Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Malaltia pulmonar intersticial; Fibrosi pulmonar; Pneumònia intersticial habitualEnfermedad pulmonar intersticial; Fibrosis pulmonar; Neumonía intersticial habitualInterstitial lung disease; Pulmonary fibrosis; Usual interstitial pneumoniaBackground Current interstitial lung disease (ILD) diagnostic guidelines assess criteria across clinical, radiologic and pathologic domains. Significant interobserver variation in histopathologic evaluation has previously been shown but the specific source of these discrepancies is poorly documented. We sought to document specific areas of difficulty and develop improved criteria that would reduce overall interobserver variation. Methods Using an internet-based approach, we reviewed selected images of specific diagnostic features of ILD histopathology and whole slide images of fibrotic ILD. After an initial round of review, we confirmed the presence of interobserver variation among our group. We then developed refined criteria and reviewed a second set of cases. Results The initial round reproduced the existing literature on interobserver variation in diagnosis of ILD. Cases which were pre-selected as inconsistent with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) were confirmed as such by multi-observer review. Cases which were thought to be in the spectrum of chronic fibrotic ILD for which UIP/IPF were in the differential showed marked variation in nearly all aspects of ILD evaluation including extent of inflammation and extent and pattern of fibrosis. A proposed set of more explicit criteria had only modest effects on this outcome. While we were only modestly successful in reducing interobserver variation, we did identify specific reasons that current histopathologic criteria of fibrotic ILD are not well defined in practice. Conclusions Any additional classification scheme must address interobserver variation in histopathologic diagnosis of fibrotic ILD order to remain clinically relevant. Improvements to tissue-based diagnostics may require substantial resources such as larger datasets or novel technologies to improve reproducibility. Benchmarks should be established for expected outcomes among clinically defined subgroups as a quality metric.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors

Benny Benson's Hidden Unangax̂ Heritage

This paper is dedicated to Alaska seventh grade students who know there is no chance of winning a contest. And enter anyway.Friday, July 9, 2027, will be the 100-year anniversary of the raising of the Alaska flag designed by seventh grade student Benny Benson. Top 8% of US state flag designs. Only US state flag designed by a Native American. Youngest designer. Indentured #217. Orphan. Poorest. “Inmate.” Only US state flag designer alive when the flags were flown to the Moon. As we prepare for the 100-year anniversary, what do know about Benny - as opposed to assume? We assumed that Benny was age 13 when he won the Alaska flag contest in 1927; history books said so. We assumed that his date of birth was October 12, 1913, and that his mother’s maiden name was Tatiana Schebolein. His official State of Alaska birth certificate said so. Yet, while researching Benny’s family tree, we uncovered documents which indicated otherwise. We contacted a relative who said Benny’s birth certificate is incorrect. We contacted the State of Alaska’s Health Analytics and Vital Records Section (HAVRS) who contacted the Alaska State Museums. A panel of Alaska history experts reviewed our documents and agreed that Benny’s birthdate should be corrected. HAVRS said we needed a court order. We petitioned the Alaska Superior Court, and on February 28, 2022, Alaska Superior Court Judge Adolf Zeman issued a court order (containing Unangam Tunuu – Aleut language) to correct Benny Benson’s birth records. Benny was actually born on September 12, 1912 – over 13 months earlier than previously reported. Benny’s mother’s maiden name was not Tatiana Schebolein; it was Tatiana Ioannovna Dediukhina. We also assumed that Benny was Alutiiq. Many sources said so, and good sources too: Museums, libraries, Alaska Native organizations, and Alaska historical societies. In 1950, when Benny was age 38, he moved to Kodiak. Sadly, in 1972, at age 59, Benny passed away and is buried in Kodiak. Kodiak is Alutiiq territory, and this may explain why Benny is often identified as Alutiiq. Yet Alaska Native ancestry is not defined solely upon where we move to later in life or the geographical location where we are born or are buried. Alaska Native ancestry is defined by where our ancestors are born and lived. When one of our genealogy colleagues casually mentioned finding records that indicated Benny’s mother Tatiana was born in Unangax̂ territory, this launched a lengthy-, in-depth genealogical investigation of his family tree. With help from many others, we found birth and marriage records which demonstrate that Benny’s mother Tatiana and his grandparents were born in Unalaska – the heart of Unangax̂ territory. Thus, Benny was a member of the Qawalangin Tribe of Unalaska – the Qawax̂ or Sea Lion Tribe. His great grandparents were from Amlia Village; Benny was a descendant of the Native Village of Atka. Despite others claiming without evidence that Benny Benson was Alutiiq, the documents found during this research show that Benny was Unangax̂. This research is significant on several fronts. First, it spotlights Benny Benson who – despite all odds – won a contest by reaching for the stars. Over 95 years after he won the Alaska flag contest, Benny is still in the news in a heartwarming story during the depth of a gloomy global pandemic and conflict in Ukraine. Like most family tree stories, there are sad (even heart-wrenching) times, but overall, Benny’s story is uplifting. This paper illuminates the plight of Alaska orphans who sometimes do not know their date of birth, the names of their ancestors, or their cultural heritage. Orphans need good families and thorough family tree research. This paper also underscores the importance of questioning written history and the need for history detectives keen on forensically investigating Alaska family trees with patient persistence while seeking the truth – whatever the truth may be. The birth record correction is significant because it changes Alaska history and represents a larger effort towards truth, reconciliation, equity, and racial justice for North American indigenous peoples who were often given the short shrift in the 20th Century. The birth record correction is a victory for archivists, Russian Orthodox family record keepers, and genealogists who love a complex mystery that twists and turns over time. This paper spotlights the need for careful research before centenary celebrations. Finally, this paper spotlights the linguistic and artistic talents of the Unangax̂ people from whom so much has been taken during the past 300 years and who have given so much including the name Alaska itself and now we know the strong design of the unique Alaska flag.Institute of Museum and Library Services basic grants # NG-01- 19-0037-19 and # NAB-246356-OLS-20

