Academic literature on the topic 'Griese, Brian'

The aircraft referred to in the title are the Airbus Industrie A 310, the Boeing 767 and the Boeing 757. The paper has been written in conjunction with representatives from British Caledonian Airways, Britannia Airways and British Airways, airlines which are currently operating these aircraft. I am indebted to the following for their contributions: Captain Stuart Grieve (Chief Pilot, Britannia Airways), Captain Chris Norman (Britannia Airways), Captain Brian Myers, (Chief Training Captain A 310, British Caledonian Airways), Bill Grice (Chief Development Engineer Avionics, British Airways), Captain Rod Fulton (Flight Training Manager 757, British Airways) and Captain Paul Woodburn (Flight Manager Technical 757, British Airways).

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor-α), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

Aim. To assess laboratory markers of hemodynamic status in patients with moderate to severe COVID-19.Materials and Methods. Here we examined 15 patients with moderate COVID-19 and 16 critically ill COVID-19 patients. The control group consisted of 20 healthy volunteers. The levels of endothelin-1, brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by enzyme-linked immunosorbent assay. The amounts of nitrites (NO2) and nitrates (NO3) were measured by a Griess test (an enzymatic conversion of nitrates to nitrites) with a following colorimetric analysis.Results. Measurements of endothelin-1, nitrites, and nitrates showed high variability. The levels of NT-proBNP were reduced by 65% and 50% in patients with moderate and severe COVID-19, respectively (p < 0.05). In contrast, the levels of BNP were elevated by 472% and 548% in these patient categories (p < 0.05). These results indicated increased left ventricular load and suggested a heart failure.Conclusion. Progressive increase of BNP and concurrent reduction of NT-proBNP indicate affected hemodynamics in patients with moderate and severe COVID-19.

The aim of this study is to identify the effects of KDML105 bran extract on gene expression involving the hair cycle in HFDPCs and investigate its bioactive constituents, antioxidant, and anti-inflammatory activities. The content of tocopherols, γ-oryzanol, phytic acid, and phenolic compounds was quantified by liquid chromatography. Free fatty acids were determined using gas chromatography. Antioxidant capacities were estimated by DPPH, ABTS, and metal chelating assay. The nitric oxide (NO) production was determined by Griess reaction. Gene expression was measured by semi-quantitative RT-PCR. The major compounds in the extract were α- and γ-tocopherol, phytic acid, γ-oryzanol, chlorogenic acid, o-coumaric acid, palmitic acid, oleic acid, and linoleic acid, giving its antioxidant capacities. The nitrite level in lipopolysaccharide-induced macrophages (2.76 ± 0.13 μM) was significantly mitigated by the extract (0.81 ± 0.11 μM). Additionally, SRD5A2 and TGFB1 expressions in HFDPCs were downregulated, whereas CTNNB1 and VEGF genes were upregulated after treatment with the extract. KDML105 extract ameliorated oxidative stress and NO production. According to the gene expression study, KDML105 bran extract may be involved in the induction and maintenance of the anagen phase and angiogenesis in the hair growth pathway. Therefore, KDML105 bran extract might be a promising source of anti-hair loss substances.

We investigated the effects of 7-nitroindazole (7-NI), a selective neuronal nitric oxide synthase inhibitor in vivo, on nitrite concentration after kainic acid injection unilaterally into the CA3 region of the rat hippocampus. The accumulation of nitrite, the stable metabolite of NO, was measured by the Griess reaction at different times in hippocampus, forebrain cortex, striatum, and cerebellum homogenates. 7-nitroindazole can effectively inhibit NO synthesis in rat brain after kainate-induced neurotoxicity and suppressed nitrite accumulation. The present results suggest that neuronal NO synthase inhibitors may be useful in the treatment of neurological diseases in which excitotoxic mechanisms play a role. <br><br><font color="red"><b> This article has been retracted. Link to the retraction <u><a href="http://dx.doi.org/10.2298/ABS160412036E">10.2298/ABS160412036E</a><u></b></font>

Nitric oxide is hypothesised to play a role in the immunopathogenesis of multiple sclerosis. Raised cerebrospinal fluid and serum levels of the nitric oxide metabolites nitrate and nitrite have been described in patients with multiple sclerosis. Cerebrospinal fluid and serum nitrate and nitrite were measured in patients with multiple sclerosis, inflammatory and non-inflammatory neurological diseases, and correlated with the albumin quotient, an index of blood-brain-barrier dysfunction. Patients undergoing diagnostic lumbar and vene puncture were prospectively recruited, clinical data were obtained from the hospital records, and the CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. Nitrate and nitrite, were raised in the CSF and serum of patients with multiple sclerosis and other inflammatory neurological diseases compared to patients with non-inflammatory neurological disorders (median nitrate and nitrite: cerebrospinal fluid=10.3 μM vs 15.4 μMvs 6.6 μM, P50.001, and serum=49.0 μM vs 46.4 μM vs 38.8 μM, P=0.02, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient (n=59, r=0.42, P50.001). This study provides further evidence for a role of nitric oxide in the immunopathogenesis of multiple sclerosis and supports a role for nitric oxide as a possible mediator of inflammatory blood-brain-barrier dysfunction.

Stimulation of glutamate receptors induces neuronal nitric oxide (NO) release, which in turn modulates glutamate transmission. The involvement of ionotropic glutamate NMDA and AMPA/kainate receptors in induction of NO production in the rat brain was examined after injection of kainate, a non-NMDA receptor agonist; kainate plus 6-cyano- 7-nitroquinoxaline-2,3-dione (CNQX), a selective AMPA/kainate receptor antagonist; or kainate plus 2-amino-5-phosphonopentanoic acid (APV), a selective NMDA receptor antagonist. Competitive glutamate receptor antagonists were injected with kainate unilaterally into the CA3 region of the rat hippocampus. The accumulation of nitrite, the stable metabolite of NO, was measured by the Griess reaction at different times (5 min, 15 min, 2 h, 48 h, and 7 days) in hippocampus, forebrain cortex, striatum, and cerebellum homogenates. The used glutamate antagonists APV and CNQX both provided sufficient neuroprotection in the sense of reducing nitrite concentrations, but with different mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in nitric oxide production. <br><br><font color="red"><b> This article has been retracted. Link to the retraction <u><a href="http://dx.doi.org/10.2298/ABS150319031E">10.2298/ABS150319031E</a><u></b></font>

