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.

Evaluating the clinical relevance and reliability of outer retinal band length on optical coherence tomography in retinal disease: a cross-sectional study.

OBJECTIVES: Hyper-reflective outer retinal band (HORB) disruptions are reported across a range of retinal disease, yet a reliable, easily implemented assessment method and thorough evaluation of their association to retinal disease is lacking. The purpose of the study was to assess the reliability of using magnitude estimation to evaluate HORB length and determine its association to visual acuity and retinal disease. DESIGN: Cross-sectional, retrospective study. SETTING: Patients attending a secondary eye care clinic in Sydney, Australia. PARTICIPANTS: 2039 unique consecutive patients were screened for inclusion between 2 November and 18 January 2021, and 600 were included in the study population. Patients were included if they were referred from primary care, presented for an initial, comprehensive eye examination during the study period, imaged with optical coherence tomography during their visit and over 18 years of age. PRIMARY OUTCOME: Reliability of HORB length estimations and associations to clinical outcomes. RESULTS: Intragrader (intraclass correlation coefficient, ICCfovea=0.81; ICCworst=0.91) and intergrader (ICCfovea=0.78-0.79; ICCworst=0.75-0.88) agreement of HORB length was good to excellent. HORB length was significantly associated with age (p<0.001, ß=-0.22 to -0.24) and refractive error (p<0.001, ß=0.12-0.16) at all B-scan locations. Visual acuity (p=0.001, ß=-0.13) was associated with the primary outcome for foveal B-scans and eccentricity (p=0.002, ß=-0.13) and device type (p=0.002, ß=0.13) for non-foveal B-scans. Glaucoma was associated with HORB length on univariate analysis (p=0.05-0.06, ß=-0.08); however, multivariate analysis revealed no significant association between HORB length and retinal disease. CONCLUSION: HORB length is reliably assessed using magnitude estimation and may be useful as a surrogate biomarker of visual acuity. Several factors affect HORB length estimations, which may contribute to the lack of association to retinal disease and highlights the need for covariable adjustment when examining HORB disruptions.

Development of a rabbit model of Adenosine triphosphate-induced monocular retinal degeneration for optimization of retinal prostheses.

Optimization of retinal prostheses requires preclinical animal models that mimic features of human retinal disease, have appropriate eye sizes to accommodate implantable arrays, and provide options for unilateral degeneration so as to enable a contralateral, within-animal control eye. In absence of a suitable non-human primate model and shortcomings of our previous feline model generated through intravitreal injections of Adenosine Triphosphate (ATP), we aimed in the present study to develop an ATP induced degeneration model in the rabbit. Six normally sighted Dutch rabbits were monocularly blinded with this technique. Subsequent retinal degeneration was assessed with optical coherence tomography, electroretinography, and histological assays. Overall, there was a 42% and 26% reduction in a-wave and oscillatory potential amplitudes in the electroretinograms respectively, along with a global decrease in retinal thickness, with increased variability. Qualitative inspection also revealed that there were variable levels of retinal degeneration and remodeling both within and between treated eyes, mimicking the disease heterogeneity observed in retinitis pigmentosa. These findings confirm that ATP can be utilized to unilaterally induce blinding in rabbits and, potentially present an ideal model for future cortical recording experiments aimed at optimizing vision restoration strategies.Clinical Relevance- A rapid, unilaterally induced model of retinal degeneration in an animal with low binocular overlap and large eyes will allow for clinically valid recordings of downstream cortical activity following retinal stimulation. Such a model would be highly beneficial for the optimization of clinically appropriate vision restoration approaches.

OCT Prognostic Biomarkers for Progression to Late Age-related Macular Degeneration: A Systematic Review and Meta-analysis.

TOPIC: To evaluate which OCT prognostic biomarkers best predict the risk of progression from early/intermediate to late age-related macular degeneration (AMD). CLINICAL RELEVANCE: Among > 100 OCT prognostic biomarkers for AMD, it is unclear which are the most relevant for clinicians and researchers to focus on. This review evaluated which OCT biomarkers confer the greatest magnitude of prediction for progression to late AMD. METHODS: Study protocol was registered on PROSPERO (CRD42023400166). PubMed and Embase were searched from inception to March 2, 2023, and eligible studies assessed following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was any quantified risk of progression from treatment-naive early/intermediate AMD to late AMD, including hazard ratios (HRs), odds ratios (ORs), and standardized mean differences (at baseline, between eyes with versus without progression), subgrouped by each OCT biomarker. Further meta-analyses were subgrouped by progression to geographic atrophy or neovascularization. RESULTS: A total of 114 quantified OCT prognostic biomarkers were identified. With high GRADE certainty of evidence, the greatest magnitudes of prediction to late AMD belonged to: external limiting membrane abnormality (OR, 15.42 [7.63, 31.17]), ellipsoid zone abnormality (OR, 10.8 [4.58, 25.46]), interdigitation zone abnormality (OR, 7.68 [2.57, 23]), concurrent large drusen and reticular pseudodrusen (HR, 6.73 [1.35, 33.65], hyporeflective drusen cores (HR, 2.48 [1.8, 3.4]; OR 1.85 [1.29, 2.66]), intraretinal hyperreflective foci (IHRF; HR, 2.16 [0.92, 5.07]; OR 5.08 [3.26, 7.92]), and large drusen (HR, 2.01 [1.35, 2.99]); OR, 1.98 [1.27, 3.08]). There was greater risk of geographic atrophy for IHRF and hyporeflective drusen cores (P < 0.05), and neovascularization for ellipsoid zone abnormality (P < 0.05). Other OCT biomarkers such as drusenoid pigment epithelium detachment, shallow irregular retinal pigment epithelium elevations, and nascent geographic atrophy exhibited large magnitudes of risk but required further studies for validation. CONCLUSION: This review synthesizes the 6 most relevant OCT prognostic biomarkers for AMD with greater predictive ability than large drusen alone, for clinicians and researchers to focus on. Further study is required to validate other biomarkers with less than high certainty of evidence, and assess how the copresence of biomarkers may affect risks. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A Systematic Review of the Effectiveness of Health Education Programs for Cervical Cancer Prevention in Rural Communities: Implications for Promoting Health Equity.

