Gender, Race/Ethnicity, and Patient-Therapist Matching on Gender and Race/Ethnicity: Predictors/Moderators of the Effectiveness of Trust/Respect Feedback.

A plethora of studies has exhibited the effectiveness of using measurement-based care feedback systems within mental health services to improve treatment outcomes; however, patient gender/race and patient-therapist matching on gender and race remain relatively unexplored as predictors/moderators in feedback studies. We conducted predictor/moderator analyses focusing on the relation of gender, race/ethnicity, and patient-therapist gender and race/ethnicity matching on two outcomes: patient self-reported levels of (1) functioning and (2) trust/respect within the therapeutic relationship. We used data from a randomized controlled trial studying the effectiveness of a feedback system comparing patient-reported levels of trust and respect towards their provider (together with symptom feedback) in comparison to symptom only feedback. We found that men improved in functioning more than women when their therapists received trust/respect feedback compared to symptom only feedback (F[1, 902] = 9.79, p = .002, d = 0.21). We also found that dyads matched on race/ethnicity but not gender, and those matched on gender but not race/ethnicity, improved in functioning over time more than dyads mismatched on both gender and race/ethnicity and those matched on both gender and race/ethnicity (F[1, 897] = 8.63, p = .0034, d = 0.20). On trust/respect outcomes, we found a gender difference over time (F[1, 759] = 6.61, p = .01, d = 0.19), a gender matching difference by feedback condition interaction (F[1, 757] = 5.25, p = .02, d = 0.17), and a racial/ethnic matching difference on trust/respect scores over time (F[1, 785] = 3.89, p = .049, d = 0.14). Male patients showed an initial decrease followed by a steady increase in trust/respect over time while female patients showed an initial increase followed by a steady decrease. Gender-matched therapeutic dyads showed higher levels of trust/respect compared to mismatched dyads when therapists received symptom only feedback, but this difference was not apparent when trust/respect feedback was provided. Dyads mismatched on race/ethnicity improved steadily in trust/respect over time, but matched dyads decreased in trust/respect after an initial increase. Future research should focus on the use of feedback systems to enhance outcomes for patients with specific gender and racial/ethnic identities.

Refined high-content imaging-based phenotypic drug screening in zebrafish xenografts.

Zebrafish xenotransplantation models are increasingly applied for phenotypic drug screening to identify small compounds for precision oncology. Larval zebrafish xenografts offer the opportunity to perform drug screens at high-throughput in a complex in vivo environment. However, the full potential of the larval zebrafish xenograft model has not yet been realized and several steps of the drug screening workflow still await automation to increase throughput. Here, we present a robust workflow for drug screening in zebrafish xenografts using high-content imaging. We established embedding methods for high-content imaging of xenografts in 96-well format over consecutive days. In addition, we provide strategies for automated imaging and analysis of zebrafish xenografts including automated tumor cell detection and tumor size analysis over time. We also compared commonly used injection sites and cell labeling dyes and show specific site requirements for tumor cells from different entities. We demonstrate that our setup allows us to investigate proliferation and response to small compounds in several zebrafish xenografts ranging from pediatric sarcomas and neuroblastoma to glioblastoma and leukemia. This fast and cost-efficient assay enables the quantification of anti-tumor efficacy of small compounds in large cohorts of a vertebrate model system in vivo. Our assay may aid in prioritizing compounds or compound combinations for further preclinical and clinical investigations.

Implementing human factors in anaesthesia: guidance for clinicians, departments and hospitals: Guidelines from the Difficult Airway Society and the Association of Anaesthetists: Guidelines from the Difficult Airway Society and the Association of Anaesthetists.

