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Supplemental material, sj-pdf-1-vmj-10.1177_1358863X231155305 for Management of spontaneous coronary artery dissection: Trends over time by Elliot Feldbaum, Elizabeth W Thompson, Tessa S Cook, Monika Sanghavi, Robert L Wilensky, Paul N Fiorilli and Jennifer Lewey in Vascular Medicine

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X231155305 for Management of spontaneous coronary artery dissection: Trends over time by Elliot Feldbaum, Elizabeth W Thompson, Tessa S Cook, Monika Sanghavi, Robert L Wilensky, Paul N Fiorilli and Jennifer Lewey in Vascular Medicine

Correctly identifying an individual's social context from passively worn sensors holds promise for delivering just-in-time adaptive interventions (JITAIs) to treat social anxiety disorder. In this study, we present results using passively collected data from a within-subject experiment that assessed physiological response across different social contexts (i.e, alone vs. with others), social phases (i.e., pre- and post-interaction vs. during an interaction), social interaction sizes (i.e., dyadic vs. group interactions), and levels of social threat (i.e., implicit vs. explicit social evaluation). Participants in the study ($N=46$) reported moderate to severe social anxiety symptoms as assessed by the Social Interaction Anxiety Scale ($\geq$34 out of 80). Univariate paired difference tests, multivariate random forest models, and follow-up cluster analyses were used to explore physiological response patterns across different social and non-social contexts. Our results suggest that social context is more reliably distinguishable than social phase, group size, or level of social threat, but that there is considerable variability in physiological response patterns even among these distinguishable contexts. Implications for real-world context detection and deployment of JITAIs are discussed.

Lattice parameters and elastic constants of pyrite-type FeOOH and AlOOH

We conducted an online study to examine the association of paranoia and safety behaviour use in a sample comprised of k = 142 UK adolescent-parent dyads (n = 284 participants) from the UK. We aim to investigate whether paranoia predicts safety behaviour use in adolescents and/or parents and whether adolescent paranoia and adolescent safety behaviour use are associated with parental paranoia.

The thesis examines the architectural features and measurements of the rock hewn tombs in the necropolis of El-Hawawish at Akhmim, the capital of the ninth province in Upper Egypt and a major administrative centre. The cemetery contains the burials of high and middle rank officials who administered the province in the Old Kingdom from the Fifth to the Eighth Dynasties (c. 2400-2160B.C.). The tombs are examined firstly, to determine whether architectural features could assist in the dating of their owners and secondly, whether certain features and measurements are indicative of the rank of these officials. -- Comparisons are made with tombs in the Memphite and provincial cemeteries and a study of the various elements of tomb architecture at El-Hawawish showed a chronological development similar to that observed in the tombs of the royal necropoli at Giza and Saqqara. Particular features which were introduced in certain reigns here can be found in what appear to be contemporary tombs at El-Hawawish and other provincial cemeteries. The rank of tomb owners is clearly revealed in the larger or smaller dimensions of chapels and burial chambers, and by the inclusion of certain features. Using the styles and features found occurring at a particular period, an estimate for dating large and obviously important, but uninscribed tombs, is also given.

The area chosen as the focus of the study was the Old Kingdom necropolis of El-Hawawish at Akhmim. This provincial cemetery was selected because of the large number of decorated tombs available for study within a single nome and the breadth of the dating span from the mid-Fifth to the Eighth Dynasties. -- The aim of this study was to closely examine the wall scenes in which the tomb owner was the principal focus, to identify the activities in which he chose to portray himself and to make a detailed analysis of the manner in which these activities were depicted. While the primary focus was the tombs at El-Hawawish, attention was also given to comparisons with other similarly dated provincial sites and with the capital, Memphis. Five principal occupations, or activities, of the tomb owner were scrutinised and similarities and differences noted. -- A number of specific questions, relating to the tomb owner's choice of his depictions were posed, such as the effect of the physical isolation of El-Hawawish from the capital, the impact of the status of the tomb owner and the importance of family relationships. Consideration was also given to the extent to which the tomb owners and/or the artists developed a distinct provincial style or incorporated features from tombs in other provinces or the capital. Finally, an attempt was made to identify specific aspects of the data which could provide reliable dating criteria. By this detailed observation, the thesis aimed to gain a greater understanding of the intention of the tomb owner in decorating his tomb and in presenting himself in his social milieu, particularly within his family setting and his province. -- As a result the study of the depictions of the tomb owner and the artistic style of his chosen themes and motifs has provided an understanding of the importance placed on the tomb owner's role and status in society. Comparative analysis of the interaction between the provinces and the capital indicated areas and periods where the traditional forms of the capital were preserved while still allowing the provincial tomb owners the opportunity for individual input. -- The stylistic study and analysis of the scenes was found to provide a useful method of cataloguing information and, through observing changes and developments, assist in suggesting appropriate dating criteria.

Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery.

This paper presents a classifier that takes airborne imagery acquired during marine megafauna surveys and classifies the glare intensity into four classes representing the severity of the glare. The objective of the classifier is to automate labour intensive and subjective components of the work performed by trained Marine Mammal Observers (MMOs). The proposed automatic method is based on a cascaded random forest architecture. The method uses features extracted from the histogram of the survey’s images and the metadata associated with respective images. The use of metadata is justified by the image formation model and we observed that it tends to improve the accuracy of the classifier. The proposed method provides results similar to that of trained MMOs. This is critical to the adoption of machine learning and machine vision technologies since introducing a change of methodology may impact the comparability of historic and future survey results when evaluating glare intensity., OCEANS 2021: San Diego – Porto, September 20-23, 2021,San Diego, CA, USA, Series: Ocean: Conference proceedings

This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.

Additional file 1. Fig. 1: Comparison of the cell density in (A) CD4+ cells (CD45+CD3+CD4+), (B) CD8+ cells (CD45+CD3+CD8+), (C) CD68+ cells, (D) CD163+ cells in pre- and post-treatment sections. NS, not significant, by unpaired t-test. Fig. 2: Multiplex immunohistochemistry staining for T-cell and macrophage markers on pre- and post-treatment biopsy sections, by survival. Upper panel (A-D) represents before-after plots for survival of less than 18 months. Comparison of the (A) cell density of CD4+ cells (CD45+CD3+CD4+), (B) CD8+ cells (CD45+CD3+CD8+), (C) CD68+ cells, (D) CD163+ cells in pre- and post-treatment biopsy sections. Lower panel (E–H) represents before-after plots for survival of greater than 18 months. Comparison of the (E) cell density of CD4+ cells (CD45+CD3+CD4+), (F) CD8+ cells (CD45+CD3+CD8+), (C) CD68+ cells, (F) CD163+ cells in pre- and post-treated biopsy sections. *P

Additional file 8. Review history.

Additional file 1: Figures S1-S13.

ObjectivesThere is a lack of evidence to inform the delivery and follow-up of bariatric surgery for people with severe obesity. The SurgiCal Obesity Treatment Study (SCOTS) is a national longitudinal cohort of people undergoing bariatric surgery. Here, we describe characteristics of the recruited SCOTS cohort, and the relationship between health and socioeconomic status with body mass index (BMI) and age.Participants/Methods445 participants scheduled for bariatric surgery at any of 14 centres in Scotland, UK, were recruited between 2013 and 2016 for this longitudinal cohort study (1 withdrawal); 249 completed health-related preoperative patient-reported outcome measures. Regression models were used to estimate the effect of a 10-unit increase in age or BMI, adjusting for sex, smoking and socioeconomic status.ResultsMean age was 46 years and median BMI was 47 kg/m2. For each 10 kg/m2 higher BMI, there was a change of −5.2 (95% CI −6.9 to –3.5; pConclusionsA higher BMI combined with older age is associated with poor physical functioning and quality of life in people seeking bariatric surgery treatment. Policy-makers must consider the health and care needs of these individuals and invest to provide increased access to effective weight management.Trial registration numberISRCTN47072588.

