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The order Diptera (true flies) holds promise as a model taxon in evolutionary developmental biology due to the inclusion of the model organism, Drosophila melanogaster , and the ability to cost-effectively rear many species in laboratories. One of them, the scuttle fly Megaselia abdita (Phoridae) has been used in evolutionary developmental biology for 30 years and is an excellent phylogenetic intermediate between fruit flies and mosquitoes but remains underdeveloped in genomic resources. Here, we present a de novo chromosome-level assembly and annotation of M. abdita and transcriptomes of 9 embryonic and 4 postembryonic stages. We also compare 9 stage-matched embryonic transcriptomes between M. abdita and D. melanogaster . Our analysis of these resources reveals extensive chromosomal synteny with D. melanogaster , 28 orphan genes with embryo-specific expression including a novel F-box LRR gene in M. abdita , and conserved and diverged features of gene expression dynamics between M. abdita and D. melanogaster . Collectively, our results provide a new reference for studying the diversification of developmental processes in flies., Competing Interests: Competing interests The authors declare no competing interests.

Establishing the anterior-posterior body axis is a fundamental process during embryogenesis, and the fruit fly, Drosophila melanogaster , provides one of the best-known case studies of this process. In Drosophila, localized mRNA of bicoid serves as anterior determinant (AD). Bicoid engages in a concentration-dependent competition with nucleosomes and initiates symmetry-breaking along the AP axis by promoting chromatin accessibility at the loci of transcription factor (TF) genes that are expressed in the anterior of the embryo. However, ADs of other fly species are unrelated and structurally distinct, and little is known about how they function. We addressed this question in the moth fly, Clogmia albipunctata , in which a maternally expressed transcript isoform of the pair-rule segmentation gene odd-paired is localized in the anterior egg and has been co-opted as AD. We provide a de novo assembly and annotation of the Clogmia genome and describe how knockdown of zelda and maternal odd-paired transcript affect chromatin accessibility and expression of TF-encoding loci. The results of these experiments suggest direct roles of Cal-Zld in opening and closing chromatin during nuclear cleavage cycles and show that Clogmia's maternal odd-paired activity promotes chromatin accessibility and anterior expression during the early phase of zygotic genome activation at Clogmia's homeobrain and sloppy-paired loci. We conclude that unrelated dipteran ADs initiate anterior-posterior axis-specification at the level of enhancer accessibility and that homeobrain and sloppy-paired homologs may serve a more widely conserved role in the initiation of anterior pattern formation given their early anterior expression and function in head development in other insects., Competing Interests: Competing interests The authors declare no competing interests.

Background: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO., Methods: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503)., Findings: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%])., Interpretation: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO., Funding: Regeneron Pharmaceuticals and Bayer., Competing Interests: Declaration of interests DMB serves as a scientific adviser for Regeneron/Bayer and Genentech/Roche and as a member of the Regeneron Combination Products Steering Committee. DSB has served as a consultant for Adverum, Allergan, Bayer, Genentech, Graybug, Novartis, Regeneron Pharmaceuticals, REGENXBIO, and Roche. DVD is a consultant to Allergan, AsclepiX, Boehringer Ingelheim, Clearside, Genentech, Kodiak Sciences, and Regeneron Pharmaceuticals and has received research funding from AsclepiX, Boehringer Ingelheim, Genentech, and Regeneron Pharmaceuticals. CCW is a consultant for 4DMT, AbbVie, Adverum, Aerie, AGTC, Alcon, Annexon, Apellis, Arrowhead, Bausch + Lomb, Boehringer Ingelheim, Cholgene, Clearside, Curacle, EyePoint, Genentech, Gyroscope, IACTA, Iveric Bio, Janssen, Kato, Kiora, Kodiak Sciences, Kriya, Merck, Nanoscope, NGM, Novartis, Ocular Therapeutix, OcuTerra, ONL, Opthea, Oxular, Palatin, PerceiveBio, Perfuse, Ray, RecensMedical, Regeneron Pharmaceuticals, REGENXBIO, Roche, and Stealth and has received research support from 4DMT, Adverum, AffaMed, Alexion, Alimera, Alkahest, Allgenesis, Amgen, Annexin, Annexon, Apellis, AsclepiX, Bayer, Boehringer