Human factors is an evidence-based scientific discipline used in safety critical industries to improve safety and worker well-being. The implementation of human factors strategies in anaesthesia has the potential to reduce the reliance on exceptional personal and team performance to provide safe and high-quality patient care. To encourage the adoption of human factors science in anaesthesia, the Difficult Airway Society and the Association of Anaesthetists established a Working Party, including anaesthetists and operating theatre team members with human factors expertise and/or interest, plus a human factors scientist, an industrial psychologist and an experimental psychologist/implementation scientist. A three-stage Delphi process was used to formulate a set of 12 recommendations: these are described using a 'hierarchy of controls' model and classified into design, barriers, mitigations and education and training strategies. Although most anaesthetic knowledge of human factors concerns non-technical skills, such as teamwork and communication, human factors is a broad-based scientific discipline with many other additional aspects that are just as important. Indeed, the human factors strategies most likely to have the greatest impact are those related to the design of safe working environments, equipment and systems. While our recommendations are primarily provided for anaesthetists and the teams they work with, there are likely to be lessons for others working in healthcare beyond the speciality of anaesthesia.

Human factors in anaesthesia: a narrative review.

Healthcare relies on high levels of human performance, as described by the 'human as the hero' concept. However, human performance varies and is recognised to fall in high-pressure situations, meaning that it is not a reliable method of ensuring safety. Other safety-critical industries embed human factors principles into all aspects of their organisations to improve safety and reduce reliance on exceptional human performance; there is potential to do the same in anaesthesia. Human factors is a broad-based scientific discipline which aims to make it as easy as possible for workers to do things correctly. The human factors strategies most likely to be effective are those which 'design out' the chance of an error or adverse event occurring. When errors or adverse events do happen, barriers are in place to trap them and reduce the risk of progression to patient and/or worker harm. If errors or adverse events are not trapped by these barriers, mitigations are in place to minimise the consequences. Non-technical skills form an important part of human factors barriers and mitigation strategies and include: situation awareness; decision-making; task management; and team working. Human factors principles are not a substitute for proper investment and appropriate staffing levels. Although applying human factors science has the potential to save money in the long term, its proper implementation may require investment before reward can be reaped. This narrative review describes what is known about human factors in anaesthesia to date.

Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021.

Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe, Africa and North America but are currently absent from South America and Oceania. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John's, Newfoundland and Labrador, Canada. Our phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Our analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.

Nonlesional Sources of Contrast Enhancement on Postgadolinium "Black-Blood" 3D T1-SPACE Images in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: We hypothesized that 3D T1-TSE "black-blood" images may carry an increased risk of contrast-enhancing lesion misdiagnosis in patients with MS because of the misinterpretation of intraparenchymal vein enhancement. Thus, the occurrence of true-positive and false-positive findings was compared between standard MPRAGE and volumetric interpolated brain examination techniques. MATERIALS AND METHODS: Sampling perfection with application-optimized contrasts by using different flip-angle evolution (SPACE) images obtained from 232 patients with MS, clinically isolated syndrome, or radiologically isolated syndrome were compared with standard MPRAGE and volumetric interpolated brain examination images. The intraparenchymal vein contrast-to-noise ratio was estimated at the level of the thalami. Contrast-enhancing lesions were blindly detected by 2 expert readers and 1 beginner reader. True- and false-positives were determined by senior readers' consensus. True-positive and false-positive frequency differences and patient-level diagnosis probability were tested with the McNemar test and OR. The contrast-to-noise ratio and morphology were compared using the Mann-Whitney U and χ2 tests. RESULTS: The intraparenchymal vein contrast-to-noise ratio was higher in SPACE than in MPRAGE and volumetric interpolated brain examination images (P < .001, both). There were 66 true-positives and 74 false-positives overall. SPACE detected more true-positive and false-positive results (P range < .001-.07) but did not increase the patient's true-positive likelihood (OR = 1 1.29, P = .478-1). However, the false-positive likelihood was increased (OR = 3.03-3.55, P = .008-.027). Venous-origin false-positives (n = 59) with contrast-to-noise ratio and morphology features similar to small-sized (≤14 mm3 P = .544) true-positives occurred more frequently in SPACE images (P < .001). CONCLUSIONS: Small intraparenchymal veins may confound the diagnosis of enhancing lesions on postgadolinium black-blood SPACE images.

Making remote measurement technology work in multiple sclerosis, epilepsy and depression: survey of healthcare professionals.