Introduction: To study the effects of glufimet, a new derivative of glutamic acid, and phenibut, a derivative of γ-aminobutyric acid (GABA), on cardiac and cerebral mitochondria and endothelial functions in animals following exposure to stress and inducible nitric oxide synthase (iNOS) inhibition. Methods: Rats suspended by their dorsal cervical skin fold for 24 hours served as the immobilization and pain stress model. Arterial blood pressure was determined using a non-invasive blood pressure monitor. Mitochondrial fraction of heart and brain homogenates were isolated by differential centrifugation and analysed for mitochondrial respiration intensity, lipid peroxidation (LPO) and antioxidant enzyme activity using polarographic method. The concentrations of nitric oxide (NO) terminal metabolites were measured using Griess reagent. Hemostasis indices were evaluated. Platelet aggregation was estimated using modified version of the Born method described by Gabbasov et al., 1989. Results: The present study demonstrated that stress leads to an elevated concentration of NO terminal metabolites and LPO products, decreased activity of antioxidant enzymes, reduced mitochondrial respiratory function, and endothelial dysfunction. Inhibition of iNOS by aminoguanidine had a protective effect. Phenibut and glufimet inhibited a rise in stress-induced nitric oxide production. This resulted in enhanced coupling of substrate peroxidation and ATP synthesis. The reduced LPO processes caused by glufimet and phenibut normalized the endothelial function which was proved by the absence of average daily blood pressure (BP) elevation episodes and a significant increase in platelet aggregation level. Conclusion: Glufimet and phenibut restrict the harmful effects of stress on the heart and brain possibly by modulating iNOS activity.

The study was to investigate the effects of ligustrazine on rats with cerebral ischemia–reperfusion (I/R) injury and to explore the potential mechanism. Transient focal cerebral ischemia Wistar rat model was established through middle cerebral artery occlusion. The cerebral I/R injury rats were treated with intraperitoneal injection of ligustrazine (1, 3, and 10 mg/kg). Human amniotic epithelial cells (HAECs) were treated with ligustrazine (1, 10, 100 μM) and PI3K inhibitor wortmannin (100 μM), following oxygen–glucose deprivation (OGD) treatment. The expression levels of protein kinase B (PKB or AKT), phospho-Akt (p-Akt), endothelial nitric oxide synthase (eNOS), and phosphor-eNOS (p-eNOS) in HAECs and brains of rats were measured by Western blot. The levels of nitric oxide (NO) in HAECs were measured by Griess method using NO2−/NO3− Assay Kit. Infarct volume and neurological deficits were evaluated 24 h after reperfusion. The levels of NO, p-Akt/Akt, and p-eNOS/eNOS in HAECs were significantly reduced after OGD, but ligustrazine treatment increased the levels of those factors in a dose-dependent manner, while those increases were reversed by PI3K inhibitor wortmannin. Similarly, p-Akt/Akt and p-eNOS/eNOS in brain tissue of rats with I/R were significantly reduced compared with control group ( p < 0.05), but ligustrazine treatment increased the levels of p-Akt and p-eNOS in a dose-dependent manner ( p < 0.05), while those increases were also reversed by using wortmannin. Ligustrazine also improved the damage of rat brain tissue caused by I/R, but wortmannin reversed the improvement. Ligustrazine plays a neuroprotective role in rats with cerebral I/R injury through the activation of PI3K/Akt pathway.

Background/Aims: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. Methods: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expressing cells was recorded by Cell Counting Kit-8. Effects of H7N9/NS1 on cellular senescence were investigated by senescence-associated β-galactosidase (SA-β-gal) staining, immunofluorescent staining of phosphorylated heterochromatin protein 1γ (pHP1γ) and qPCR analysis of IL-6 and IL-8. Results: H7N9/NS1 in Neuro2a cells and primary cultured mouse cortical neurons increased the expression of iNOS and boosted NO release. Neuro2a cells constitutively expressing NS1 displayed a reduced proliferative ability, enhanced SA-β-gal staining, increased level of IL-6 and IL-8 and a typical punctuate structure of pHP1γ in nuclei. In addition, p38 MAPK was elevated in NS1-expressing Neuro2a cells. Reduced iNOS expression and subdued cellular senescence effect was found in p38 MAPK inhibitor-treated NS1-expressing Neuro2a cells. Conclusion: Our results suggest that H7N9/NS1 protein increases the iNOS expression and NO release in Neuro2a cells, which can induce cell growth arrest and cellular senescence.

Le but de ce travail est d’étudier deux dimensions sémiologiques, identifiées dans la littérature comme associées au trouble dépressif résistant, l’anxiété et l’apathie. Ces marqueurs cliniques et leurs corrélats radiologiques seront ensuite testés dans une analyse longitudinale du pronostic à 6 mois d’une cohorte de patients souffrant de dépression. Les données originales de ce travail sont issues de la cohorte LONGIDEP. Cette étude prospective, naturalistique, a été menée chez des patients souffrant d’un épisode dépressif majeur qui bénéficiaient, dans le cadre des soins courants, d’une évaluation clinique, neuropsychologique et d’une imagerie cérébrale à l’inclusion. Une nouvelle évaluation a été proposée à 6 mois de l’inclusion. Cette étude nous a permis de montrer que 1) l’apathie dans la dépression est associée à un profil clinique et physiopathologique spécifique, 2) l’analyse catégorielle et sémiologique de l’anxiété dans une population de sujet déprimés résistants n’étaient pas concordantes. Les déprimés résistants présentaient une hyperperfusion amygdale centro-médiane, 3) l’anxiété trait, un pattern cognitif associé à la mémoire visuo-spatiale étaient prédictifs d’une évolution péjorative de la dépression. Des anomalies structurales de régions impliquées dans la régulation émotionnelle et plus précisément l’adaptation au danger/peur, étaient associées à une évolution péjorative de la dépression. Des deux dimensions sémiologiques étudiées, l’anxiété apparaît être impliquées dans le pronostic de la dépression. L’étude des liens entre l’anxiété et les troubles de la motivation est une perspective de recherche pour la dépression résistante
The aim of this work is to study anxiety and apathy in treatment resistant depression. These clinical factors and its imaging correlates will be tested in prediction of outcome in a 6-months follow-up. Original data were retrieved in LONGIDEP cohort. This is a prospective study conducted in routine care. Patients suffering from a mood depressive episode benefited from a clinical, neuropsychological and brain imaging. They were assessed once again at 6 months. Our study has shown that 1) apathy in depression is associated with specific clinical and pathophysiological patterns, 2) categorical and dimensional approach of anxiety in treatment resistant depression are not convergent. This latter population exhibited higher brain perfusion of centro-medial amygdala, 3) trait anxiety, cognitive patterns of visuospatial memory were predictive of pejorative outcome. Structural abnormalities in key regions involved in emotion regulation were associated with pejorative outcome of depression. Only anxiety was involved in outcome of depression. The link between anxiety and motivation should be studied in further works

Nombre de personnes âgées, a placé le vieillissement cérébral et ses pathologies associées dans lesdéfis majeurs de ce début de XXIème siècle. Ce travail de thèse consiste à étudier et quantifierl’impact de la consommation de cigarette sur le vieillissement morphologique cérébral au seind’une grande cohorte de volontaires sains, celle de l’étude 3 Cités. Nous nous sommes attachés àévaluer et comparer son impact, par rapport à d’autres facteurs accélérant le vieillissementcérébral, dans des études transversales et longitudinales. Il en ressort que le tabac à un effet,principalement global, plus important que les facteurs de risque cardiovasculaires inclus dans cetteétude, et de même ampleur que celui de l’âge. Nous montrons que cet effet est arrêté avec laconsommation, montrant qu’une prévention chez les personnes âgés pourrait s’avérer d’un bénéficemajeur pour la société. De plus, les analyses ont été réalisées en séparant les femmes et leshommes dans nos analyses. Cela nous a permit de mettre en évidence une influence différentiellede la consommation de tabac sur le vieillissement cérébral dans les deux sexes.Néanmoins, les résultats présentés ont pour la plupart jamais été montrés et cela demande laréplication de l’étude dans une autre population
The increase in life expectancy seen during the XXth century, followed by an increase in theproportion of elderly, placed the study of brain aging and of its accompanying diseases in thespotlight. This thesis had for goal the study and quantification of the impact of tobaccoconsumption on brain morphological aging in a large cohort of elderly subjects from the Three CitiesStudy. We focused to evaluate and compare its impact, in comparison with other factors known toinfluence brain aging, in longitudinals and cross-sectionals studies. We show that tobacco smokinghas an effect, mainly global, more important than the others cardiovascular risk factors included inthis study and as important as the effect of age. Also, we have found that this effect stops with theconsumption, showing that prevention among the elderly population might be of major interest forsociety. Moreover, analysis have been conducted in men and women separately, allowing us to finddifferential effects of tobacco consumption on the brain morphological aging in the two sexes

This dissertation explores the analysis and creation of compositions from the standpoint of texture and momentum. It is comprised of four chapters. The first presents a number of concepts as tools for analysis, including textural typography and transformation, perception of time and psychological engagement of an audience, and respiration as a metaphor for musical momentum. The second and third chapters apply these tools to Gerard Grisey's "Periodes" and "Partiels," and Brian Ferneyhough's "Lemma-Icon-Epigram." The fourth explores specific methodologies used in composing my dissertation piece, "Phase," including the application of number systems ranging from formal to local levels.

Krossade drömmar där kris och sorg möts•En kvalitativ studie om vilket stöd föräldrar får vars barn hjärnskadats under förlossningenSitnik, Magdalena. Krossade drömmar där kris och sorg möts – en kvalitativ studie om vilket stöd föräldrar får vars barn hjärnskadats under förlossningen. Examensarbete i socialt arbete, 15 högskolepoäng. Malmö högskola: Fakulteten för hälsa och samhälle, institutionen för Hälsa och samhälle, 2016.Många föräldrar som väntar barn drömmer och skapar en mental bild av sitt ofödda barn. Alltså när det händer att ett barn hjärnskadas under förlossning kan föräldrar befinna sig i en kris och sorgesituation. Studien visar att det inte är så många barn som hjärnskadas i samband med förlossningen årligen i Sverige. Därför har syftet med min studie varit att utforska vilket stöd de föräldrar får vars barn hjärnskadats under förlossningen. Den här studien undersöker vilket stöd professionella på neonatalklinikerna upplever att dessa föräldrar är i behov av. Studien illustrerar även hur professionella tillgodoser dessa individers behov och hur föräldrarna bemöts av yrkesverksamma personer på neonatalklinikerna. Studiens resultat visar att kris och sorgeprocess liknar samt överlappar varandra. Både kris och sorg är inte tidsbunden och kan saktas när och även dra sig tillbaka i sina respektive stadier. Resultat visar även att professionella inom neonatalkliniker måste ha individuellt förhållningssätt gentemot sina klienter. Där de erbjuder både praktiskt såväl som sociopsykologiskt stöd och hjälp till föräldrar varvs barn hjärnskadades i samband med förlossning. De yrkesverksamma personerna tillgodoser dessa föräldrarnas behov genom att lyssna på deras individuella behov noggrann. Resultatet pekar även på vikten av samverkan mellan professioner och organisationer för att erbjuda bästa möjliga hjälp för dessa föräldrar. Nyckelord: drömbarn, föräldrar, funktionshindrad, hjärnskada under förlossning,kris, det ickeperfekta barnet, sorg.
SHATTERED DREAMS WHEN CRISIS AND SORROW MEET• A QUALITATIVE STUDY ABOUT WHAT SUPPORT PARENTS TO BRAIN DAMAGED CHILDREN DURING DELIVERY GETSitnik, Magdalena. Shattered dreams when crisis and sorrow meet - a qualitative study about what support parents to brain damaged children during delivery get with a focus on parents. Examination paper in social work, 15p. Malmö University: Faculty of health and society, Department of health and society, 2016.Many parents who are expecting a child dream and create a mental image of their unborn baby. So when the parents are told that their new born child has got brain damage during delivery, parents end up in a situation of crisis and sorrow. The study shows that there are not many children who are brain damage during delivery in Sweden on a yearly basis. Therefore, the purpose of the study has been to explore what support parents to brain damaged children during delivery get.This study explores what support professionals in neonatal clinics experience that parents whose children are brain injured during delivery are in need of. My study also illustrates how professionals meet these needs of individuals and how they treat and respond to those parents in neonatal clinics.Study results show that the crisis and the grief process are similarly and can merge into each other. Both the crisis and grief is not time-bound and can be slowed and also pull back in their respective stages. Results also show that professionals in neonatal clinics must have an individual approach towards their clients. They offer practical as well as socio-psychological support and assistance for these parents whose children are brain injured during delivery. The professionals meet the parents’ needs by listening to them carefully. The results also point out the importance of cooperation between professions and organizations to provide the best possible help for those parents. Keywords: brain damage during birth, disabled, crisis, dream child, grief, not perfect child, parents.

While researchers have explored many important aspects of living with childhood cancer, including the multitude of strains on family members and their reactions, very little is known about the experiences of children with brain tumours and their parents. Grounded theory methods were utilized to explore the unique and shared elements of the experiences of childhood brain tumours, from the perspectives of these children and their parents. Woven throughout their stories were expressions of grief and uncertainty related to the tumour and its effects on their lives. Children and parents tried to maintain a positive outlook and a sense of normalcy, in order to cope and to adapt to the struggles and the changes in their lives. A substantive theory of Balancing Grief and Survival was developed, offering a lens through which to view the children’s and parents’ complex experiences, struggles and coping strategies as integrated, dynamic processes.

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Richard and Nancy's son Jason has been in a car accident and suffered a brain-injury. Yesterday, he woke up from his coma, and he's finally home. Now, Richard and Nancy are forced to face one another, to deal with the blame they level at each other, the guilt they feel, and more importantly, their completely counter views on Jason's recovery. As they try to fight to get their son into the Shepherd Center, one of the best brain-injury rehab centers in the country, they must defend their home from Nancy's sister, Carol, her husband, Rick, and the secret they bring with them. Nancy and Richard must come to terms with their son's injury, forgive each other, and discover the truth of what really happened the night of the accident.
2031-01-01

Les progrès dans le domaine de la neuroimagerie cérébrale ont permis une certaine compréhension des maladies mentales comme la schizophrénie. Cependant, peu de résultats sont cohérents et ils sont souvent contradictoires, ce qui rend difficile de tirer des conclusions concrètes par rapport à la maladie. Plusieurs facteurs jouent un rôle dans les résultats divergents et convergents : Les différentes techniques d'imagerie et les analyses, le nombre de patients inclus dans les études, l'âge des patients, l'âge de l’'apparition de la maladie, les critères de diagnostic, les effets du traitement antipsychotique, le statut social, ainsi que les comorbidités, font partie de ces facteurs. Bien que les différences cérébrales entre femmes et hommes « normaux » sont bien établies, ce n’est que ces dernières années que des études en neuroimagerie de la schizophrénie ont abordé les différences homme-femme comme une explication potentielle des résultats discordants de l’imagerie cérébrale. L'objectif de cette thèse est de comprendre le rôle du sexe (genre féminin et masculin) dans les anomalies anatomiques observées dans la schizophrénie; ceci, en réalisant des études qui contrôlent, autant que possible, l'effet de différentes variables confondantes et en utilisant des analyses d’IRM automatisées chez des patients et des sujets sains de même âge et du même sexe. Une brève revue globale des résultats actuels dans le domaine de la schizophrénie ainsi que des résultats liés aux différences entre les sexes dans la schizophrénie vont être présentés. La première étude visait à étudier l'influence des différences de sexe sur des mesures de la gyrification corticale de la schizophrénie. Étant donné que la schizophrénie est une maladie dont les «symptômes cliniques » ont un impact négatif sur la qualité de vie des patients qui en souffrent, nous avons exploré la relation entre la gyrification corticale et les différents symptômes de la schizophrénie chez les hommes et les femmes atteints de ce trouble psychiatrique. Le rôle du sexe sur la gyrification corticale et son association aux symptômes a été à peine étudié chez les patients atteints de schizophrénie ; c’est pour cette raison que, nous croyons que cette étude est d’une importante valeur. Dans cette première étude, des images 3T T1 ont été acquises auprès de 48 patients atteints de schizophrénie (24 hommes [SZ-M] et 24 femmes [SZ-F]) et 48 volontaires sains (24 hommes [NC-M] et 24 femmes [NC-F]), appariés en fonction de l'âge et du sexe. Des mesures d’indice de gyrification (IG) pour chaque hémisphère et les quatre lobes cérébraux (frontaux, temporal, pariétal, et occipital) ont été effectuées en utilisant le pipeline de CIVET, lequel est entièrement automatisé. Plusieurs résultats intéressants ont émergé: les patients avaient des valeurs inférieures importantes de l’IG global par rapport aux témoins; SZ-M avaient des valeurs d'IG hémisphériques significativement inférieurs par rapport à NC-M, cela n'a pas été observé dans les groupes de femmes. Aucune différence entre les sexes dans les valeurs de diminution de l’IG avec l'âge n’a été observés chez les témoins sains par contre, une diminution de la valeur de l’IG avec l’âge chez les patients était plus importante chez les patients homme que les patients femmes. Une détérioration plus progressive dans l'hémisphère droit dans les deux groupes de patients a été observée, tout comme des réductions significatives des valeurs d’IG en relation avec la durée de la maladie chez SZ-M, mais pas chez SZ-F. Dans les groupes de patients, on observe des diminutions des valeurs d’IG dans les lobes frontaux bilatéraux et, le lobe occipital droit; le groupe SZ-M a montré une valeur d’IG significativement plus élevée par rapport à NC-M dans le lobe temporal droit; SZ-F a montré des valeurs d’IG significativement plus faibles dans les lobes bilatéraux frontaux, temporaux, pariétaux et le lobe occipital droit, par rapport à NC-F. Aucune corrélation significative n'a été trouvée entre les valeurs de l'IG et le profil de la symptomatologique dans les deux groupes de patients. Etant donné que l’IG reflète, en partie, des altérations dans le développement et la connectivité cérébrale, la diminution de l’IG observée chez les patients est en accord avec le modèle de développement neurobiologique de disconnectivité dans la schizophrénie. De plus, nous soulignons l'importance de l'âge ainsi que la durée de la maladie lorsque nous comparons les hommes et les femmes atteints de schizophrénie. Cependant, nous n'avons pas observé de corrélation significative n'a été trouvée entre les valeurs de l'IG et les symptômes, ce qui est d'un intérêt particulier et inattendu compte tenu des résultats de la neuroimagerie montrant par exemple certaines corrélations entre les symptômes positifs et certaines anomalies du lobe temporal dans la schizophrénie. Considérant ces résultats, nous avons décidé d'investiguer, dans notre deuxième étude, l'association entre les symptômes et les densités de matière grise (DMG) et de matière blanche (DMB) à la place des mesures de gyrification corticale. Nous avons utilisé la morphométrie basée sur le voxel "Voxel Based Morphometry (VBM8.0 with Diffeomorphic Anatomical Registration (Through Exponentiated Lie Algebra [DARTEL])" et la modélisation linéaire automatique (SPSS21.0 ALM) sur les images 3T T1 MPRAGE acquises auprès de 40 patients atteints de schizophrénie (SZ) et 41 témoins sains (NC). Nous avons trouvé que les patients atteints de schizophrénie avaient une DMG réduite dans le cortex cingulaire antérieur, le cortex temporal médian gauche et une DMG plus élevée dans le cortex cingulaire postérieur gauche par rapport aux sujets sains. Une diminution significative de DMB dans la région fronto-rectal inférieure gauche et la région pariétale postérieure gauche a été observée chez les patients comparés aux sujets sains. Nous avons trouvé des corrélations positives entre les symptômes positifs et la DMG dans l'insula gauche et le noyau caudé droit; et entre les symptômes négatifs et la DMG dans le cortex frontal médian droite et le lobe postérieur de cervelet droit. Nous avons aussi trouvé des