Ingelheim, Clearside, Curacle, EyePoint, Gemini, Genentech, GlaxoSmithKline, Gyroscope, IONIS, iRENIX, Iveric Bio, Kodiak Sciences, LMRI, Nanoscope, Neurotech, NGM, Novartis, Ocular Therapeutix, Ocuphire, OcuTerra, Opthea, Ophthotech, Oxurion, Oxular, Oyster Point, PerceiveBio, Regeneron Pharmaceuticals, REGENXBIO, Roche, and UNITY. TSa is a consultant for Bayer, Boehringer Ingelheim, Chugai/Roche, Novartis, and Senju. ASe is a consultant for Syneos Health and Novartis; has served as an adviser for Roche; and has contributed to the industry-sponsored international multicentre studies for Allergan, Amgen, Bayer, Formycon, Hexal, Iveric Bio, Kodiak Sciences, Oculis, Opthea, Novartis, Qilu Pharma, Regeneron Pharmaceuticals, Roche, and Sam Chun Dang Pharma. AJB, RV, KWC, KR, RR, YC, WS, DV, RB, and BH are employees and stockholders of Regeneron Pharmaceuticals. SL, US-O, TSc, ASc, and XZ are employees of Bayer. GDY is the founding scientist, President, and Chief Scientific Officer of Regeneron Pharmaceuticals. SS is an adviser and contributes to the industry-sponsored international multicentre studies for AbbVie, Bayer, Boehringer Ingelheim, Novartis, Optos, and Roche and has received consultancy fees from Allergan, Apellis, Bayer, Biogen, Boehringer Ingelheim, Eyebiotech, Novartis Pharma, Optos, and Roche. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg., Methods: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing., Findings: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%])., Interpretation: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD., Funding: Bayer AG and Regeneron Pharmaceuticals., Competing Interests: Declaration of interests PL is a consultant for Aerie, Allergan, Apellis, Bausch + Lomb, Bayer, Biogen, Boehringer Ingelheim, I-Care, Genentech, Novartis, Ocular Therapeutix, Outlook Therapeutics, and Roche. J-FK receives consulting fees from AbbVie, Apellis, Bayer, Janssen, Nano Retina, Roche, Théa Pharmaceuticals, and Carl Zeiss Meditec; and is a member of data and safety monitoring boards or advisory boards for Alexion, Novo Nordisk, and Oxular. JSH receives consulting fees for 4D Molecular Therapeutics, Abpro, Adverum, AffaMed Therapeutics, Applied Genetics Technologies Corporation, Akouos, Allegro, Annexon, Apellis, AsclepiX Therapeutics, Bausch + Lomb, Biovisics, Clearside, Curacle, DTx Pharma, Exegenesis, Roche and Genentech, Glaukos, Gyroscope Therapeutics, ImmunoGen, Iveric Bio, Janssen R&D, jCyte, Kriya, Nanoscope, NGM Bio, Notal Vision, Novartis, Ocular Therapeutix, Ocuphire, OcuTerra, OliX, ONL Therapeutics, Outlook Therapeutics, Palatin Technologies, Perceive Biotherapeutics, Ray Therapeutics, Regeneron Pharmaceuticals, REGENXBIO, RetinAI, RevOpsis Therapeutics, Stealth BioTherapeutics, Théa Pharmaceuticals, and Vanotech; receives grants or contracts for 4D Molecular Technologies, Annexon, Apellis, AsclepiX Therapeutics, Ashvattha, Bayer, Cognition Therapeutics, Curacle, Roche and Genentech, Gyroscope Therapeutics, Iveric Bio, Janssen R&D, Kodiak, NGM, Notal Vision, Novartis, OcuTerra, Perceive Bio, Regeneron Pharmaceuticals, and REGENXBIO; has equity in Adverum, Aldeyra Therapeutics, Allegro, Aviceda, DTx Pharma, jCyte, Ocuphire, Ocular Therapeutix, RevOpsis Therapeutics, Vinci Pharmaceuticals, and Vitranu; and is on the Board of Directors for Ocular Therapeutix. FGH has served as a consultant for Acucela, Apellis, Bayer, Boehringer Ingelheim, Bioeq/Formycon, Roche and Genentech, Graybug Vision, IvericBio, Lin BioScience, Novartis, and Stealth BioTherapeutics; has received research support from Acucela, Apellis, Bayer, Bioeq/Formycon, and Roche and Genentech; has received honoraria from Bayer, Ellex, Roche and Genentech, Graybug Vision, Lin BioScience, Novartis, Oxurion, and Stealth BioTherapeutics; has received support for attending meetings or travel from Bayer, Roche and Genentech, Heidelberg Engineering, Lin BioScience, Novartis, and Stealth BioTherapeutics; has been a member of EURETINA and the German Ophthalmology Society (DOG); has other financial or non-financial interests in Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, CenterVue, Ellex, Roche and Genentech, Geuder, Heidelberg Engineering, IvericBio, Chengdu Kanghong Pharmaceuticals, NightStarX, Novartis, Optos, Pixium Vision, and Zeiss. WLC serves as a consultant for Genentech and Regeneron Pharmaceuticals; has received research support from Genentech; is a lecturer for Bayer, Genentech, and Regeneron Pharmaceuticals; and has received travel support from Bayer, Genentech, and Regeneron Pharmaceuticals. TYW receives consulting fees from Aldropika Therapeutics, Bayer, Boehringer