Figure S1. DNMT1 sequence variants identified in BWS patients. Figure S2. Sequence traces of DNMT1 variants generated by site-directed mutagenesis. Figure S3. Expression of GFP-tagged DNMT1 proteins in HeLa cells. Figure S4. Schematic of the trapping assay adapted from Frauer and Leonhardt (2009). (PPTX 1525Â kb)

Objective: To investigate the stability of four tension band wiring configurations alone without the contributions of K-wire stabilization. Study design: ex vivo experimentalSample population: Sixty-four tension band wiring constructsMethods: Four tension band configurations were applied to a metal trochanteric osteotomy model based on a canine femur: figure-of-eight with one twist (OT), figure-of-eight with two twists (TT), dual interlocking single loop (DISL), and double loop (DL). Configurations were mechanically tested under both monotonic loading (n = 8 per configuration) and incremental cyclic loading (n = 8 per configuration). Initial tension after tying, residual tension remaining after each cycle, and failure load at 2 mm of displacement (considered equivalent to clinical failure) were recorded. Results: The initial tension and the load to 2 mm of displacement was lower for OT wires compared to TT wires. The DL was the strongest and most stable configuration, generating greater initial tension, maintaining a greater percentage of residual tension under incremental cyclic loads, and resisting higher load before failure at 2 mm. Failure load was highly correlated with initial tension. Conclusion: This model enabled evaluation of tension band wire configuration independent of the fixation pin portion of the construct. Wire configurations that can be tightened to a greater tension during tying, like the DL, are better able to resist the tensile loads experienced by the construct. Clinical impact: In clinical situations where high tensile loads are expected, a tighter, more secure tension band wire configuration may be warranted.

Table S1. Methylation at non-11p15 imprinting centres in BWS cases with loss of methylation at KCNQ1OT1 TSS-DMR. Only samples with identified methylation changes are listed. Tables S2. aâ e Primers used for HRM of MTHFR, MTR, MTRR, MAT1A, CBS. Table S3. aâ e Primers used for sequencing MTHFR, MTR, MTRR, MAT1A, CBS. Table S4. aâ d. DNMT1 primers. Table S5 Pyrosequencing primers. (DOCX 226Â kb)

Osteopontin (OPN) protein levels in lungs from Stat1 +/+ and Stat1 −/− mice after one and 21 days of exposure to tMWCNTs or rMWCNTs. A) OPN protein in BALF after one and B) 21 days exposure to vehicle, tMWCNTs, or rMWCNTs as measured by ELISA. (*p

Evidence supports the use of brief psychosis-spectrum screeners for identifying individuals at an increased risk of developing a psychotic disorder. Research in this area, however, has focused on specialized settings, where individuals are often referred specifically for psychosis-spectrum symptoms, or in non-clinical settings where the utility of screening may be limited. Screening has not been well-studied in general mental health settings, such as college counseling centers, that serve young adults in the age range associated with highest risk for psychosis. This study investigated several approaches to psychosis-risk screening among help-seeking students at a university counseling center. The following screening methods were evaluated: 1) the PRIME Screen, a measure of psychosis-risk symptom severity, 2) the PRIME With Distress (PRIME-WD), a modified version of the PRIME with an embedded distress scale, and 3) a key-item approach that used scores from two psychosis-related questions within the Behavioral Health Measure-43 (BHM-43), a measure administered within the standard intake battery. Screening scores were compared to interview-based risk assessment to investigate the ability of each approach for identifying high-risk individuals. At intake, 510 students completed the PRIME and 26.7% screened positive. Overall, more PRIME symptomatology was associated with greater distress on all BHM-43 scales (e.g., general mental health, functioning, anxiety, and mood), with the exception of substance abuse. Psychosis-risk evaluations were completed with 44 participants. Participants categorized as high-risk upon clinical interview (n = 24) had greater functional impairment compared to the low-risk group (n = 20). Screening results indicated that PRIME scores identified high-risk individuals adequately, with some scoring methods (e.g., continuous rather than dichotomous scores) producing higher rates of accuracy (62.8-76.7%) for predicting risk status. Based on findings from this project, the PRIME may be a more accurate screen for psychosis-risk syndromes than BHM-43 key-items (76.7% versus 60.5% accuracy, respectively). This study demonstrated a need for psychosis-risk screening and assessment within a help-seeking college population. Overall, results suggest that assessing risk in a university counseling center is feasible and offers the promise of early identification to a much larger population relative to specialty clinics.