BACKGROUND: Epilepsy, multiple sclerosis (MS) and depression are long term, central nervous system disorders which have a significant impact on everyday life. Evaluating symptoms of these conditions is problematic and typically involves repeated visits to a clinic. Remote measurement technology (RMT), consisting of smartphone apps and wearables, may offer a way to improve upon existing methods of managing these conditions. The present study aimed to establish the practical requirements that would enable clinical integration of data from patients' RMT, according to healthcare professionals. METHODS: This paper reports findings from an online survey of 1006 healthcare professionals currently working in the care of people with epilepsy, MS or depression. The survey included questions on types of data considered useful, how often data should be collected, the value of RMT data, preferred methods of accessing the data, benefits and challenges to RMT implementation, impact of RMT data on clinical practice, and requirement for technical support. The survey was presented on the JISC online surveys platform. RESULTS: Among this sample of 1006 healthcare professionals, respondents were positive about the benefits of RMT, with 73.2% indicating their service would be likely or highly likely to benefit from the implementation of RMT in patient care plans. The data from patients' RMT devices should be made available to all nursing and medical team members and could be reviewed between consultations where flagged by the system. However, results suggest it is also likely that RMT data would be reviewed in preparation for and during a consultation with a patient. Time to review information is likely to be one of the greatest barriers to successful implementation of RMT in clinical practice. CONCLUSIONS: While further work would be required to quantify the benefits of RMT in clinical practice, the findings from this survey suggest that a wide array of clinical team members treating epilepsy, MS and depression would find benefit from RMT data in the care of their patients. Findings presented could inform the implementation of RMT and other digital interventions in the clinical management of a range of neurological and mental health conditions.

The impact of data from remote measurement technology on the clinical practice of healthcare professionals in depression, epilepsy and multiple sclerosis: survey.

BACKGROUND: A variety of smartphone apps and wearables are available both to help patients monitor their health and to support health care professionals (HCPs) in providing clinical care. As part of the RADAR-CNS consortium, we have conducted research into the application of wearables and smartphone apps in the care of people with multiple sclerosis, epilepsy, or depression. METHODS: We conducted a large online survey study to explore the experiences of HCPs working with patients who have one or more of these conditions. The survey covered smartphone apps and wearables used by clinicians and their patients, and how data from these technologies impacted on the respondents' clinical practice. The survey was conducted between February 2019 and March 2020 via a web-based platform. Detailed statistical analysis was performed on the answers. RESULTS: Of 1009 survey responses from HCPs, 1006 were included in the analysis after data cleaning. Smartphone apps are used by more than half of responding HCPs and more than three quarters of their patients use smartphone apps or wearable devices for health-related purposes. HCPs widely believe the data that patients collect using these devices impacts their clinical practice. Subgroup analyses show that views on the impact of this data on different aspects of clinical work varies according to whether respondents use apps themselves, and, to a lesser extent, according to their clinical setting and job role. CONCLUSIONS: Use of smartphone apps is widespread among HCPs participating in this large European survey and caring for people with epilepsy, multiple sclerosis and depression. The majority of respondents indicate that they treat patients who use wearables and other devices for health-related purposes and that data from these devices has an impact on clinical practice.

KDM6A mutations promote acute cytoplasmic DNA release, DNA damage response and mitosis defects.

BACKGROUND: KDM6A, encoding a histone demethylase, is one of the top ten mutated epigenetic cancer genes. The effect of mutations on its structure and function are however poorly characterized. METHODS: Database search identified nonsense and missense mutations in the N-terminal TPR motifs and the C-terminal, catalytic JmjC domain, but also in the intrinsically disordered region connecting both these two well-structured domains. KDM6A variants with cancer-derived mutations were generated using site directed mutagenesis and fused to eGFP serving as an all-in-one affinity and fluorescence tag to study demethylase activity by an ELISA-based assay in vitro, apoptosis by FACS, complex assembly by Co-immunoprecipitation and localization by microscopy in urothelial cells and apoptosis by FACS. RESULTS: Independent of the mutation and demethylase activity, all KDM6A variants were detectable in the nucleus. Truncated KDM6A variants displayed changes in complex assemblies affecting (1) known interactions with the COMPASS complex component RBBP5 and (2) KDM6A-DNA associated assemblies with the nuclear protein Nucleophosmin. Some KDM6A variants induced a severe cellular phenotype characterized by multiple acute effects on nuclear integrity, namely, release of nuclear DNA into the cytoplasm, increased level of DNA damage indicators RAD51 and p-γH2A.X, and mitosis defects. These damaging effects were correlated with increased cell death. CONCLUSION: These observations reveal novel effects of pathogenic variants pointing at new specific functions of KDM6A variants. The underlying mechanisms and affected pathways have to be investigated in future research to understand how tumor cells cope with and benefit from KDM6A truncations.

