Neurovascular coupling in the visual cortex

This research aimed to improve understanding of neurovascular coupling, focussing on the V1 area of the visual cortex. Neurovascular coupling is the process by which the energetic requirements of the brain are met by increases in local blood flow to areas of neuronal activity. The precise mechanisms underlying this are yet to be fully elucidated, however, it is likely to involve multiple cell types (including vascular mural cells, interneurons and astrocytes) through multiple possible pathways. Increasing our understanding of this process is of great importance: functional magnetic resonance imaging (fMRI) is a widely used technique that measures local changes in blood flow in order to extrapolate findings to neuronal activity. However, little is known about the relationship between increases in blood flow and the activity of specific neuronal subtypes underlying it. This therefore limits the conclusions that can be drawn and the level of detail in which it can be understood. Furthermore, a more nuanced understanding of the characteristics of the vasculature and how this relates to its functionality is required in order to deepen understanding of the role different vessel types and their accompanying vascular mural cells might play in neurovascular coupling, and more specifically how neuronal activity might differentially affect various parts of the vasculature with differing properties. Neurovascular coupling was probed using an in vivo mouse model with a chronic awake head fixed preparation, which allowed sporadic bouts of volitional locomotion. Through this method we were able to observe varying changes in vascular diameter and neuronal intracellular calcium with manipulation of a visual stimulus and varying patterns of locomotion. The function of the vasculature was also characterised in terms of vessel branching order, diameter and inter-soma distance of vascular mural cells; and using ex vivo immunolabellling, markers of vascular function were also characterised in relation to these characteristics

Natural emotion vocabularies and borderline personality disorder

Background Emotion dysregulation is a characteristic central to borderline personality disorder (BPD). Valuably, verbal behaviour can provide a unique perspective for studying emotion dysregulation in BPD, with recent research suggesting that the varieties of emotion words one actively uses (i.e., active emotion vocabularies [EVs]) reflect habitual experience and potential dysregulation therein. Accordingly, the present research examined associations between BPD and active EVs across two studies. Methods Study 1 (N = 530) comprised a large non-clinical sample recruited from online forums, whereby BPD traits were measured via self-report. Study 2 (N = 64 couples) consisted of mixed-gender romantic couples in which the woman had a BPD diagnosis, as well as a control group of couples. In both studies, participants’ verbal behaviours were analysed to calculate their active EVs. Results Results from both studies revealed BPD to be associated with larger negative EV (i.e., using a broad variation of unique negative emotion words), which remained robust when controlling for general vocabulary size and negative affect word frequency in Study 2. The association between BPD and negative EV was insensitive to context. Limitations Limitations of this research include: 1) the absence of a clinical control group; 2) typical constraints surrounding word-counting approaches; and 3) the cross-sectional design (causality cannot be inferred). Conclusions Our findings contribute to BPD theory as well as the broader language and emotion literature. Importantly, these findings provide new insight into how individuals manifesting BPD attend to and represent their emotional experiences, which could be used to inform clinical practice

Core outcome measures for palliative and end-of-life research after severe stroke: mixed-method Delphi study

Background and Purpose: Stroke is the second commonest cause of death worldwide and a leading cause of severe disability, yet there are no published trials of palliative care in stroke. To design and evaluate palliative care interventions for people with stroke, researchers need to know what measurable outcomes matter most to patients and families, stroke professionals, and other service providers. Methods: A multidisciplinary steering group of professionals and laypeople managed the study. We synthesized recommendations from respected United Kingdom and international consensus documents to generate a list of outcome domains and then performed a rapid scoping literature review to identify potential outcome measures for use in future trials of palliative care after stroke. We then completed a 3-round, online Delphi survey of professionals, and service users to build consensus about outcome domains and outcome measures. Finally, we held a stakeholder workshop to review and finalize this consensus. Results: We generated a list of 36 different outcome domains from 4 key policy documents. The rapid scoping review identified 43 potential outcome measures that were used to create a shortlist of 16 measures. The 36 outcome domains and 16 measures were presented to a Delphi panel of diverse healthcare professionals and lay service users. Of 48 panelists invited to take part, 28 completed all 3 rounds. Shared decision-making and quality of life were selected as the most important outcome domains for future trials of palliative care in stroke. Additional comments highlighted the need for outcomes to be feasible, measurable, and relevant beyond the initial, acute phase of stroke. The stakeholder workshop endorsed these results. Conclusions: Future trials of palliative care after stroke should include pragmatic outcome measures, applicable to the evolving patient and family experiences after stroke and be inclusive of shared decision-making and quality of life

The reliability and heritability of cortical folds and their genetic correlations across hemispheres

Cortical folds help drive the parcellation of the human cortex into functionally specific regions. Variations in the length, depth, width, and surface area of these sulcal landmarks have been associated with disease, and may be genetically mediated. Before estimating the heritability of sulcal variation, the extent to which these metrics can be reliably extracted from in-vivo MRI must be established. Using four independent test-retest datasets, we found high reliability across the brain (intraclass correlation interquartile range: 0.65–0.85). Heritability estimates were derived for three family-based cohorts using variance components analysis and pooled (total N \u3e 3000); the overall sulcal heritability pattern was correlated to that derived for a large population cohort (N \u3e 9000) calculated using genomic complex trait analysis. Overall, sulcal width was the most heritable metric, and earlier forming sulci showed higher heritability. The inter-hemispheric genetic correlations were high, yet select sulci showed incomplete pleiotropy, suggesting hemisphere-specific genetic influences