DSD gene variants in different global regions. DSD gene variants among the international cohort of 46,XY DSD patients. For ease of analysis, countries were grouped together into regions: Asia comprises Indonesia (97), Pakistan (25), Vietnam (35), Cambodia (16), India (1), a total of 174 patients ; Europe comprises the Netherlands (38), Austria (15), Belgium (6), and Italy (2), a total of 61 patients; and AUS & NZL comprises Australia (83) and New Zealand (7), a total of 90 patients. All curated variants are shown; those which have been curated and called pathogenic, likely pathogenic, and VUS. In the cohort from Asia, 35% of the patients were found to have a diagnostic variant (pathogenic or likely pathogenic), while this was 44% for Europe and 45% for AUS/NZL. Two patients from Canada were not included in the diagram. (PPTX 158 kb)

BackgroundFrontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.MethodsWe did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p

Interest in predicting psychosis-risk, and psychopathology associated with risk, has grown exponentially as research has suggested a link between early intervention for psychosis and better outcomes. Researchers have identified the clinical high-risk (CHR) state as a means of identifying vulnerable individuals potentially at risk for psychosis. Although youth at CHR tend to be in need of mental health services, there is a current lack of understanding regarding the distress specifically associated with this state. Investigating various methods of assessing psychosis-specific symptoms as well as other psychosocial difficulties experienced by CHR individuals might serve to guide clinicians in the identification and treatment of this population. Within a help-seeking sample of 81 youth aged 12-22, and a subsample of 56 youth-caregiver dyads, the current study examined the types of distress associated with psychosis-risk symptoms using the Behavior Assessment System for Children, Second Edition (BASC-2). Additionally, parent and youth reports of BASC-2 atypicality, a construct designed to capture symptoms similar to those associated with the psychosis-risk, were evaluated against clinician-rated risk symptoms. Results indicated that CHR symptoms are associated with a broad range of symptoms that warrant further investigation. Findings also suggested that BASC-2 atypicality (as reported by youth and parents) may be particularly useful for the assessment of CHR symptoms, as this construct appears to be predictive of clinician-rated risk. Given this evidence for convergent validity between atypicality and risk symptoms, as well as the additional clinical information the full measure affords, the BASC-2 may be a promising tool for psychosis-risk screening.

Labyrinth seal force estimates are important to the prediction of the stability of turbomachinery. The force prediction methods fall into several categories: experiments, bulk flow analysis, and finite volume analysis. Finite volume analysis can be split into two subcategories: self-developed and commercial. In this research, a commercial computational fluid dynamics (CFD) program called ANSYS-CFX was used to predict the forces generated in a labyrinth seal whirling at specified speeds. The results were compared to data from VT-FAST, a bulk flow code, and TASCflow, another commercial CFD program. It was shown that there were discrepancies among the results, and several hypotheses were made as to the reason for these discrepancies. Additionally, ANSYS-CFX was used to study the effect of labyrinth seal eccentricity ratio on the resultant force generated. It was shown that the radial force component within the seal behaved linearly with respect to eccentricity ratio. However, the tangential force component had no distinguishable relationship with the eccentricity ratio. It was hypothesized that the lack of a relationship was caused by the small fluctuations in the inlet swirl. Although the inlet swirl varied very little at each eccentricity ratio, it was shown there was a relationship between the tangential force and inlet swirl. Master of Science

The factors that regulate bioaccumulation of mercury in wetland systems and aquatic plants in particular have yet to be identified. Concentrations of total mercury were determined in water, sediments, and the yellow pond lily (Nuphar variegatum L.) for 22 wetlands from South-Central Ontario (Lat. 45$\sp\circ\ 11\sp\prime,$ Long. 78$\sp\circ\ 50\sp\prime$; Lat 46$\sp\circ\ 19\sp\prime$, Long. 80$\sp\circ\ 47\sp\prime)$ and for 23 wetlands from the St. Lawrence River (Lat. 45$\sp\circ\ 02\sp\prime,$ Long. 74$\sp\circ\ 44\sp\prime).$ The South-Central wetlands are remote from any industrial sources of mercury, whereas the wetlands from the St. Lawrence River come from an area where known Hg contamination exists. Positive correlations were found between the organic content of the sediments and the sediment Hg concentrations for both the South-Central and the St. Lawrence River wetlands. However, no relationships between water Hg and pH, alkalinity, and dissolved organic carbon (DOC) were found in either wetland group. The yellow pond lily is a common floating leaved aquatic plant which is the nutrient and energy source for a variety of wildlife. Thus, the importance of determining if the yellow pond lily accumulates toxic levels of mercury is evident. The results indicated that Nuphar variegatum does not accumulate mercury in relation to pH, alkalinity, DOC, or the organic content of the sediment, despite a wide range in these variables from the two wetland groups. Nuphar variegatum is an "excluder" or "non-indicator" of mercury. Remote South-Central wetlands had significantly higher concentrations of mercury in the sediments and the water compared to the St. Lawrence River wetlands. The South-Central wetlands also had significantly higher amounts of organic matter in the sediments and DOC in the water, both of which are known to bind mercury. (Abstract shortened by UMI.)