Fire safety and emergency evacuation guidelines for intensive care units and operating theatres: for use in the event of fire, flood, power cut, oxygen supply failure, noxious gas, structural collapse or other critical incidents: Guidelines from the Association of Anaesthetists and the Intensive Care Society.

The need to evacuate an ICU or operating theatre complex during a fire or other emergency is a rare event but one potentially fraught with difficulty: Not only is there a risk that patients may come to harm but also that staff may be injured and unable to work. Designing newly-built or refurbished ICUs and operating theatre suites is an opportunity to incorporate mandatory fire safety features and improve the management and outcomes of such emergencies: These include well-marked manual fire call points and oxygen shut off valves (area valve service units); the ability to isolate individual zones; multiple clear exit routes; small bays or side rooms; preference for ground floor ICU location and interconnecting routes with operating theatres; separate clinical and non-clinical areas. ICUs and operating theatre suites should have a bespoke emergency evacuation plan and route map that is readily available. Staff should receive practical fire and evacuation training in their clinical area of work on induction and annually as part of mandatory training, including 'walk-through practice' or simulation training and location of manual fire call points and fire extinguishers, evacuation routes and location and operation of area valve service units. The staff member in charge of each shift should be able to select and operate fire extinguishers and lead an evacuation. Following an emergency evacuation, a network-wide response should be activated, including retrieval and transport of patients to other ICUs if needed. A full investigation should take place and ongoing support and follow-up of staff provided.

Combining segmental bulk- and single-cell RNA-sequencing to define the chondrocyte gene expression signature in the murine knee joint.

OBJECTIVE: Due to the small size of the murine knee joint, extracting the chondrocyte transcriptome from articular cartilage (AC) is a major technical challenge. In this study, we demonstrate a new pragmatic approach of combining bulk RNA-sequencing (RNA-seq) and single cell (sc)RNA-seq to address this problem. DESIGN: We propose a new cutting strategy for the murine femur which produces three segments with a predictable mixed cell population, where one segment contains AC and growth plate (GP) chondrocytes, another GP chondrocytes, and the last segment only bone and bone marrow. We analysed the bulk RNA-seq of the different segments to find distinct genes between the segments. The segment containing AC chondrocytes was digested and analysed via scRNA-seq. RESULTS: Differential expression analysis using bulk RNA-seq identified 350 candidate chondrocyte gene in the AC segment. Gene set enrichment analysis of these genes revealed biological processes related- and non-related to chondrocytes, including, cartilage development (adj. P-value: 3.45E-17) and endochondral bone growth (adj. P-value 1.22E-4), respectively. ScRNA-seq of the AC segment found a cluster of 131 cells containing mainly chondrocytes. This cluster had 759 differentially expressed genes which enriched for extracellular matrix organisation (adj. P-value 7.76E-40) and other joint development processes. The intersection of the gene sets of bulk- and scRNA-seq contained 75 genes. CONCLUSIONS: Based on our results, we conclude that the combination of the two RNA-seq methods is necessary to precisely delineate the chondrocyte transcriptome and to study the disease phenotypes of chondrocytes in murine OA models in the future.

Dedicated 3D-T2-STIR-ZOOMit Imaging Improves Demyelinating Lesion Detection in the Anterior Visual Pathways of Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Demyelinating lesions in the anterior visual pathways represent an underestimated marker of disease dissemination in patients with MS. We prospectively investigated whether a dedicated high-resolution MR imaging technique, the 3D-T2-STIR-ZOOMit, improves demyelinating lesion detection compared with the current clinical standard sequence, the 2D-T2-STIR. MATERIALS AND METHODS: 3T MR imaging of the anterior visual pathways (optic nerves, chiasm, and tracts) was performed using 3D-T2-STIR-ZOOMit and 2D-T2-STIR, in patients with MS and healthy controls. Two experienced neuroradiologists assessed, independently, demyelinating lesions using both sequences separately. 3D-T2-STIR-ZOOMit scan-rescan reproducibility was tested in 12 patients. The Cohen κ was used for interrater agreement, and the intraclass correlation coefficient for reproducibility. Between-sequence detection differences and the effects of location and previous acute optic neuritis were assessed using a binomial mixed-effects model. RESULTS: Forty-eight patients with MS with (n = 19) or without (n = 29) past optic neuritis and 19 healthy controls were evaluated. Readers' agreement was strong (3D-T2-STIR-ZOOMit: 0.85; 2D-T2-STIR: 0.90). The 3D-T2-STIR-ZOOMit scan-rescan intraclass correlation coefficient was 0.97 (95% CI, 0.96-0.98; P < .001), indicating excellent reproducibility. Overall, 3D-T2-STIR-ZOOMit detected more than twice the demyelinating lesions (n = 89) than 2D-T2-STIR (n = 43) (OR = 2.7; 95% CI, 1.7-4.1; P < .001). In the intracranial anterior visual pathway segments, 33 of the 36 demyelinating lesions (91.7%) detected by 3D-T2-STIR-ZOOMit were not disclosed by 2D-T2-STIR. 3D-T2-STIR-ZOOMit increased detection of demyelinating lesion probability by 1.8-fold in patients with past optic neuritis (OR = 1.8; 95% CI, 1.2-3.1; P = .01) and 5.9-fold in patients without past optic neuritis (OR = 5.9; 95% CI, 2.5-13.8; P < .001). No false-positive demyelinating lesions were detected in healthy controls. CONCLUSIONS: Dedicated 3D-T2-STIR-ZOOMit images improved substantially the detection of MS disease dissemination in the anterior visual pathways, particularly in the intracranial segments and in patients without past optic neuritis.

Severity of Chest Imaging is Correlated with Risk of Acute Neuroimaging Findings among Patients with COVID-19.

BACKGROUND AND PURPOSE: Severe respiratory distress in patients with COVID-19 has been associated with higher rate of neurologic manifestations. Our aim was to investigate whether the severity of chest imaging findings among patients with coronavirus disease 2019 (COVID-19) correlates with the risk of acute neuroimaging findings. MATERIALS AND METHODS: This retrospective study included all patients with COVID-19 who received care at our hospital between March 3, 2020, and May 6, 2020, and underwent chest imaging within 10 days of neuroimaging. Chest radiographs were assessed using a previously validated automated neural network algorithm for COVID-19 (Pulmonary X-ray Severity score). Chest CTs were graded using a Chest CT Severity scoring system based on involvement of each lobe. Associations between chest imaging severity scores and acute neuroimaging findings were assessed using multivariable logistic regression. RESULTS: Twenty-four of 93 patients (26%) included in the study had positive acute neuroimaging findings, including intracranial hemorrhage (n = 7), infarction (n = 7), leukoencephalopathy (n = 6), or a combination of findings (n = 4). The average length of hospitalization, prevalence of intensive care unit admission, and proportion of patients requiring intubation were significantly greater in patients with acute neuroimaging findings than in patients without them (P < .05 for all). Compared with patients without acute neuroimaging findings, patients with acute neuroimaging findings had significantly higher mean Pulmonary X-ray Severity scores (5.0 [SD, 2.9] versus 9.2 [SD, 3.4], P < .001) and mean Chest CT Severity scores (9.0 [SD, 5.1] versus 12.1 [SD, 5.0], P = .041). The pulmonary x-ray severity score was a significant predictor of acute neuroimaging findings in patients with COVID-19. CONCLUSIONS: Patients with COVID-19 and acute neuroimaging findings had more severe findings on chest imaging on both radiographs and CT compared with patients with COVID-19 without acute neuroimaging findings. The severity of findings on chest radiography was a strong predictor of acute neuroimaging findings in patients with COVID-19.