Nitrogen Fertilizer Guide for First-Year Small Grains Following Alfalfa

Nitrogen (N) fertilizer is one of the most expensive crop inputs. It is an essential nutrient for most crops and often increases yield more than any other nutrient. Small grains are no exception. Alfalfa is the dominant crop in Utah in terms of area and gross sales, and as a nitrogen-fixing legume, it does not require nitrogen fertilizer. When terminated, alfalfa usually leaves a lot of nitrogen in the soil for subsequent crops. The amount of nitrogen that it supplies to following crops has been termed the “alfalfa N credit.” In many cases, this credit can be up to 300 lbs. N/acre for the two crops following alfalfa. This fact sheet addresses the nitrogen fertilizer needs of small grains grown for forage and for grain and corresponding economics

Real world performance of privacy preserving record linkage

Introduction Privacy preserving record linkage (PPRL) using encoded or hashed data has potential to enable large-scale record linkage of previously inaccessible data. With limited real-world evaluation and implementation of PPRL at scale it is challenging for linkage practitioners to judiciously balance data protection with the accuracy and usability of linked datasets. Objectives and Approach We evaluated the performance of PPRL techniques using Bloom filters for linkage of data across primary and secondary care settings. This technique limits the need to disclose personal information for linkage activities. Primary care data included 272,202 records from 16 general practices in NSW. This was linked to 42.8 million records from a 7 year series of emergency presentations, hospitalisations and death registrations. For the purpose of evaluation, personal information was encoded within the data linkage centre. The quality of PPRL linkage was assessed against the true match status based on a gold standard probabilistic linkage using full personal identifiers. Results Compared to the gold standard probabilistic linkage using full personal identifiers, the PPRL techniques produced quality metrics of precision, recall and F measure in excess of 0.90. When configured to leverage pre-existing links between emergency department, hospital and mortality data, quality metrics around 0.98-0.99 were achieved. Lower rates of linkage quality were associated with missing demographic information and some residual variation in linkage quality across practices was observed. Conclusion/Implications PPRL using Bloom filters is a promising technique for achieving high quality linkage across primary and secondary care in Australia. Further evaluation will assess scalability and quality in Australia but international collaborations are encouraged to more rapidly develop the evidence base and tactical approaches to support real world implementations

Canadian trends in the social determinants of health inequalities, a census-mortality linkage approach

Introduction Mortality inequalities by income and education levels have historically been estimated using an area-based approach in Canada. Although useful in measuring socioeconomic inequalities overtime, this method underestimates the level of inequality and only allows the examination of a single dimension at a time. Objectives and Approach To create a series of census linked datasets that allowed for the examination of health inequalities across different socioeconomic dimensions. Specifically, five census cycles (beginning with the 1991 Census) were probabilistically and deterministically linked to different health outcomes (mortality, cancer, hospitalization) to create the Canadian Census Health and Environment Cohort (CanCHEC). Each dataset was created using a similar methodological approach which allowed for the measurement of these health inequalities over time. Mortality inequalities by both income and education level (including multidimensional) for all causes and cause-specific groups were examined. Results Five census linked datasets were constructed that followed mortality for a period of up to 20 years. The 1991 CanCHEC includes 2.6 million adults, the 1996 and 2001 CanCHECs include 3.5 million adults respectively, and the 2006 and 2011 CanCHECs include 5.9 and 6.5 million people respectively. Findings revealed a stair-stepped gradient in all-cause and cause-specific mortality by educational attainment and income quintile across each time period. The lowest mortality rates were among the university educated and richest income quintile and highest mortality rates among those with less than high school graduation and the poorest income quintile. The gradient differed by cause of death groupings. Over the 25-year time period, the mortality gradient trend varied by socioeconomic dimension and cause of death. Conclusion/Implications These data show clear mortality inequalities by socioeconomic position across the different time periods. These linked datasets can help advance knowledge in understanding health inequalities in Canada as well as provide a tool for on-going surveillance of health inequalities by different socioeconomic dimensions

Gradual not sudden change: multiple sites of functional transition across the microvascular bed

In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain’s microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localized functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specializations irrespective of their position within the network. Together this work emphasizes the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease

A brief conversation analytic communication intervention can change history-taking in the seizure clinic

Question design during history-taking has clear implications for patients' ability to share their concerns in general and their seizure experiences in particular. Studies have shown that unusually open questions at the start of the consultation enable patients to display interactional and linguistic markers which may help with the otherwise challenging differentiation of epileptic from nonepileptic seizures (NES). In this study, we compared the problem presentation approach taken by trainee neurologists in outpatient encounters with new patients before and after a one-day conversation analytic training intervention in which doctors were taught to adopt an open format of question design and recognize diagnostically relevant linguistic features. We audio/video-recorded clinical encounters between ten doctors, their patients, and accompanying persons; transcribed the interactions; and carried out quantitative and qualitative analyses. We studied 39 encounters before and 55 after the intervention. Following the intervention, doctors were significantly more likely to use nondirective approaches to soliciting patient accounts of their presenting complaints that invited the patient to describe their problems from their own point of view and gave them better opportunity to determine the initial agenda of the encounter. The time to first interruption by the doctor increased (from 52 to 116 s, p<.001). While patients were given more time to describe their seizure experiences, the overall appointment length did not increase significantly (19 vs 21 min, n.s.). These changes gave patients more conversational space to express their concerns and, potentially, to demonstrate the interactional and linguistic features previously found to help differentiate between epilepsy and NES, without impacting the length of the consultations