The Rusey Breccia, 80m long and 2-3m thick, occurs in the footwall of the Rusey Thrust, beneath the launch point of a series of thrust ramps. The thrust is a major Variscan structure exposed in the Boscastle shales on the north Cornish coast. The breccia forms a series of size graded layers, fining towards each layer boundary. The aligned clasts are surrounded in three dimensions by radial euhedral quartz. No fault gouge is present. The layering and re-brecciated clasts indicate repeated episodes of organisation and mineralisation. Clast organisation occurred in a dynamic environment resulting from episodic fluid injection associated with fault slip events, causing fluidisation of the clasts along the injection pathways. Mineralisation textures indicate relatively slow growth in a stable saturated medium capable of maintaining the clasts in suspension. Fluidisation is the dominant mechanism in the organisation of the breccia. Scale dependent differences in the behaviour of fluidised suspensions create the mineralising medium by forming a colloidal suspension of the fault gouge. The Rusey Breccia is compared with a similar breccia outcropping in Kimmeridge Bay, Dorset, formed in a thrust system developed at shallow depths in a carbonate system. The literature on Variscan and Comubian geology is reviewed and the structural geology of the Rusey Headland is described and explained as part of the Variscan orogenic system. Photoelastic modelling of the Rusey Thrust geometry is used to support the model proposed for the formation of the Rusey Breccia. The processes involved in the reorganisation and mineralisation of the breccia are described and reviewed. The internal structure and matrix morphology of the Rusey and Kimmeridge breccias is described and a statistical analysis of the Rusey data presented. The field, lab and analytical evidence presented in the thesis is synthesized to produce an evolutionary model for the Rusey Breccia. Imperial Users only

A female character type, one which is arguably unique to Canada, can be found in English-Canadian fiction from the time of the earliest creative writing, up to and including the present time. By virtue of her historical origins, this character type should be labelled the "pioneer woman" since her creation was, in fact, grounded in the actuality of the pioneer experience, and on details of that experience that were reconstructed and reinterpreted in fiction, often through a moralistic or idealistic filter.;In The Backwoods of Canada (1836) and The Canadian Settler's Guide (1855), Catharine Parr Traill described a pioneer woman's role on the Ontario frontier of the mid-nineteenth century, mingling fact with fancy to paint an idealized portrait of the Canadian pioneer woman. Traill's transposition of this figure into fiction, as for example, Catharine Maxwell of Canadian Crusoes (1852), resulted in her creation of what was, in effect, a new fictional character type: the pioneer woman.;Various versions of the pioneer woman appear in English-Canadian fiction throughout the hundred years following Traill's development of the character type. Sara Jeannette Duncan's The Imperialist (1904) and Ralph Connor's The Man From Glengarry (1901) and Glengarry School Days (1902) feature pioneer women who cope on a real physical frontier and also cope with a new type of frontier environment, one grounded in social and personal concerns rather than in the physical landscape. The longevity of the pioneer woman as character type in fiction is further demonstrated in the fiction of Margaret Laurence. Hagar Shipley of The Stone Angel (1964), Rachel Cameron of A Jest of God (1966), and Morag Gunn of The Diviners (1974) inhabit an internal, personal frontier. Like Duncan's Advena Murchison and Connor's Mrs. Murray, they are more contemporary versions of Traill's pioneer woman. All exhibit traits which link them to Traill's original model of the pioneer; all are part of a creative continuity which extends from Traill to Laurence and beyond.

Additional file 2: Appendix S1. Table and Text of Quantitative Drug Index adverse effects. Appendix S2. Figure and text documenting non-normal distribution of QDI scores. Appendix S3. Figure of randomization analysis and supporting text.

Platelet derived growth factor (PDGF) -A and -B expression in Stat1 +/+ and Stat1 −/− mouse lungs after exposure to tMWCNTs or rMWCNTs. A) Fold change in PDGF-A mRNA at one and B) 21 days post-exposure. C) Fold change in PDGF-B mRNA expression at one and D) 21 days post-exposure. Expression of mRNA normalized to B2M. (PDF 356 kb)

Additional file 2: Appendix S1. Table and Text of Quantitative Drug Index adverse effects. Appendix S2. Figure and text documenting non-normal distribution of QDI scores. Appendix S3. Figure of randomization analysis and supporting text.

Platelet derived growth factor (PDGF) -A and -B expression in Stat1 +/+ and Stat1 −/− mouse lungs after exposure to tMWCNTs or rMWCNTs. A) Fold change in PDGF-A mRNA at one and B) 21 days post-exposure. C) Fold change in PDGF-B mRNA expression at one and D) 21 days post-exposure. Expression of mRNA normalized to B2M. (PDF 356 kb)

Expression levels of collagen mRNAs determined via Taqman qRT-PCR of RNA isolated from mouse lungs 21Â days post-exposure. A) Fold change in Col1a1 and B) Col1a2 mRNA expression after 21Â days post-exposure. Expression of mRNA levels normalized to B2M. (PDF 137Â kb)

Soluble collagen content measured from mouse lungs 21Â days post-exposure. Average soluble collagen concentration per lung in each respective treatment after 21Â days of exposure to control, tMWCNTs, or rMWCNTs normalized to protein content of sample. (PDF 314Â kb)

Expression levels of collagen mRNAs determined via Taqman qRT-PCR of RNA isolated from mouse lungs 21Â days post-exposure. A) Fold change in Col1a1 and B) Col1a2 mRNA expression after 21Â days post-exposure. Expression of mRNA levels normalized to B2M. (PDF 137Â kb)

DSD gene variants in different global regions. DSD gene variants among the international cohort of 46,XY DSD patients. For ease of analysis, countries were grouped together into regions: Asia comprises Indonesia (97), Pakistan (25), Vietnam (35), Cambodia (16), India (1), a total of 174 patients ; Europe comprises the Netherlands (38), Austria (15), Belgium (6), and Italy (2), a total of 61 patients; and AUS & NZL comprises Australia (83) and New Zealand (7), a total of 90 patients. All curated variants are shown; those which have been curated and called pathogenic, likely pathogenic, and VUS. In the cohort from Asia, 35% of the patients were found to have a diagnostic variant (pathogenic or likely pathogenic), while this was 44% for Europe and 45% for AUS/NZL. Two patients from Canada were not included in the diagram. (PPTX 158 kb)

Interleukin-4 (IL-4) and IL-13 mRNA expression in Stat1 +/+ and Stat1 −/− mouse lungs after exposure to tMWCNTs or rMWCNTs. A) Fold change in IL-4 mRNA at one and B) 21 days post-exposure. C) Fold change in IL-13 mRNA expression at one and D) 21 days post-exposure. Expression of mRNA normalized to β2-microglobulin (B2M). (PDF 352 kb)

Physicochemical parameters of tangled (t) and rigid (r) multi-walled carbon nanotubes (MWCNTs). (PDF 31Â kb)

Interleukin-4 (IL-4) and IL-13 mRNA expression in Stat1 +/+ and Stat1 −/− mouse lungs after exposure to tMWCNTs or rMWCNTs. A) Fold change in IL-4 mRNA at one and B) 21 days post-exposure. C) Fold change in IL-13 mRNA expression at one and D) 21 days post-exposure. Expression of mRNA normalized to β2-microglobulin (B2M). (PDF 352 kb)

Soluble collagen content measured from mouse lungs 21Â days post-exposure. Average soluble collagen concentration per lung in each respective treatment after 21Â days of exposure to control, tMWCNTs, or rMWCNTs normalized to protein content of sample. (PDF 314Â kb)

Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.

International audience; To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ß11% of the cases (113 variants in 107/986 individuals: ß8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ß3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%–15% yield from array CGH alone.