Rural women face an increased risk of cervical cancer diagnosis in comparison to women living in metropolitan areas. This review synthesized and critically evaluated cervical cancer screening interventions that target women living in rural communities in the USA. EBSCO, JSTOR, Medline, PsychINFO, Psychology and Behavioral Sciences Collection, PubMed, and Cochrane Library were searched using keywords related to cervical cancer screening, rural communities, and prevention interventions. Study eligibility included randomized controlled trials or quasi-experimental designs, a psychosocial or educational intervention targeting cervical cancer prevention, and implementation in a rural setting. Eleven articles met criteria for the systematic review and 6 of those included information sufficient for meta-analysis. Cochrane guidelines, CONSORT-Equity 2017, and PROGRESS-Plus were used to assess included studies. The systematic review encompassed 9720 participants who were involved in a variety of intervention types: social media campaigns, faith-based, and patient navigation with lay health advisors. None of the studies met all criteria for the health equity assessment. The meta-analysis found that women in the intervention groups were more likely to participate in cervical cancer screening than women in control groups (OR: 2.43, 95% CI: 1.49 to 3.97). The type of intervention mattered in increasing cervical cancer screening participation for women living in rural communities. Educational interventions in combination with patient navigation saw the most success in promoting cervical cancer screening. Further, health inequities focus is lacking robust consideration. Our results highlight a continued need to develop multicomponent interventions with a health equity focus to address barriers to screening and prevention.

Microbially mediated fossil concretions and their characterization by the latest methodologies: a review.

The study of well-preserved organic matter (OM) within mineral concretions has provided key insights into depositional and environmental conditions in deep time. Concretions of varied compositions, including carbonate, phosphate, and iron-based minerals, have been found to host exceptionally preserved fossils. Organic geochemical characterization of concretion-encapsulated OM promises valuable new information of fossil preservation, paleoenvironments, and even direct taxonomic information to further illuminate the evolutionary dynamics of our planet and its biota. Full exploitation of this largely untapped geochemical archive, however, requires a sophisticated understanding of the prevalence, formation controls and OM sequestration properties of mineral concretions. Past research has led to the proposal of different models of concretion formation and OM preservation. Nevertheless, the formation mechanisms and controls on OM preservation in concretions remain poorly understood. Here we provide a detailed review of the main types of concretions and formation pathways with a focus on the role of microbes and their metabolic activities. In addition, we provide a comprehensive account of organic geochemical, and complimentary inorganic geochemical, morphological, microbial and paleontological, analytical methods, including recent advancements, relevant to the characterization of concretions and sequestered OM. The application and outcome of several early organic geochemical studies of concretion-impregnated OM are included to demonstrate how this underexploited geo-biological record can provide new insights into the Earth's evolutionary record. This paper also attempts to shed light on the current status of this research and major challenges that lie ahead in the further application of geo-paleo-microbial and organic geochemical research of concretions and their host fossils. Recent efforts to bridge the knowledge and communication gaps in this multidisciplinary research area are also discussed, with particular emphasis on research with significance for interpreting the molecular record in extraordinarily preserved fossils.

Study protocol for virtual leisure investigating the effect of virtual reality-delivered stress reduction, entertainment and distraction on the use of coercion and need-based medication and patient satisfaction at a closed psychiatric intensive care unit - a mixed-methods pilot clinical trial.

INTRODUCTION: The environment at a psychiatric inpatient ward can lead to emotional distress and behavioural deviations in vulnerable individuals potentially resulting in conflicts, increased use of need-based medication and coercive actions, along with low satisfaction with treatment. To accommodate these challenges, recreational and entertaining interventions are recommended. The tested interventions have, however, shown varying effects and demand a high degree of planning and staff involvement while being difficult to adapt to individual needs. Virtual reality (VR) may help overcome these challenges. METHODS AND ANALYSIS: The study is a mixed-methods clinical trial with a target sample of 124 patients hospitalised at a closed psychiatric ward in the capital region of Denmark. Outcomes (eg, coercion, need-based medication and perceived stress) for a 12-month period where all patients are offered VR-based recreational experiences during their hospitalisation will be compared with outcomes for a 12-month period where VR is not offered. Feasibility and acceptability will be explored with qualitative interviews supplemented with non-participant observations and focus groups. The study began on 1 January 2023, and we expect to complete data collection by 31 December 2024. ETHICS AND DISSEMINATION: The study is registered at Danish Data Protection Agency (j.no P-2022-466) and is approved by the Committee on Health Research Ethics of the capital region of Denmark (j.no 22013313). All patients will be required to provide informed consent. Results from this study will be disseminated via peer-reviewed journals and congress/consortium presentations. TRIAL REGISTRATION NUMBER: NCT05654740.

Spatial Cluster Patterns of Retinal Sensitivity Loss in Intermediate Age-Related Macular Degeneration Features.

Purpose: To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD). Methods: One-hundred individuals (53 iAMD, 47 normal) underwent 10-2 mesopic microperimetry testing in one eye. Pointwise sensitivities (dB) were corrected for age, sex, iAMD status, and co-presence of co-localized key iAMD features: drusen load, pigmentary abnormalities, and reticular pseudodrusen (RPD). Clusters (labeled by ranks of magnitude C-2, C-1, C0) were derived from pointwise sensitivities and then assessed by quadrants and eccentricity/rings. Results: Two clusters of decreased sensitivities were evident in iAMD versus normal: C-2, -1.67 dB (95% CI (confidence intervals), -2.36 to -0.98; P < 0.0001); C-1, -0.93 dB (95% CI, -1.5 to -0.36; P < 0.01). One cluster of decreased sensitivity was independently associated each with increased drusen load (13.57 µm increase per -1 dB; P < 0.0001), pigmentary abnormalities (C-1: -2.23 dB; 95% CI, -3.36 to -1.1; P < 0.01), and RPD (C-1: -1.07 dB; 95% CI, -2 to -0.14; P < 0.01). Sensitivity loss in iAMD was biased toward the superior and central macula (P = 0.16 to <0.0001), aligning with structural distributions of features. However, sensitivity loss associated with drusen load also extended to the peripheral macula (P < 0.0001) with paracentral sparing, which was discordant with the central distribution of drusen. Conclusions: Drusen load, pigmentary abnormalities, and RPD are associated with patterns of retinal sensitivity loss commonly demonstrating superior and central bias. Results highlighted that a clinical focus on these three key iAMD features using structural measures alone does not capture the complex, spatial extent of vision-related functional impairment in iAMD. Translational Relevance: Defining the spatial patterns of retinal sensitivity loss in iAMD can facilitate a targeted visual field protocol for iAMD assessment.

Learning from Latent Safety Threats Identified During Simulation to Improve Patient Safety.

BACKGROUND: Latent safety threats (LSTs-characteristics of design, processes, or physical environment in health care compromising patient safety) are commonly revealed during simulation-based training. Methods of collecting, analyzing, and classifying LSTs are underdeveloped and not standardized. Building on a large simulation program in one organization, the authors aimed to collect LSTs systematically and develop a taxonomy to classify them. METHODS: The authors modified the Press Ganey Healthcare Performance Improvement Failure Modes Taxonomy (HPI-FMT), a standardized framework for safety event classification in health care, and used three categories: System, Individual, and Medications. The subcategories were revised to reflect simulation LST content and promote consistent data entry into a spreadsheet. Data visualization software was used to analyze LST data and generate dashboards, graphs, and executive summaries to share across the system that depicted data for individual hospitals and outpatient areas and allowed grouping, comparisons, and trending. RESULTS: Over a year, the researchers identified 1,318 LSTs in 232 simulations across the organization-a rate of 5.7 LSTs/simulation. The top three LST subcategories were Environment/supplies/equipment (System category); Process/structure (System category); and Knowledge or unformed skill/habit (Individual category). Other important LSTs were Missing/malfunctioning supplies/equipment; Unclear or ineffective process or no process; and Unfamiliarity with supplies/equipment. When a repetitive pattern of LSTs was observed (for example, improper dantrolene use during malignant hyperthermia simulations), targeted process improvement or training was implemented. CONCLUSION: The authors developed, implemented, and refined a systematic method of collecting, analyzing, displaying LSTs, and recommending targeted process improvements or training when LST trends were noted.

Signalling between the sexes during pollen tube reception.

Plant reproduction is a complex, highly-coordinated process in which a single, male germ cell grows through the maternal reproductive tissues to reach and fertilise the egg cell. Focussing on Arabidopsis thaliana, we review signalling between male and female partners which is important throughout the pollen tube journey, especially during pollen tube reception at the ovule. Numerous receptor kinases and their coreceptors are implicated in signal perception in both the pollen tube and synergid cells at the ovule entrance, and several specific peptide and carbohydrate ligands for these receptors have recently been identified. Clarifying the interplay between these signals and the downstream responses they instigate presents a challenge for future research and may help to illuminate broader principles of plant cell-cell communication.