Secondary hypertrophic osteoarthropathy an unusual cause of arthritis in childhood

Although an uncommon occurrence in childhood, hypertrophic osteoarthropathy secondary to tumors—most commonly to osteogenic sarcoma with pulmonary metastasis—may cause severe joint pain and swelling. The syndrome should be considered in the differential diagnosis of acute arthritis in childhood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37729/1/1780190511_ftp.pd

Language impairments in the development of sign: Do they reside in a specific modality or are they modality-independent deficits?

Various theories of developmental language impairments have sought to explain these impairments in modality-specific ways – for example, that the language deficits in SLI or Down syndrome arise from impairments in auditory processing. Studies of signers with language impairments, especially those who are bilingual in a spoken language as well as a sign language, provide a unique opportunity to contrast abilities across language in two modalities (cross-modal bilingualism). The aim of the article is to examine what developmental sign language impairments can tell us about the relationship between language impairments and modality. A series of individual and small group studies are presented here illustrating language impairments in sign language users and cross-modal bilinguals, comprising Landau-Kleffner syndrome, Williams syndrome, Down syndrome, Autism and SLI. We conclude by suggesting how studies of sign language impairments can assist researchers to explore how different language impairments originate from different parts of the cognitive, linguistic and perceptual systems

Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.

It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes, TRIP10 and KDM3A, were identified. The aGEw test is implemented in an R package aGE.We thank the two anonymous reviewers for their constructive comments. This research was supported by the National Institutes of Health (NIH) grant R01CA169122; P.W. was supported by NIH grants R01HL116720 and R21HL126032. S.H.O. was supported by NIH grant P30CA008748. R.E.N. and the Queensland Pancreatic Cancer Study were funded by the Australian National Health and Medical Research Council. The authors thank Ms. Jessica Swann and the National Institute of Statistical Sciences writing workshop for editorial assistance and suggestions. The authors acknowledge the Texas Advanced Computing Center at The University of Texas at Austin for providing computing resources. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated. The authors declare that there is no conflict of interest

WACCM simulations: Decadal winter-to-spring climate impact on middle atmosphere and troposphere from medium energy electron precipitation

Energetic particle precipitation is one of the main processes by which the sun influences atmospheric composition and structure. The polar middle atmosphere is chemically disturbed by the precipitation-induced production of nitric oxides (NOx) and hydrogen oxides (HOx) and the associated ozone (O3) loss, but the importance for the dynamics is still debated. The role of precipitating medium energy electrons (MEEs), which are able to penetrate into the mesosphere, has received increased attention, but has only recently begun to be incorporated in chemistry-climate models. We use the NCAR Whole Atmosphere Community Climate Model (WACCM) to study the climate impact from MEE precipitation by performing two idealized ensemble experiments under pre-industrial conditions, with and without the MEE forcing, over the period of the solar cycle 23 (only full calendar years, 1997–2007). Each experiment includes 20 11-year ensemble members, total 220 years. Our results indicate a strong month-to-month variability in the dynamical response to MEE throughout the winter period. We find a strengthening of the polar vortex in the northern hemisphere during December, but the signal decays rapidly in the following months. The polar vortex strengthening is likely attributable to planetary wave reduction due to increased zonal symmetries in upper stratospheric ozone heating, initially triggered by MEE-induced NOx advected into the sunlit regions. We also find a similar early winter polar vortex strengthening in the southern hemisphere during June. Changes in mean meridional circulation accompany these anomalous wave forcings, leading to dynamically-induced vertical temperature dipoles at high latitudes. The associated weakening of the stratospheric mean meridional circulation results in an upper stratospheric polar ozone deficit in early winter. This polar cap ozone deficit is strongest in the southern hemisphere and contributes to a polar vortex weakening in late winter, in concert with increased planetary wave forcing. In both hemispheres, the stratospheric polar vortex signal seems to migrate downwards into the troposphere and to the surface

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

Memorable tourism experiences and their consequences : An interaction ritual (IR) theory approach

Tourism experiences, memories thereof, and their consequences tend to be analysed separately, often focusing on the individual’s perspective. This paper introduces Collins’ (2004) interaction ritual (IR) theory to develop a micro-sociological interpretation of these phenomena as interconnected elements of IR chains. A longitudinal qualitative study of a multi-cultural festival held in Italy, the Mondiali Antirazzisti (Anti-racist World Cup), is used to show how emotional experiences and patterns of collective action are reproduced by the returning attendees in their home communities through the trans-local appropriation of the event’s format. Findings lead to a revised model of IR chains to explain the trans-local dimension of transformational event tourism. The implications for wider application of IR theory within tourism are discussed

Twenty-three unsolved problems in hydrology (UPH) – a community perspective

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through on-line media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focussed on process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come