corrélations négatives de DMG dans la région pariétale droite (précuneus), le lobe postérieur du cervelet gauche et les symptômes positifs; ainsi qu'entre la DMG du lobe antérieur du cervelet gauche et les symptômes négatifs. En outre, des corrélations positives ont été trouvées entre la DMB dans le cortex frontal médian droit et les symptômes positifs et entre le DMB dans la région frontale supérieure droite et les symptômes négatifs. Des corrélations négatives ont été trouvées entre les symptômes positifs et la DMB dans la région occipitale inférieure droite et le cunéus occipital droit, tandis que des corrélations négatives ont été trouvées entre la DMB et la région frontale supérieure gauche. Il est intéressant de noter que lorsque les symptômes ont été analysés par regroupement, nous avons trouvé que le symptôme de la désorganisation conceptuelle corrélait positivement avec la DMG totale et la DMB totale. L’augmentation de DMG a été associée à une diminution de la gravité des hallucinations et du manque de spontanéité; tandis que l'augmentation de DMB totale a été associée à la diminution de la sévérité de l'hostilité et des idées de grandeur. Une comparaison entre les groupes d'hommes a montré une diminution de la DMG chez les patients schizophrènes, tandis qu’aucune différences n’a été observée dans les groupes de femmes. Nous n’avons trouvé aucune corrélation entre la DMG, la DMB, le liquide cérébro-spinal, le volume total du cerveau, les symptômes individuels et la schizophrénie chez les sujets féminins. Chez les hommes atteints de schizophrénie, on observe des corrélations négatives importantes entre les idées de grandeur et la DMB; des corrélations positives entre la désorientation et la DMB. De plus on observe des corrélations entre et les déficits d'attention et de DMG et DMB. Nos résultats montrent que ces associations sont différentes chez les hommes et les femmes atteints de la schizophrénie. La symptomatologie de schizophrénie est un mélange de déficits cognitifs et socio-affectifs. Dans ce contexte, le but de notre troisième étude est d'étudier chez les patients atteints de la schizophrénie des DMG et DMB et leur relation avec l’acuité mnésique avec des contenus émotionnelles (négatives, positives et neutres) ainsi que étudier l'effet des différences de sexe sur nos résultats. Quarante et un patients droitiers, traités par antipsychotique, souffrant de schizophrénie (SZ) et 40 témoins sains (NC), tous droitiers, ont participé à l’étude. Nous avons utilisé des images de l'International Affective Picture System (IAPS), une banque d'images émotionnelles, et de l’IRM. On observe chez les témoins sains des corrélations entre les valeurs élevées de DMG du cortex pariétal postérieur, du lentiform, du putamen, noyau caudé, le cortex orbitofrontal inférieur gauche et la reconnaissance des images négatives. On observe des corrélations entre la DMG dans la région temporale gauche, fusiforme et la reconnaissance des images positives ; et également dans le cervelet antérieur gauche et l’acuité des images neutres. Chez les patients on observe des valeurs élevées des DMG dans le cortex occipital inférieur gauche et la reconnaissance des images négatives, mais aucune corrélation entre la capacité de reconnaissance des images positives ou neutres. Nous avons observé chez les témoins sains: des relations significatives entre la DMB dans le cortex pariétal postcentral gauche et la capacité de reconnaître des images négatives; dans le cortex temporal inferieur gauche, le cortex pariétal gauche (précuneus), le cortex frontal gauche et la capacité de reconnaissance des images positives; des valeurs de DMB du cortex temporel médian et l’acuité des images neutres. Les patients atteints de schizophrénie ont montré des relations significatives entre de DMB dans le cortex occipito-lingual gauche et la reconnaissance des images négatives ; dans le cortex pariétal angulaire gauche et la reconnaissance des images positives ; et dans le cortex temporal supérieur droit et les images neutres. Les différences de sexe dans la schizophrénie ont été observées : chez les patients de sexe masculin, des corrélations négatives ont été trouvées entre les DMB et la capacité de reconnaître des images négatives et positives. Chez les hommes sains, nous avons trouvé des corrélations positives entre des valeurs totales de DMG et la capacité de reconnaître des images négatives. Nous n’avons pas observé de corrélations dans les groupes de femmes. Ces résultats soutiennent l'hypothèse de l'atrophie fronto-temporale régionale chez les patients schizophrènes. Toutefois, nous notons qu’ils ont des augmentations relatives des valeurs de DMB dans le cortex occipito-pariétal. Nous avançons l'hypothèse que les déficits mnésiques chez les patients sont liés à des perturbations dans la coordination des réseaux cérébraux, ce qui peut être affecté par des déficits structuraux plus évidents chez les patients masculins. Par conséquent, nous préconisons que les futures études devraient utiliser le connectome ou l’approche « réseaux cérébraux » pour étudier l’impact du sexe (genre masculin-féminin) sur les déficits cognitifs et symptomatologiques dans la schizophrénie. Nos résultats globaux soulignent l'importance de la différence entre homme et femme dans la modulation de manifestations cliniques et fonctionnelles de la schizophrénie. Ainsi, nous croyons que le contrôle des covariables comme l'âge, la durée de la maladie et le statut social est insuffisant et que les études futures sur la schizophrénie devraient systématiquement séparer les hommes des femmes, afin de mieux comprendre cette maladie mentale complexe et dévastatrice.
Advances in cerebral neuroimaging techniques have helped our understanding of mental illnesses, such as schizophrenia. Few findings remain consistent and are often contradictory, making it difficult to draw informative conclusions about the disease. Several factors play a role in both diverging and converging results. Imaging technique and analyses, number of patients involved, age of patients, age at onset of the disease, diagnostic criteria, antipsychotic treatment effects, social status, comorbidities, are among some of the reasons. Despite well established cerebral sex differences in healthy population, it is only in recent years that neuroimaging studies in schizophrenia have addressed sex differences as a major possible explanation for discrepant neuroimaging finding. The aim of this thesis is to help understand the role of sex on brain structures in schizophrenia, by conducting studies that control as much as possible for other variables and by using MRI automated analyses for patients and controls matched for age and sex. This work will briefly present findings in schizophrenia in general, and then an extensive review of the literature on sex differences in schizophrenia will be presented. From it, we are able to conclude that sex differences have been reported with rare exception in almost all aspects involved in the life of patients with schizophrenia. Chapters 1. The first study investigated sex differences in cortical gyrification in schizophrenia patients (SZ). In addition, considering that schizophrenia is a disease of “clinical symptoms” that determine the quality of life of patients afflicted by it, we explored the relation between cortical gyrification and symptoms in males and females with schizophrenia. The role of sex on cortical gyrification and its association with symptoms has been scarcely investigated in patients with schizophrenia. In this study, 3T T1 images were acquired from 48 schizophrenia patients (24 males [SZ-M] and 24 females [SZ-F]) and 48 normal controls [NC] (24 males [NC-M] and 24 females [NC-F]) matched for age, sex, and handedness. Gyrification Index (GI) analyses for each hemisphere and four cerebral regions (frontal, temporal, parietal, and occipital) were performed using the fully automated CIVET pipeline. Patients had significant lower values of the overall GI relative to normal controls and SZ-M had significant lower right hemispheric GI values compared to NC-M. This was not observed in either NC-F or in SZ. No gender difference in GI values decreases with age were observed in NC. In patients, GI decreases with age were greater in SZ-M than SZ-F, with a more progressive deterioration in the right hemisphere in both patient groups. Significant GI value reductions in association with duration of illness were observed in SZ-M but not in SZ-F. Patient groups had lower GI in bilateral frontal, temporal, and parietal lobes than controls. SZ-F had significant lower GI values in left frontal, bilateral temporal and left parietal lobe compared to NC-F. No significant correlations were found between GI values and symptom scores in either group of patients. Since GI reflects, in part, alterations in cerebral development and connectivity, the decrease in GI observed in patients is in agreement with the neurodevelopmental model of disconnectivity in schizophrenia, and may explain the worse prognosis and social outcome observed in male patients. Furthermore, we emphasize the importance of age and duration of illness when comparing males and females with schizophrenia. Observed differences between male and female patients may reflect a more diffuse and generalized cortical loss in males. Female patients had cortical loss in specific regions, while preserving cortical gyrification in compensatory regions. Our latter finding -no significant correlation between GI values and symptom scores- was of particular interest and was unexpected in view of neuroimaging findings of correlations between positive symptoms and temporal lobe abnormalities. 2. In the second study, we examined the association between symptoms and brain structure using gray (GMD) and white matter (WMD) densities. Voxel-based morphometry (VBM8.0 with Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra [DARTEL]) and Automatic Linear Modeling (SPSS21.0 ALM) were used on 3T T1 MPRAGE images acquired from 40 schizophrenia patients (SZ) and 41 normal controls (NC). We found that SZ had lower GMD in the anterior cingulate cortex and left middle temporal gyrus, and higher GMD in the left posterior cingulate in comparison to NC. SZ had significantly lower WMD in the left inferior fronto-rectal and the left posterior parietal regions in comparison to NC. Significant positive correlations were found between positive symptoms and GMD in the left insula and right caudate, and between negative symptoms and GMD in the right middle frontal and the posterior lobe of the right cerebellum (uvula). Inverse relationships between GMD in the right parietal (precuneus), the left posterior lobe of the cerebellum (uvula) and positive symptoms, and between GMD in the left anterior lobe of the cerebellum and negative symptoms were observed in SZ. In addition, positive correlations were found between WMD in the right middle frontal lobe, and between positive symptoms and WMD in the right superior frontal region with negative symptoms. Negative correlations were found between positive symptoms and WMD in the right inferior occipital and the right occipital cuneus, while negative symptoms correlated negatively with the WMD of the left superior frontal. When symptom clusters were analyzed, conceptual disorganization symptom positively correlated with both total GMD and WMD. While increases in GMD were associated with decreased severity of lack of spontaneity and hallucinations symptom, increases in total WMD were associated with decreased severity of hostility and grandiosity symptoms. Comparison between male subjects revealed decreased GMD in male schizophrenia patients, while no differences were observed between females across groups. No correlations were found in female groups between GMD, WMD, CSF, or total brain volume and individual symptoms. In males with schizophrenia, significant negative correlation between ideas of grandiosity and WMD, a positive correlation between disorientation and WMD, and attention deficits and GMD and WMD were found. The current data suggest region-specific GMD and WMD association with negative and positive symptoms. In addition, it reveals that such associations are different in male and female schizophrenia patients. 3. The third study investigated the relationships of GMD and WMD with memory accuracy for emotionally negative, positive, and neutral pictures in schizophrenia patients relative to normal controls. Schizophrenia is characterized by an amalgam of cognitivo-socio-emotional deficits. The relationship between emotion processing on cognition and neurobiological underpinnings merit more attention than it has received so far. Memory deficits are among the most common deficits in schizophrenia and have a widespread impact on cognition in general. Additionally, consistently with the major theme of the present thesis, we investigated the effect of gender on the observed effect. Forty one, right-handed medicated patients with schizophrenia (SZ) and 40 right-handed normal controls (NC) matched by age and sex were assessed for memory accuracy using negative, positive and neutral pictures taken from the International Affective Picture System (IAPS). Imaging methods and analyses were similar to our second study. Fifteen minutes after presentation of selected IAPS images (incidental encoding), subjects were asked to recognize the previously seen images among other images. We found higher GMD in NC in the right posterior parietal cortex, lentiform, putamen, and caudate, as well as the left inferior orbitofrontal cortex, in relation with the negative images accuracy. NC had higher GMD in the left temporal and fusiform regions in relation with the positive images accuracy, and higher GMD in the left anterior cerebellum in relation with neutral images. Schizophrenia subjects had higher GMD in the left inferior occipital cortex in relation with the negative images accuracy, but GMD was not correlated with positive or neutral images accuracy in this group. WMDs correlations were higher in NC in the left postcentral parietal region for negative images; in the left inferior temporal, left precuneus parietal, and left frontal regions for positive images; and in the left middle temporal region for neutral images. Schizophrenia patients had higher WMD in the left lingual occipital for negative images; in the left angular parietal for positive images; and in the right superior temporal region for neutral images. While examining the two sexes separately, we observed inverse correlations between WMD and both negative and positive pictures in male patients. In addition, only in male controls, GMD positively correlated with negative pictures and this correlation was absent in female SZ subjects and NC females. These findings support the hypothesis of fronto-temporal regional atrophy in schizophrenia. Schizophrenia patients have relatively increased occipito-parietal WMD, advancing the hypothesis that the core pathophysiological problem underlying recall memory in SZ may be related to disruptive alterations in the coordination of large-scale brain networks, and this may be affected by structural deficits that are more evident in male patients. It is recommended that future studies should use the connectomes or the brain networks approach to investigate the effect of sex on memory deficits in schizophrenia. Our overall findings point out to the importance of sex in modulating the clinical and functional manifestations of schizophrenia. We believe that controlling for covariates as age, duration of illness, social status, etc. is insufficient and that future studies in schizophrenia should systematically separate male and female findings, if we wish to understand this complex and devastating mental illness.