Leukoencephalopathy Associated with Severe COVID-19 Infection: Sequela of Hypoxemia?

There is increasing evidence to suggest that complications of coronavirus disease 2019 (COVID-19) infection are not only limited to the pulmonary system but can also involve the central nervous system. Here, we report 6 critically ill patients with COVID-19 infection and neuroimaging findings of leukoencephalopathy. While these findings are nonspecific, we postulate that they may be a delayed response to the profound hypoxemia the patients experienced due to the infection. No abnormal enhancement, hemorrhage, or perfusion abnormalities were noted on MR imaging. In addition, Severe Acute Respiratory Syndrome coronavirus 2 was not detected in the CSF collected from the 2 patients who underwent lumbar puncture. Recognition of COVID-19-related leukoencephalopathy is important for appropriate clinical management, disposition, and prognosis.

Opinions and clinical practices related to diagnosing and managing functional (psychogenic) movement disorders: changes in the last decade.

BACKGROUND AND PURPOSE: There is large variability in the diagnostic approach and clinical management in functional movement disorders (FMD). This study aimed to examine whether opinions and clinical practices related to FMD have changed over the past decade. METHODS: Adapted from a 2008 version, we repeated the survey to members of the International Parkinson and Movement Disorder Society (MDS). RESULTS: In all, 864/7689 responses (denominator includes non-neurologists) were received from 92 countries. Respondents were more often male (55%), younger than 45 (65%) and from academic practices (85%). Although the likelihood of ordering neurological investigations prior to delivering a diagnosis of FMD was nearly as high as in 2008 (47% vs. 51%), the percentage of respondents communicating the diagnosis without requesting additional tests increased (27% vs. 19%; P = 0.003), with most envisioning their role as providing a diagnosis and coordinating management (57% vs. 40%; P < 0.001). Compared to patients with other disorders, 64% of respondents were more concerned about missing a diagnosis of another neurological disorder. Avoiding iatrogenic harm (58%) and educating patients about the diagnosis (53%) were again rated as the most effective therapeutic options. Frequent treatment barriers included lack of physician knowledge and training (32%), lack of treatment guidelines (39%), limited availability of referral services (48%) and cultural beliefs about psychological illnesses (50%). The preferred term for communication favored 'functional' over 'psychogenic' (P < 0.001). CONCLUSIONS: Attitudes and management of FMDs have changed over the past decade. Important gaps remain in access to treatment and in the education of neurologists about the inclusionary approach to FMD diagnosis.

Contingent negative variation: a biomarker of abnormal attention in functional movement disorders.

BACKGROUND AND PURPOSE: Contingent negative variation (CNV) is a negative cortical wave that precedes a pre-cued imperative stimulus requiring a quick motor response. It has been related to motor preparation and anticipatory attention. The aim was to ascertain whether the clinical improvement of functional movement disorders after physiotherapy would be associated with faster reaction times and modulation of CNV. METHODS: Motor performance and CNV were analysed during a pre-cued choice reaction time task with varying cue validity. Twenty-one patients with functional movement disorders and 13 healthy controls at baseline were compared. Patients then underwent physiotherapy. At follow-up after physiotherapy, patients were categorized as clinically improved (responders) or not improved (non-responders) and retested. RESULTS: At baseline, patients did not generate CNV, contrary to controls [mean amplitude (µV) at the end of preparation to move: patients -0.47 (95% CI -1.94, 1.00) versus controls -2.59 (95% CI -4.46, -0.72)]. Responders performed faster after physiotherapy [mean natural logarithm (ln) reaction time (RT) (ms): follow-up 6.112 (95% CI 5.923, 6.301) versus baseline 6.206 (95% CI 6.019, 6.394), P = 0.010], contrary to non-responders. Simultaneously, responders showed a recovery of CNV after physiotherapy [follow-up -1.95 (95% CI -3.49, -0.41) versus baseline -0.19 (95% CI -1.73, 1.35), P < 0.001], contrary to non-responders [follow-up -0.32 (95% CI -1.79, 1.14) versus baseline -0.72 (95% CI -2.19, 0.75), P = 0.381]. CONCLUSIONS: Clinical improvement of functional movement disorders after physiotherapy was associated with faster reaction times and normalization of CNV, which was absent at baseline. These findings suggest that CNV may constitute a useful neurophysiological biomarker related to abnormal attention in functional movement disorders.

