Lymph node retrieval in pancreaticoduodenectomy specimens: does educating the pathologist matter?

AbstractBackgroundMany previous studies have suggested that the number of lymph nodes retrieved should serve as a benchmark for assessing the adequacy of the resection. The aim was to retrospectively observe the impact of nodal retrieval after educating the pathologist.MethodsPatients undergoing a pancreaticoduodenectomy (PD) between September 2005 and March 2009 were included in the study. The PDs performed between September 2005 and March 2008 were designated as Group A. The pathologists were educated regarding the importance of nodal counts in PD by the surgeon on the 1st April 2008. PDs performed between April 2008 and March 2009 were designated as Group B.ResultsNinety-eight PDs performed by a single surgeon (D.R.J.) for peri-ampullary malignancy were evaluated. The median number of lymph nodes retrieved in Group A was 11(3–32) nodes. The median number of lymph nodes retrieved in Group B was 22 (10–29) nodes (P < 0.001).The lymph node ratio (positive/total nodes), median number of positive nodes retrieved, and the node positivity (node positive compared to node negative) rate did not change.DiscussionA single intervention with the pathologists did impact the number of lymph nodes retrieved from PD specimens. However, the lymph node ratio and lymph node positivity rate remained unchanged. The pathologist is critical to nodal retrieval in PD, but the use of this lymph node number for benchmark of surgical adequacy may be simplistic

PDFTriage: Question Answering over Long, Structured Documents

Large Language Models (LLMs) have issues with document question answering (QA) in situations where the document is unable to fit in the small context length of an LLM. To overcome this issue, most existing works focus on retrieving the relevant context from the document, representing them as plain text. However, documents such as PDFs, web pages, and presentations are naturally structured with different pages, tables, sections, and so on. Representing such structured documents as plain text is incongruous with the user's mental model of these documents with rich structure. When a system has to query the document for context, this incongruity is brought to the fore, and seemingly trivial questions can trip up the QA system. To bridge this fundamental gap in handling structured documents, we propose an approach called PDFTriage that enables models to retrieve the context based on either structure or content. Our experiments demonstrate the effectiveness of the proposed PDFTriage-augmented models across several classes of questions where existing retrieval-augmented LLMs fail. To facilitate further research on this fundamental problem, we release our benchmark dataset consisting of 900+ human-generated questions over 80 structured documents from 10 different categories of question types for document QA

Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb blood pressure QTL region on rat chromosome 10

AbstractThe presence of blood pressure (BP) quantitative trait loci (QTL) on rat chromosome 10 has been clearly demonstrated by linkage analysis and substitution mapping. Using congenic strains containing the LEW rat chromosomal segments on the Dahl salt-sensitive (S) rat background, further iterations of congenic substrains were constructed and characterized to fine-map a chromosome 10 region (QTL1) linked to blood pressure. Comparison of seven congenic substrains refined QTL1 to a 1.17 Mb segment flanked by D10Mco88 and D10Mco89, which are located at 71,513,116 and 72,684,774 bp, respectively. The newly defined QTL1, containing 18 genes, is captured in its entirety within a single congenic substrain. A thorough transcript analysis revealed that 3 of these 18 genes, Ccl5, Ddx52, and RGD1559577, had nonsynonymous allelic variations between the S rat and the LEW rat. None of the detected transcripts within the newly defined QTL1 are implicated directly in BP control in humans or model organisms. Therefore, the present work defines a novel blood pressure QTL with three potential quantitative trait nucleotides

Expression of the Aeluropus littoralis AlSAP gene enhances rice yield under field drought at the reproductive stage

We evaluated the yields of Oryza sativa L. 'Nipponbare' rice lines expressing a gene encoding an A20/AN1 domain stress-associated protein, AlSAP, from the halophyte grass Aeluropus littoralis under the control of different promoters. Three independent field trials were conducted, with drought imposed at the reproductive stage. In all trials, the two transgenic lines, RN5 and RN6, consistently out-performed non-transgenic (NT) and wild-type (WT) controls, providing 50–90% increases in grain yield (GY). Enhancement of tillering and panicle fertility contributed to this improved GY under drought. In contrast with physiological records collected during previous greenhouse dry-down experiments, where drought was imposed at the early tillering stage, we did not observe significant differences in photosynthetic parameters, leaf water potential, or accumulation of antioxidants in flag leaves of AlSAP-lines subjected to drought at flowering. However, AlSAP expression alleviated leaf rolling and leaf drying induced by drought, resulting in increased accumulation of green biomass. Therefore, the observed enhanced performance of the AlSAP-lines subjected to drought at the reproductive stage can be tentatively ascribed to a primed status of the transgenic plants, resulting from a higher accumulation of biomass during vegetative growth, allowing reserve remobilization and maintenance of productive tillering and grain filling. Under irrigated conditions, the overall performance of AlSAP-lines was comparable with, or even significantly better than, the NT and WT controls. Thus, AlSAP expression inflicted no penalty on rice yields under optimal growth conditions. Our results support the use of AlSAP transgenics to reduce rice GY losses under drought conditions. (Résumé d'auteur

Influence of Spino-Pelvic and Postural Alignment Parameters on Gait Kinematics

Introduction: Postural alignment is altered with spine deformities that might occur with age. Alteration of spino-pelvic and postural alignment parameters are known to affect daily life activities such as gait. It is still unknown how spino-pelvic and postural alignment parameters are related to gait kinematics. Research question: To assess the relationships between spino-pelvic/postural alignment parameters and gait kinematics in asymptomatic adults. Methods: 134 asymptomatic subjects (aged 18-59 years) underwent 3D gait analysis, from which kinematics of the pelvis and lower limbs were extracted in the 3 planes. Subjects then underwent full-body biplanar X-rays, from which skeletal 3D reconstructions and spino-pelvic and postural alignment parameters were obtained such as sagittal vertical axis (SVA), center of auditory meatus to hip axis plumbline (CAM-HA), thoracic kyphosis (TK) and radiologic pelvic tilt (rPT). In order to assess the influence of spino-pelvic and postural alignment parameters on gait kinematics a univariate followed by a multivariate analysis were performed. Results: SVA was related to knee flexion during loading response (β = 0.268); CAM-HA to ROM pelvic obliquity (β = -0.19); rPT to mean pelvic tilt (β = -0.185) and ROM pelvic obliquity (β = -0.297); TK to ROM hip flexion/extension in stance (β = -0.17), mean foot progression in stance (β = -0.329), walking speed (β = -0.19), foot off (β = 0.223) and step length (β = -0.181). Significance: This study showed that increasing SVA, CAM-HA, TK and rPT, which is known to occur in adults with spinal deformities, could alter gait kinematics. Increases in these parameters, even in asymptomatic subjects, were related to a retroverted pelvis during gait, a reduced pelvic obliquity and hip flexion/extension mobility, an increased knee flexion during loading response as well as an increase in external foot progression angle. This was associated with a decrease in the walking pace: reduced speed, step length and longer stance phase

Mitochondrial polymorphisms in rat genetic models of hypertension

Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes

Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP

Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling B

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London