This chapter demonstrates how the cortex communicates with the basal ganglia and the thalamus progressively during the evolution of vertebrates. The telencephalic loop is involved in social behaviour and cognitive processes. In mammals, the telencephalic loop, in which the cortex now replaces the pallium, takes a leading role in controlling behaviour. Thus, the telencephalon, a very minor input of the basal ganglia in anamniots, gradually becomes the main input as evolution progresses. Ultimately, the resulting neural network possesses the same dynamic properties as those described in Chapter 5. The neural network is also able to perform reinforcement learning through the subcortical loop, and also to automatize some skills at the cortical level.

Abstract I am the mother of three sons, but only one lives. Every component of my life as a mother was a shock: I never could have imagined that my first son would be born with profound brain damage; never could dream that my second would as well. I could never have conceived that my eldest would die, and couldn’t have ever considered that my second one would, too. I could never imagine the life I’d lead as their mother, and how I’d go forward after their deaths. I could never apprehend how many losses I’d experience before I lost them forever. I am the mother of three sons but travel the world with only one, carrying the absence of my other two with me as I step into my future.

A network of interconnected computers, or “computational grids,” can facilitate the ability of users to complete complex computational tasks that would be virtually impossible with a single computer. By leveraging the computational strength of grids, individual users can efficiently disseminate, exchange, and retrieve information as easily as if it were stored locally. As the authors found in this study, the possibilities computational grids present for highly specialized medical fields such as neuro-oncology are limitless. By harnessing the power of grids, neuro-oncologists can link to sophisticated interactive medical images around the world, perform complicated statistical analyses, create larger collaborative research projects, and improve delivery of care to patients around the globe. Thus, utilization of grid computing modules will inevitably lead to marked improvements in clinicians’ ability to detect, manage, and prevent complications associated with brain tumors.

Invasive extraoperative EEG using subdural grids and strip electrodes is indicated for well-selected patients with suspected temporal lobe epilepsy (TLE) to confirm and delineate the epileptogenic zone prior to resection. This chapter discusses indications, hypothesis, and strategy for implantation of subdural electrodes. The emphasis is on a practical approach, with patients with MRI-negative and MRI-positive TLE being discussed separately and with a number of illustrative cases being presented.

In this chapter, we explore the neuroscience of grief and grieving. Even though the cognitive portion of the initiation into loss implores us to see a correlation between what is expected of us and the concept of reality as we move toward the outcome, the brain is meaning-driven, attempting to match new information with prior understanding. And as neural connections continue to develop and change throughout grief and grieving the “emotional monster” may not be capable of being quieted through support, whether professional or personal. The resistance from a cognitive approach is taken over by our effort to tame that “emotional monster” and images and feelings that are unique to the loss process stunt the capability of the brain to provide rational thinking. We end by picturing how our relentless search began, as we are in awe of what we intuitively know to be true, and that we are not fixed in toxicity, but can change the most challenging neurological situation. Our search was to understand the process of cognition as we move through grief and grieving. We wrote this chapter hoping it would shed a well-lit conversation on the most difficult time we will experience in our lives, the initiation into loss. The light shines on the neuroscience of this journey – as it would not honor ‘self' if we did not look at ‘self ‘in a wholesome way. We frame this chapter through four focus lenses: self and self-discovery focus; emotion focus; social context and role identity focus; and cognitive focus.

Abstract Microbubble enhanced High Intensity Focused Ultrasound (HIFU) is of great interest to tissue ablation for tumor treatment such as in liver and brain cancers, in which ultrasonic contrast agent microbubbles are injected to the targeted region to promote local heating while reducing pre-focal damage. To accurately characterize the acoustic and thermal fields during this process, a compressible Euler-Lagrange model is used. The non-linear ultrasound field is modeled using compressible N-S equations on an Eulerian grid, while the microbubbles are tracked as discrete singularities in a Lagrangian fashion with their dynamics computed. Their intimate coupling is realized through the local void fraction, which is computed from the instantaneous bubble volumes and locations, and then fed to the fluid continuum model. Owing to demanding computational cost in real applications, schemes for significant speedup are highly desirable. We present here a MPI parallelization scheme based on domain decomposition for both the continuum fluid and the discrete bubbles. The Eulerian computational domain is subdivided into several subdomains having each the same number of grids, while the bubbles are subdivided based on their locations corresponding to each subdomain. During each computation time step, MPI processors, each handling one subdomain, are 1) first used to execute the fluid computation, and 2) then to execute the bubble computations, 3) followed by the coupling procedure, which maps the void fraction from the Lagrangian bubble solutions into the Eulerian grids. Steps 1) and 2) are relatively straightforward by routinely following regular MPI procedures. However, step 3) becomes challenging as the effect of the bubbles through the void fraction at an Eulerian point near a subdomain border will require information from bubbles located in different subdomains. Similarly, a bubble near a border between subdomains will spread its contribution to the void fraction of different subdomains. This is addressed by a special utilization of ghost cells surrounding each fluid subdomain, which allows bubbles to spread their void fraction effects across subdomain edges without the need of exchanging directly bubble information between subdomains and significantly increasing overhead. This void fraction implementation is verified by gas volume conservation before and after spreading the bubble effects. Other bubble effects such as thermal effects are handled in a similar way. This parallelization scheme is validated and illustrated on a typical microbubble enhanced HIFU problem, followed by parallelization scaling tests and efficiency analysis.

Intracranial aneurysms are pathological dilations of the arteries in the brain, whose rupture is often fatal. Surgery and endovascular embolization are the two most common methods of treatment. Surgery involves opening a portion of the skull and placing metallic clips at the aneurysm neck thereby preventing blood flow into the aneurysm. In the case of embolization, a catheter is used to pack platinum coils in the aneurysm reducing the inflow and promoting thrombus formation. Due to its less invasive approach endovascular embolization is preferred over surgery. Nevertheless this approach also has some serious aftereffects. Coil compaction followed by the re-growth or the formation of the secondary aneurysm is the most common problem. The endovascular embolization approach also has a serious shortcoming that the coils alone cannot be used to block every type of aneurysm. Wide neck or fusiform aneurysms are coiled with the help of stents. Recent studies show that stent, which is a hollow cylindrical mesh, can be successfully used to limit the flow of blood into the aneurysm. However these studies have been conducted using idealized in-vitro and numerical models. Studies conducted using patient-specific models generated from medical images will provide a more realistic approach to computationally investigate the effects of stents on intra-aneurysmal flow patterns. However generation of computational grids inside the parent vessel and around these stents is a challenging task. In this paper an algorithm to map the stent to a patient-specific vascular model and an adaptive unstructured embedded gridding technique to model flow around stents are presented. Finally these techniques are demonstrated on patient-specific cases to prove their feasibility.

As a student undertaking a Longitudinal Integrated Clerkship (LIC)1 based in a GP practice in a rural community in the North of Scotland, I have been lucky to be given responsibility and my own clinic lists. Every day I conduct consultations that change my practice: the challenge of clinically applying the theory I have studied, controlling a consultation and efficiently exploring a patient's problems, empathising with and empowering them to play a part in their own care2 – and most difficult I feel – dealing with the vast amount of uncertainty that medicine, and particularly primary care, presents to both clinician and patient. I initially consulted with a lady in her 60s who attended with her husband, complaining of severe lower back pain who was very difficult to assess due to her pain level. Her husband was understandably concerned about the degree of pain she was in. After assessment and discussion with one of the GPs, we agreed some pain relief and a physio assessment in the next few days would be a practical plan. The patient had one red flag, some leg weakness and numbness, which was her ‘normal’ on account of her multiple sclerosis. At the physio assessment a few days later, the physio felt things were worse and some urgent bloods were ordered, unfortunately finding raised cancer and inflammatory markers. A CT scan of the lung found widespread cancer, a later CT of the head after some developing some acute confusion found brain metastases, and a week and a half after presenting to me, the patient sadly died in hospital. While that was all impactful enough on me, it was the follow-up appointment with the husband who attended on the last triage slot of the evening two weeks later that I found completely altered my understanding of grief and the mourning of a loved one. The husband had asked to speak to a Andrew MacFarlane Year 3 ScotGEM Medical Student 2 doctor just to talk about what had happened to his wife. The GP decided that it would be better if he came into the practice - strictly he probably should have been consulted with over the phone due to coronavirus restrictions - but he was asked what he would prefer and he opted to come in. I sat in on the consultation, I had been helping with any examinations the triage doctor needed and I recognised that this was the husband of the lady I had seen a few weeks earlier. He came in and sat down, head lowered, hands fiddling with the zip on his jacket, trying to find what to say. The GP sat, turned so that they were opposite each other with no desk between them - I was seated off to the side, an onlooker, but acknowledged by the patient with a kind nod when he entered the room. The GP asked gently, “How are you doing?” and roughly 30 seconds passed (a long time in a conversation) before the patient spoke. “I just really miss her…” he whispered with great effort, “I don’t understand how this all happened.” Over the next 45 minutes, he spoke about his wife, how much pain she had been in, the rapid deterioration he witnessed, the cancer being found, and cruelly how she had passed away after he had gone home to get some rest after being by her bedside all day in the hospital. He talked about how they had met, how much he missed her, how empty the house felt without her, and asking himself and us how he was meant to move forward with his life. He had a lot of questions for us, and for himself. Had we missed anything – had he missed anything? The GP really just listened for almost the whole consultation, speaking to him gently, reassuring him that this wasn’t his or anyone’s fault. She stated that this was an awful time for him and that what he was feeling was entirely normal and something we will all universally go through. She emphasised that while it wasn’t helpful at the moment, that things would get better over time.3 He was really glad I was there – having shared a consultation with his wife and I – he thanked me emphatically even though I felt like I hadn’t really helped at all. After some tears, frequent moments of silence and a lot of questions, he left having gotten a lot off his chest. “You just have to listen to people, be there for them as they go through things, and answer their questions as best you can” urged my GP as we discussed the case when the patient left. Almost all family caregivers contact their GP with regards to grief and this consultation really made me realise how important an aspect of my practice it will be in the future.4 It has also made me reflect on the emphasis on undergraduate teaching around ‘breaking bad news’ to patients, but nothing taught about when patients are in the process of grieving further down the line.5 The skill Andrew MacFarlane Year 3 ScotGEM Medical Student 3 required to manage a grieving patient is not one limited to general practice. Patients may grieve the loss of function from acute trauma through to chronic illness in all specialties of medicine - in addition to ‘traditional’ grief from loss of family or friends.6 There wasn’t anything ‘medical’ in the consultation, but I came away from it with a real sense of purpose as to why this career is such a privilege. We look after patients so they can spend as much quality time as they are given with their loved ones, and their loved ones are the ones we care for after they are gone. We as doctors are the constant, and we have to meet patients with compassion at their most difficult times – because it is as much a part of the job as the knowledge and the science – and it is the part of us that patients will remember long after they leave our clinic room. Word Count: 993 words References 1. ScotGEM MBChB - Subjects - University of St Andrews [Internet]. [cited 2021 Mar 27]. Available from: https://www.st-andrews.ac.uk/subjects/medicine/scotgem-mbchb/ 2. Shared decision making in realistic medicine: what works - gov.scot [Internet]. [cited 2021 Mar 27]. Available from: https://www.gov.scot/publications/works-support-promote-shared-decisionmaking-synthesis-recent-evidence/pages/1/ 3. Ghesquiere AR, Patel SR, Kaplan DB, Bruce ML. Primary care providers’ bereavement care practices: Recommendations for research directions. Int J Geriatr Psychiatry. 2014 Dec;29(12):1221–9. 4. Nielsen MK, Christensen K, Neergaard MA, Bidstrup PE, Guldin M-B. Grief symptoms and primary care use: a prospective study of family caregivers. BJGP Open [Internet]. 2020 Aug 1 [cited 2021 Mar 27];4(3). Available from: https://bjgpopen.org/content/4/3/bjgpopen20X101063 5. O’Connor M, Breen LJ. General Practitioners’ experiences of bereavement care and their educational support needs: a qualitative study. BMC Medical Education. 2014 Mar 27;14(1):59. 6. Sikstrom L, Saikaly R, Ferguson G, Mosher PJ, Bonato S, Soklaridis S. Being there: A scoping review of grief support training in medical education. PLOS ONE. 2019 Nov 27;14(11):e0224325.