The Wide-field Infrared Survey Explorer (WISE): Mission Description and Initial On-orbit Performance

The all sky surveys done by the Palomar Observatory Schmidt, the European Southern Observatory Schmidt, and the United Kingdom Schmidt, the InfraRed Astronomical Satellite and the 2 Micron All Sky Survey have proven to be extremely useful tools for astronomy with value that lasts for decades. The Wide-field Infrared Survey Explorer is mapping the whole sky following its launch on 14 December 2009. WISE began surveying the sky on 14 Jan 2010 and completed its first full coverage of the sky on July 17. The survey will continue to cover the sky a second time until the cryogen is exhausted (anticipated in November 2010). WISE is achieving 5 sigma point source sensitivities better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic in bands centered at wavelengths of 3.4, 4.6, 12 and 22 microns. Sensitivity improves toward the ecliptic poles due to denser coverage and lower zodiacal background. The angular resolution is 6.1, 6.4, 6.5 and 12.0 arc-seconds at 3.4, 4.6, 12 and 22 microns, and the astrometric precision for high SNR sources is better than 0.15 arc-seconds.Comment: 22 pages with 19 included figures. Updated to better match the accepted version in the A

Bioenergy production and sustainable development: Science base for policymaking remains limited

The possibility of using bioenergy as a climate change mitigation measure has sparked a discussion of whether and how bioenergy production contributes to sustainable development. We undertook a systematic review of the scientific literature to illuminate this relationship and found a limited scientific basis for policymaking. Our results indicate that knowledge on the sustainable development impacts of bioenergy production is concentrated in a few well‐studied countries, focuses on environmental and economic impacts, and mostly relates to dedicated agricultural biomass plantations. The scope and methodological approaches in studies differ widely and only a small share of the studies sufficiently reports on context and/or baseline conditions, which makes it difficult to get a general understanding of the attribution of impacts. Nevertheless, we identified regional patterns of positive or negative impacts for all categories – environmental, economic, institutional, social and technological. In general, economic and technological impacts were more frequently reported as positive, while social and environmental impacts were more frequently reported as negative (with the exception of impacts on direct substitution of GHG emission from fossil fuel). More focused and transparent research is needed to validate these patterns and develop a strong science underpinning for establishing policies and governance agreements that prevent/mitigate negative and promote positive impacts from bioenergy production

Aging is associated with a prefrontal lateral-medial shift during picture-induced negative affect

The capacity to adaptively respond to negative emotion is in part dependent upon lateral areas of the prefrontal cortex (PFC). Lateral PFC areas are particularly susceptible to age-related atrophy, which affects executive function (EF). We used structural and functional magnetic resonance imaging (MRI) to test the hypothesis that older age is associated with greater medial PFC engagement during processing of negative information, and that this engagement is dependent upon the integrity of grey matter structure in lateral PFC as well as EF. Participants (n = 64, 38–79 years) viewed negative and neutral scenes while in the scanner, and completed cognitive tests as part of a larger study. Grey matter probability (GMP) was computed to index grey matter integrity. FMRI data demonstrated less activity in the left ventrolateral PFC (VLPFC) and greater ventromedial PFC (VMPFC) activity with increasing age during negative-picture viewing. Age did not correlate with amygdala responding. GMP in VLPFC and EF were negatively associated with VMPFC activity. We conclude that this change from lateral to medial PFC engagement in response to picture-induced negative affect reflects decreased reliance on executive function-related processes, possibly associated with reduced grey matter in lateral PFC, with advancing age to maintain emotional functioning

Social Relationships and Mortality Risk: A Meta-analytic Review

In a meta-analysis, Julianne Holt-Lunstad and colleagues find that individuals' social relationships have as much influence on mortality risk as other well-established risk factors for mortality, such as smoking

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe