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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
The scarcity of Romano-British human remains from north-west England has hindered understanding of burial practice in this region. Here, we report on the excavation of human and non-human animal remains1 and material culture from Dog Hole Cave, Haverbrack. Foetal and neonatal infants had been interred alongside a horse burial and puppies, lambs, calves and piglets in the very latest Iron Age to early Romano-British period, while the mid- to late Roman period is characterised by burials of older individuals with copper-alloy jewellery and beads. This material culture is more characteristic of urban sites, while isotope analysis indicates that the later individuals were largely from the local area. We discuss these results in terms of burial ritual in Cumbria and rural acculturation. Supplementary material is available online (https://doi.org/10.1017/S0068113X20000136), and contains further information about the site and excavations, small finds, zooarchaeology, human osteology, site taphonomy, the palaeoenvironment, isotope methods and analysis, and finds listed in Benson and Bland 1963.
Hydrogen lithography has been used to template phosphine-based surface chemistry to fabricate atomic-scale devices, a process we abbreviate as atomic precision advanced manufacturing (APAM). Here, we use mid-infrared variable angle spectroscopic ellipsometry (IR-VASE) to characterize single-nanometer thickness phosphorus dopant layers (δ-layers) in silicon made using APAM compatible processes. A large Drude response is directly attributable to the δ-layer and can be used for nondestructive monitoring of the condition of the APAM layer when integrating additional processing steps. The carrier density and mobility extracted from our room temperature IR-VASE measurements are consistent with cryogenic magneto-transport measurements, showing that APAM δ-layers function at room temperature. Finally, the permittivity extracted from these measurements shows that the doping in the APAM δ-layers is so large that their low-frequency in-plane response is reminiscent of a silicide. However, there is no indication of a plasma resonance, likely due to reduced dimensionality and/or low scattering lifetime.
OBJECTIVES/GOALS: Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells. Emerging data suggest that differences in intestinal microbiota might be critically involved both in autoimmunity and in glucose homeostasis. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites positively by increasing production of beneficial short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Further, an acetylated and butyrylated form of HAMS (HAMS-AB) that increases beneficial SCFA production, namely acetate and butyrate, has been safe and effective in disease prevention in mouse T1D models. The objective of the proposed study is to assess the effect of administering a prebiotic, such as HAMS-AB, on the gut microbiome profile, SCFA production, glycemia and β-cell function in humans with T1D. METHODS/STUDY POPULATION: We hypothesize that administration of HAMS-AB will (i) improve the gut microbiome profile in humans with T1D, (ii) increase SCFA production, and (iii) improve β-cell health, β-cell function and overall glycemia. We propose a pilot randomized controlled cross-over trial of HAMS-AB in 12 youth with newly-diagnosed T1D. We will use state-of-the-art markers to profile the gut microbiome (using 16S rRNA sequencing), measure stool SCFA levels (using gas chromatography), asses β-cell stress/death (by measuring proinsulin to C-peptide ratios) and glycemia (assessed by continuous glucose monitoring and HbA1c measurements). RESULTS/ANTICIPATED RESULTS: We expect that the use of HAMS-AB in newly diagnosed youth with type 1 diabetes will alter the gut microbiome profile (thus increasing the number of fermenters and SCFA levels), β-cell function and glycemia in humans with T1D. DISCUSSION/SIGNIFICANCE OF IMPACT: Given the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, the use of a prebiotic such as HAMS-AB offers a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.
OBJECTIVES/GOALS: Primary graft dysfunction (PGD) is acute lung injury in the first three days after lung transplant. Patients that experience PGD have increased mortality and an increased risk of chronic lung allograft dysfunction. The pathogenesis is thought to be an ischemia-reperfusion injury but is incompletely understood and there are no specific therapies. We investigated the role of the microbiome in PGD and associations with inflammation and markers of aspiration. METHODS/STUDY POPULATION: We collected airway lavage samples from lung transplant donors before procurement and recipients after reperfusion. We extracted DNA, amplified the bacterial 16S rRNA gene, and sequenced on the Illumina MiSeq platform. QIIME2 and Deblur were used for bioinformatic analysis. R packages were used for downstream analysis and visualizations. The host response was quantified using the Milipore 41-plex Luminex and an ELISA for pepsin. Clinical data was collected by the Penn Lung Transplant Outcomes Group. PGD was assessed by degree of hypoxemia and chest X-ray findings in the 72 hours after transplant. RESULTS/ANTICIPATED RESULTS: There was no significant difference in alpha diversity (Shannon index, p = 0.51), biomass (via comparison of 16S amplicon PicoGreen, p = 0.6), or beta diversity (Weighted UniFrac, p = 0.472, PERMANOVA) between subjects with PGD grade 3 (n = 36) and those that did not (n = 96). On taxonomic analysis, we found an enrichment of Prevotella in donor and recipient lungs that went on to develop PGD (p = 0.05). To follow up this finding we measured immune response and pepsin concentrations in recipient lungs. We found elevated levels in 35/41 cytokines measured in subjects that developed PGD as well as an elevation in pepsin and a correlation between pepsin concentration and Prevotella relative abundance (Figure 1). Additionally, Prevotella relative abundance had statistically significant positive correlations with multiple cytokines such as IL-6 (Pearson’s = 0.26, p = 0.009) and eotaxin (Pearson’s = 0.24, p = 0.016). DISCUSSION/SIGNIFICANCE OF IMPACT: There is an enrichment of oral anerobes in lung allografts that eventually develop PGD. This is associated with elevated levels of pepsin and markers of inflammation. These lines of evidence suggest aspiration contributes to priming the allograft for PGD.
The purpose of this rejoinder is to emphasize several important areas of future research that were mentioned by one or both commentaries. First, the authors discuss issues related to multi-source assessment, such as the importance of further research on informant bias, and argue that the information gleaned from multiple sources is worth the added assessment burden. Second, they underscore the importance of longitudinal assessment both in capturing the treatment-relevant within-person processes through which personality pathology unfolds, as well as tracking therapeutic progress. They assert that a given measure’s ability to reliably and validly measure change over time should be considered when evaluating its clinical utility. Finally, they emphasize the need for greater attention to clinical utility of dimensional PD assessment measures.
The purpose of this chapter is to review the current state of the dimensional assessment of personality disorder (PD). The first part of the chapter serves as a review of the most well-established and commonly used measures of maladaptive personality traits. Measures that assess the psychosocial impairment associated with personality pathology also are reviewed. Areas of discontinuity among these measures (e.g., theoretical origin, method of scale construction, degree of correspondence with well-known trait dimensions, attention received in the empirical literature, degree of bipolarity of underlying dimensions) are emphasized, and the clinical utility of measures is evaluated. The second part of the chapter focuses on several controversial issues with which the field of dimensional PD assessment now is grappling. These issues include (a) the psychometric distinction of personality traits from personality functioning, (b) the incremental utility of adaptive trait assessment, (c) the question of maladaptive trait bipolarity, (d) facet-level differences versus domain-level similarity across competing PD trait models, and (e) the value of multi-source assessment.
Introduction: Prehospital field trauma triage (FTT) standards were reviewed and revised in 2014 based on the recommendations of the Centers for Disease Control and Prevention. The FTT standard allows a hospital bypass and direct transport, within 30 min, to a lead trauma hospital (LTH). Our objectives were to assess the impact of the newly introduced prehospital FTT standard and to describe the emergency department (ED) management and outcomes of patients that had bypassed closer hospitals. Methods: We conducted a 12-month multi-centred health record review of paramedic and ED records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness (physiologic), step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as urgent that met FTT standard, regardless of transport time. We developed and piloted a data collection tool and obtained consensus on all definitions. The primary outcome was the rate of appropriate triage to a LTH which was defined as: ISS ≥12, admitted to intensive care unit (ICU), non-orthopedic surgery, or death. We have reported descriptive statistics. Results: 570 patients were included: mean age 48.8, male 68.9%, falls 29.6%, motor vehicle collisions 20.2%, stab wounds 10.5%, transported to a LTH 76.5% (n = 436). 72.2% (n = 315) of patients transported to a LTH had bypassed a closer hospital and 126/306 (41.2%) of those were determined to be an appropriate triage to LTH (9 patients had missing outcomes). ED management included: CT head/cervical spine 69.9%, ultrasound 53.6%, xray 51.6%, intubation 15.0%, sedation 11.1%, tranexamic acid 9.8%, blood transfusion 8.2%, fracture reduction 6.9%, tube thoracostomy 5.9%. Outcomes included: ISS ≥ 12 32.7%, admitted to ICU 15.0%, non-orthopedic surgery 11.1%, death 8.8%. Others included: admission to hospital 57.5%, mean LOS 12.8 days, orthopedic surgery 16.3% and discharged from ED 37.3%. Conclusion: Despite a high number of admissions, the majority of trauma patients bypassed to a LTH were considered over-triaged, with a low number of ED procedures and non-orthopedic surgeries. Continued work is needed to appropriately identify patients requiring transport to a LTH.
Stigma against mental illness and the mentally ill is well known. However, stigma against psychiatrists and mental health professionals is known but not discussed widely. Public attitudes and also those of other professionals affect recruitment into psychiatry and mental health services. The reasons for this discriminatory attitude are many and often not dissimilar to those held against mentally ill individuals. In this Guidance paper we present some of the factors affecting the image of psychiatry and psychiatrists which is perceived by the public at large. We look at the portrayal of psychiatry, psychiatrists in the media and literature which may affect attitudes. We also explore potential causes and explanations and propose some strategies in dealing with negative attitudes. Reduction in negative attitudes will improve recruitment and retention in psychiatry. We recommend that national psychiatric societies and other stakeholders, including patients, their families and carers, have a major and significant role to play in dealing with stigma, discrimination and prejudice against psychiatry and psychiatrists.
In addition to the positive and negative symptoms, schizophrenia is associated with a variety of cognitive impairments, and in particular with episodic memory deficits. Functional neuroimaging studies have begun exploring the potential neural correlates of memory deficits but there are few reports of structural brain abnormalities underlying memory impairment in schizophrenia. We investigated the potential association between morphological brain abnormalities as revealed by cortical thickness measures and episodic memory performance on a face recognition task. Differences in regional cortical thickness between 27 patients with a DSM-IV diagnosis of schizophrenia and 28 control matched subjects were investigated using MRI T1 images and computer image analysis (CIVET pipeline; Lerch and Evans, 2005). Cortical thickness was estimated as the shortest distance between the pial surface of the cerebral cortex and the white-matter/gray-matter interface surface at numerous points (40 962 vertices) across the cortical mantle. Consistent with previous studies, a group comparison revealed thinner cortex in the patient group relative to controls in the right prefrontal cortex and parahippocampal gyrus. Interestingly, a significant positive correlation between memory performance and cortical thickness of the anterior cingulate, bilaterally as well as the right parahippocampal gyrus was noted in the schizophrenia group. That is, the thinner the cortex in those regions, the more impaired the patients were in terms of memory performance as compared to healthy participants.
L’exercice de la médecine est un compromis permanent entre la vie et la mort, entre puissance médicale et risque d’échec. Un exercice d’autant plus complexe qu’il est soumis aux contraintes d’une organisation institutionnelle mouvante et d’une charge de travail croissante. Par essence, les psychiatres sont exposés à une charge émotionnelle intense dans leurs échanges avec des patients souffrants et traumatisés, d’autant qu’il leur est recommandé de faire preuve d’empathie. Ainsi les médecins présentent un risque important de burn out, avec 49 % d’épuisement émotionnel chez des psychiatres italiens par exemple. Les comorbidités du burn out restent la dépression, le suicide, les addictions. Le risque suicidaire est plus élevé chez les médecins (les hommes médecins sont 1,4 fois plus à risque de commettre un suicide que les hommes non-médecins) et seulement 1/5 déclarent qu’ils iraient chercher de l’aide s’ils souffraient d’une maladie mentale. Etre thérapeute auprès de victimes de traumatismes peut entraîner une souffrance psychologique cumulée se manifestant sous forme de certains symptômes post-traumatiques révélant un traumatisme vicariant ou secondaire. L’usure de compassion, terme parfois utilisé comme synonyme, est pourtant quant à elle conceptualisée comme la somme de deux entités : le trauma vicariant et le burn out. La vulnérabilité à ces modifications cognitives est d’autant plus grande chez les soignants qu’ils présentent une exposition personnelle à des évènements traumatisants importante. L’élaboration d’échelles d’évaluation validées permet de mener des études sur ces différentes dimensions (« usure de compassion », traumatisme vicariant, burn out,…) parfois comprises comme conséquences néfastes de stratégies de coping dépassées. En France, le développement de la prise en soin des victimes de psychotraumatisme, doit conduire à étudier l’impact de celui-ci sur les personnels soignants.
A range of decision-makers, including policy-makers, NGOs and local communities, have a stake in developing conservation interventions that are to be implemented on the ground. In order to ensure that decision-making is evidence-informed, the science community needs to engage these communities of policy and practice effectively. This chapter brings together work which explores how scientists can work effectively with decision-makers, using global case studies from South America, Australia, New Zealand and elsewhere to identify what works. It identifies 10 key tips for successful engagement : (1) know who you need to talk to, (2) engage early, (3) make it easy to engage, (4) include multiple knowledges, perspectives and worldviews, (5) think hard about power, (6) build trust, (7) good facilitation is key, (8) learn new engagement skills, (9) make use of existing spaces of collaboration, and (10) don't give up. While executing these tips will not guarantee successful engagement in every case, it will improve the chances for mutually beneficial relationships and hence better conservation outcomes.
Les patients souffrant de maladies mentales meurent en moyenne 25 ans plus tôt que la population générale. Les causes de mortalité sont notamment liées aux maladies cardiovasculaires, en lien avec le syndrome métabolique. Peu de littérature explore les comorbidités somatiques et psychiatriques dans les Antilles françaises. L’objectif principal de cette étude préliminaire est de décrire au centre de crise du CHU de Martinique la population hospitalisée sur le plan somatique (syndrome métabolique) et sur le plan des comorbidités psychiatriques (dont les comorbidités psychotraumatiques).
Dans cette étude prospective où 49 patients ont été inclus de façon aléatoire entre février et juillet 2013, nous avons évalué les éléments suivants : syndrome métabolique, MINI, THQ, IESR.
Cette population est âgée de 44 ans en moyenne. Le syndrome métabolique est retrouvé chez 33 % de la population. Les comorbidités psychiatriques : 75 % de dépression, 57 % de risque suicidaire moyen à élevé. Au niveau des évènements traumatisants (médiane du nombre d’évènements traumatisants à 6) : 45 % déclarent avoir subi des agressions sexuelles, 43 % des catastrophes naturelles. Le score total de l’IESR a un score médian à 37,5.
Ces résultats rappellent la nécessité de systématiser la recherche du syndrome métabolique et des évènements traumatiques en hospitalisation en psychiatrie.
Les femmes en attente de don d’ovocytes sont confrontées à diverses difficultés peu explorées dans la littérature : vécu subjectif douloureux, échecs des FIV précédentes, long délai d’attente d’un don, dissociation de la filiation génétique et gestationnelle… L’objectif principal est de déterminer si l’« attente d’un don d’ovocytes » est anxio-dépressiogène, et si le locus de contrôle externe constitue un facteur protecteur.
Les 3 groupes de femmes inclus sont en attente d’un don d’ovocytes (n = 10), en cours d’une première FIV (FIV1 ; n = 34) ou d’une deuxième FIV ou plus (FIV2+ ; n = 39). Elles ont été évaluées sur l’anxiété (State-Trait Anxiety Inventory), la dépression (Beck Depression Inventory), les locus de contrôle, la réaction à l’infertilité.
Les femmes receveuses étaient significativement plus âgées. Elles étaient significativement plus anxieuses mais pas plus dépressives que les groupes FIV. Leur anxiété actuelle était en partie expliquée par une internalité plus marquée. Pourtant, chez les femmes infertiles en général, c’est l’externalité de type « Autre toutpuissant » qui expliquait en partie la diminution de l’anxiété et la diminution du vécu négatif émotionnel de l’infertilité.
Ces résultats sur le locus de contrôle des femmes infertiles éclairent la réflexion sur le mode relationnel médecin malade, chez des patientes anxieuses sans maîtrise de leur fécondité et devant faire confiance aux équipes soignantes.
Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality. Differences between studies may occur as a result of different methodologies.
This work investigated the impact of using two different methods to measure depression and two different methods of analysis to establish relationships.
The work investigated the association between depression, CVD incidence (CVDI) and mortality from coronary heart disease (MCHD), smoking related conditions (MSRC), and all causes (MALL), in a major population study using depression measured from a validated scale and a depression measure derived by factor analysis, and analyses based on continuous data and grouped data.
Data from the PRIME Study (N=9,798 men) on depression and ten year CVD incidence and mortality were analysed using Cox proportional hazards models.
Using continuous data, no relationships with CVDI were found, but both measures of depression resulted in the emergence of positive associations between depression and mortality (MCHD, MSRC, MALL). Using grouped data, no associations with CVDI or MCVD were found, and associations between the measure derived from factor analysis and MSRC and MALL were also lost. Positive associations were only found between depression measured using validated items, MSRC and MALL.
These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the methodology used. Different findings based on methodology present clear problems for the determination of relationships. The differences here suggest the preferential use of validated scales and suggest against over-reduction via factor analysis and grouping.
Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.