Prognostic value of desaturation during a six minute walk test in Idiopathic Interstitial Pneumonia

Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation.Weconclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.Supported in part by National Institutes of Health NHLBI Grant #P50HL46487, NHLBI, 1 K24 HL04212, and 1 K23 HL68713.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91972/1/2003 AJRCCM - Prognostic value of desaturation during a six minute walk test in Idiopathic Interstitial Pneumonia.pd

Integrating new sea‐level scenarios into coastal risk and adaptation assessments: An ongoing process

The release of new and updated sea‐level rise (SLR) information, such as from the Intergovernmental Panel on Climate Change (IPCC) Assessment Reports, needs to be better anticipated in coastal risk and adaptation assessments. This requires risk and adaptation assessments to be regularly reviewed and updated as needed, reflecting the new information but retaining useful information from earlier assessments. In this paper, updated guidance on the types of SLR information available is presented, including for sea‐level extremes. An intercomparison of the evolution of the headline projected ranges across all the IPCC reports show an increase from the fourth and fifth assessments to the most recent “Special Report on the Ocean and Cryosphere in a Changing Climate” assessment. IPCC reports have begun to highlight the importance of potential high‐end sea‐level response, mainly reflecting uncertainties in the Greenland/Antarctic ice sheet components, and how this might be considered in scenarios. The methods that are developed here are practical and consider coastal risk assessment, adaptation planning, and long‐term decision‐making to be an ongoing process and ensure that despite the large uncertainties, pragmatic adaptation decisions can be made. It is concluded that new sea‐level information should not be seen as an automatic reason for abandoning existing assessments, but as an opportunity to review (i) the assessment's robustness in the light of new science and (ii) the utility of proactive adaptation and planning strategies, especially over the more uncertain longer term

A Hypermorphic Missense Mutation in PLCG2, Encoding Phospholipase Cγ2, Causes a Dominantly Inherited Autoinflammatory Disease with Immunodeficiency

Whole-exome sequencing was performed in a family affected by dominantly inherited inflammatory disease characterized by recurrent blistering skin lesions, bronchiolitis, arthralgia, ocular inflammation, enterocolitis, absence of autoantibodies, and mild immunodeficiency. Exome data from three samples, including the affected father and daughter and unaffected mother, were filtered for the exclusion of reported variants, along with benign variants, as determined by PolyPhen-2. A total of eight transcripts were identified as possible candidate genes. We confirmed a variant, c.2120C>A (p.Ser707Tyr), within PLCG2 as the only de novo variant that was present in two affected family members and not present in four unaffected members. PLCG2 encodes phospholipase Cγ2 (PLCγ2), an enzyme with a critical regulatory role in various immune and inflammatory pathways. The p.Ser707Tyr substitution is located in an autoinhibitory SH2 domain that is crucial for PLCγ2 activation. Overexpression of the altered p.Ser707Tyr protein and ex vivo experiments using affected individuals’ leukocytes showed clearly enhanced PLCγ2 activity, suggesting increased intracellular signaling in the PLCγ2-mediated pathway. Recently, our laboratory identified in individuals with cold-induced urticaria and immune dysregulation PLCG2 exon-skipping mutations resulting in protein products with constitutive phospholipase activity but with reduced intracellular signaling at physiological temperatures. In contrast, the p.Ser707Tyr substitution in PLCγ2 causes a distinct inflammatory phenotype that is not provoked by cold temperatures and that has different end-organ involvement and increased intracellular signaling at physiological temperatures. Our results highlight the utility of exome-sequencing technology in finding causal mutations in nuclear families with dominantly inherited traits otherwise intractable by linkage analysis

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

The Vehicle, Fall 1983

Vol. 25, No. 1 Table of Contents Amish BoyDevon Flesorpage 3 SyllogismJ. Maura Davispage 3 Ten SecondsD.L. Lewispage 4 The Cedar ChestBridget M. Howepage 4 A Christmas With CarolSteve Longpage 5 TeethMichelle Mitchellpage 7 An I-Love-You PoemD.L. Lewispage 8 The Dragon SlayerSusan Gradypage 8 A DefinitionAmy J. Eadespage 9 FingernailsSuzanne Hornpage 10 The Liar\u27s TableBrook Wilsonpage 10 Fifi\u27s Last PartySteve Longpage 12 Absence/PresenceSuzanne Hornpage 13 From the Rantings of a Mad Astronomy StudentAmy J. Eadespage 13 In the Name of the Father, the Son, and MachiavelliF. Link Rapierpage 15 Errant LoverBecky Lawsonpage 16 DaddyKevin Lylespage 16 GhostsGary Ervinpage 17 TangoF. Link Rapierpage 17 Grandma\u27s SlippersBecky Lawsonpage 18 EdgesAmy J. Eadespage 19 Having ChildrenDevon Flesorpage 20 Young Black GirlKevin Lylespage 21 CatSuzanne Hornpage 22 Breakfast for OneMichelle Mitchellpage 22 A Modest ProposalBrooke Sanfordpage 23 Post MortemF. Link Rapierpage 26 Who Said I Forgot?Lynne Krausepage 27 The Corner Booth at StuckeysMaggie Kennedypage 28 The First DayDavis Brydenpage 29 DownLynne Krausepage 30 Fairie RingDevon Flesorpage 31 The LaundrymatKathy Fordpage 32 Sunday in OctoberBridget M. Howepage 32 The Kitchen WindowMaggie Kennedypage 33 UntitledChristina Maire Vitekpage 34 8th Grade Field Trip to SpringfieldMichelle Mitchellpage 34 Children of the FortiesF. Link Rapierpage 35 one winter and i was eightGary Ervinpage 35 Don\u27t we all know?Thomas B. Waltrippage 36 The TravelerMaggie Kennedypage 36 The VisitKathy Fordpage 40 CubismMaggie Kennedypage 40https://thekeep.eiu.edu/vehicle/1042/thumbnail.jp