Gene transfer across species boundaries in bryophytes: evidence from major life cycle stages in Homalothecium lutescens and H. sericeum.

BACKGROUND AND AIMS: The mosses Homalothecium lutescens and H. sericeum are genetically, morphologically and ecologically differentiated; mixed populations sometimes occur. In sympatric populations, intermediate character states among gametophytes and sporophytes have been observed, suggesting hybridization and introgression in such populations. METHODS: We determined genotypes using bi-allelic co-dominant single nucleotide polymorphism (SNP) markers, specific to either H. lutescens or H. sericeum, to estimate the degree of genetic mixing in 449 moss samples collected from seven sympatric and five allopatric populations on the island of Öland, south Sweden. The samples represented three generations: haploid maternal gametophytes; diploid sporophytes; and haploid sporelings. KEY RESULTS: Admixture analyses of SNP genotypes identified a majority as pure H. lutescens or H. sericeum, but 76 samples were identified as mildly admixed (17 %) and 17 samples (3.8 %) as strongly admixed. Admixed samples were represented in all three generations in several populations. Hybridization and introgression were bidirectional. CONCLUSIONS: Our results demonstrate that admixed genomes are transferred between the generations, so that the populations behave as true hybrid zones. Earlier studies of sympatric bryophyte populations with admixed individuals have not been able to show that admixed alleles are transferred beyond the first generation. The presence of true hybrid zones has strong evolutionary implications because genetic material transferred across species boundaries can be directly exposed to selection in the long-lived haploid generation of the bryophyte life cycle, and contribute to local adaptation, long-term survival and speciation.

Brain Tumor-Enhancement Visualization and Morphometric Assessment: A Comparison of MPRAGE, SPACE, and VIBE MRI Techniques.

BACKGROUND AND PURPOSE: Postgadolinium MR imaging is crucial for brain tumor diagnosis and morphometric assessment. We compared brain tumor enhancement visualization and the "target" object morphometry obtained with the most commonly used 3D MR imaging technique, MPRAGE, with 2 other routinely available techniques: sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) and volumetric interpolated brain examination (VIBE). MATERIALS AND METHODS: Fifty-four contrast-enhancing tumors (38 gliomas and 16 metastases) were assessed using MPRAGE, VIBE, and SPACE techniques randomly acquired after gadolinium-based contrast agent administration on a 3T scanner. Enhancement conspicuity was assessed quantitatively by calculating the contrast rate and contrast-to-noise ratio, and qualitatively, by consensus visual comparative ratings. The total enhancing tumor volume and between-sequence discrepancy in the margin delineation were assessed on the corresponding 3D target objects contoured with a computer-assisted software for neuronavigation. The Wilcoxon signed rank and Pearson χ2 nonparametric tests were used to investigate between-sequence discrepancies in the contrast rate, contrast-to-noise ratio, visual conspicuity ratings, tumor volume, and margin delineation estimates. Differences were also tested for 1D (Response Evaluation Criteria in Solid Tumors) and 2D (Response Assessment in Neuro-Oncology) measurements. RESULTS: Compared with MPRAGE, both SPACE and VIBE obtained higher contrast rate, contrast-to-noise ratio, and visual conspicuity ratings in both gliomas and metastases (P range, <.001-.001). The between-sequence 3D target object margin discrepancy ranged between 3% and 19.9% of lesion tumor volume. Larger tumor volumes, 1D and 2D measurements were obtained with SPACE (P range, <.01-.007). CONCLUSIONS: Superior conspicuity for brain tumor enhancement can be achieved using SPACE and VIBE techniques, compared with MPRAGE. Discrepancies were also detected when assessing target object size and morphology, with SPACE providing more accurate estimates.