The Vehicle, Fall 1983

Vol. 25, No. 1 Table of Contents Amish BoyDevon Flesorpage 3 SyllogismJ. Maura Davispage 3 Ten SecondsD.L. Lewispage 4 The Cedar ChestBridget M. Howepage 4 A Christmas With CarolSteve Longpage 5 TeethMichelle Mitchellpage 7 An I-Love-You PoemD.L. Lewispage 8 The Dragon SlayerSusan Gradypage 8 A DefinitionAmy J. Eadespage 9 FingernailsSuzanne Hornpage 10 The Liar\u27s TableBrook Wilsonpage 10 Fifi\u27s Last PartySteve Longpage 12 Absence/PresenceSuzanne Hornpage 13 From the Rantings of a Mad Astronomy StudentAmy J. Eadespage 13 In the Name of the Father, the Son, and MachiavelliF. Link Rapierpage 15 Errant LoverBecky Lawsonpage 16 DaddyKevin Lylespage 16 GhostsGary Ervinpage 17 TangoF. Link Rapierpage 17 Grandma\u27s SlippersBecky Lawsonpage 18 EdgesAmy J. Eadespage 19 Having ChildrenDevon Flesorpage 20 Young Black GirlKevin Lylespage 21 CatSuzanne Hornpage 22 Breakfast for OneMichelle Mitchellpage 22 A Modest ProposalBrooke Sanfordpage 23 Post MortemF. Link Rapierpage 26 Who Said I Forgot?Lynne Krausepage 27 The Corner Booth at StuckeysMaggie Kennedypage 28 The First DayDavis Brydenpage 29 DownLynne Krausepage 30 Fairie RingDevon Flesorpage 31 The LaundrymatKathy Fordpage 32 Sunday in OctoberBridget M. Howepage 32 The Kitchen WindowMaggie Kennedypage 33 UntitledChristina Maire Vitekpage 34 8th Grade Field Trip to SpringfieldMichelle Mitchellpage 34 Children of the FortiesF. Link Rapierpage 35 one winter and i was eightGary Ervinpage 35 Don\u27t we all know?Thomas B. Waltrippage 36 The TravelerMaggie Kennedypage 36 The VisitKathy Fordpage 40 CubismMaggie Kennedypage 40https://thekeep.eiu.edu/vehicle/1042/thumbnail.jp

Ribosomal RNA 2′O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

International audienceRecent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2′O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2′O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2′O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2′O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2′O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2′O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer

Adapting developing country epidemiological assessment techniques to improve the quality of health needs assessments in developed countries

BACKGROUND: We were commissioned to carry out three health assessments in urban areas of Dublin in Ireland. We required an epidemiologically robust method that could collect data rapidly and inexpensively. We were dealing with inadequate health information systems, weak planning data and a history of inadequate recipient involvement in health service planning. These problems had also been identified by researchers carrying out health assessments in developing countries. This paper reports our experience of adapting a cluster survey model originally developed by international organisations to assess community health needs and service coverage in developing countries and applying our adapted model to three urban areas in Dublin, Ireland METHODS: We adapted the model to control for socio-economic heterogeneity, to take account of the inadequate population list, to ensure a representative sample and to account for a higher prevalence of degenerative and chronic diseases. We employed formal as well as informal communication methods and adjusted data collection times to maximise participation. RESULTS: The model we adapted had the capacity to ascertain both health needs and health care delivery needs. The community participated throughout the process and members were trained and employed as data collectors. The assessments have been used by local health boards and non-governmental agencies to plan and deliver better or additional services. CONCLUSION: We were able to carry out high quality health needs assessments in urban areas by adapting and applying a developing country health assessment method. Issues arose relating to health needs assessment as part of the planning cycle and the role of participants in the process