Ingelheim, Genetech, Iveric Bio, Novartis, Oxurion, Plano, Roche, Sanofi, and Shanghai Henlius; and holds patents and is the co-founder of EyRiS and Visre. DE is a speaker for Allergan, Apellis, Bausch + Lomb, Bayer, the Dutch Ophthalmic Research Center, EyePoint, Genentech, and Novartis; is a consultant for Alimera Sciences, Allergan, Apellis, Bausch + Lomb, Coherus, Crinetics, DORC, EyePoint, Genentech, Gyroscope Therapeutics, Iveric Bio, KKR, Kodiak, Novartis, Ocular Therapeutix, Opthea, Outlook Therapeutics, RecensMedical, Regeneron Pharmaceuticals, REGENXBIO, Revive Pharmaceuticals, USRetina, and Vial; is an investigator for 4D Molecular Therapeutics, Alexion, Alkahest, Allgenesis, Annexon, AsclepiX Therapeutics, Bayer, Chengdu Kanghong Biotech (PANDA Trial stopped April, 2021), EyePoint, Gemini Therapeutics, Genentech, Gyroscope Therapeutics, Ionis, Iveric Bio, Kodiak, Mylan, NGM Bio, Novartis, Ocular Therapeutix, Opthea, RecensMedical, Regeneron Pharmaceuticals, REGENXBIO, and UNITY Biotechnology; is a stockholder for or has equity in Boston Image Reading Center, Clearside Biomedical, Hemera Biosciences, Network Eye, Revive Pharmaceuticals, and USRetina; and is a founder of Network Eye. TI has received financial support from NIDEK, Topcon Healthcare, Santen Pharmaceutical, Novartis, Senju Pharmaceutical, Alcon Japan, HOYA Vision Care, and AMO Pharma; has received consultancy fees from Bayer Yakuhin, Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Janssen Pharmaceutical, Novartis Pharma, Senju Pharmaceutical, and Kyowa Kirin; has received lecture fees from Bayer Yakuhin, Novartis, Alcon Japan, Santen Pharmaceuticals, Senju Pharmaceutical, Topcon Healthcare, Chugai Pharmaceutical, Canon, NIDEK, Otsuka Pharmaceutical, and Nikon; has a patent with Topcon; and has received rewards from Kyowa Kirin. SX has received consulting fees from Alcon, Allergan, Bayer, Innovent Biologics, Chengdu Kanghong Biotech, Novartis, Roche, and Carl Zeiss Meditec. US-O and TS are employees and stockholders of Bayer. SL, AS, and XZ are employees of Bayer. AJB, RV, KWC, KR, RR, YC, WS, RB, and BH are employees and stockholders of Regeneron Pharmaceuticals. GDY is the Founding Scientist, President, and Chief Scientific Officer of Regeneron Pharmaceuticals., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Lyme disease is the most common vectorborne disease in the Northern hemisphere with more than 400 000 new cases in the USA annually. Lyme meningitis is an uncommon but potentially serious clinical manifestation of Lyme disease. Intravenous ceftriaxone had been the first-line treatment for Lyme meningitis, but is associated with a high rate of complications. Although efficacy and effectiveness (or real-world evidence) data for oral doxycycline are limited, practice guidelines were recently expanded to recommend either oral doxycycline or ceftriaxone as first-line treatments for Lyme meningitis. Our goal is to compare oral doxycycline with intravenous ceftriaxone for the treatment of Lyme meningitis on short-term recovery and long-term quality of life., Methods and Analysis: We are performing a prospective cohort study at 20 US paediatric centres located in diverse geographical range where Lyme disease is endemic. The clinical care team will make all antibiotic treatment decisions for children with Lyme meningitis, as per usual practice. We will follow enrolled children for 6 months to determine time of acute symptom recovery and impact on quality of life., Ethics and Dissemination: Boston Children's Hospital, the single Institutional Review Board (sIRB), has approved the study protocol with the other 19 enrolling sites as well as the Utah data coordinating centre relying on the Boston Children's Hospital sIRB. Once the study is completed, we will publish our findings in a peer-reviewed medical journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the reported rates of intraocular inflammation (IOI) in patients treated with intravitreal aflibercept (IVT-AFL) 2 mg in routine clinical practice (ie, outside interventional studies), across all indications and within all countries (excluding the United States), with access to either the vial presentation or pre-filled syringe (PFS)., Patients and Methods: A search was conducted using the Bayer EYLEA ® Global Safety Pharmacovigilance Database for reported cases of IOI and IVT-AFL use between October 2012 and March 31, 2022., Results: With more than 10 years of post-marketing experience with the IVT-AFL vial presentation (>25 million sold units), and over 2 years of experience with the PFS of IVT-AFL (>6.7 million sold units) the rate of any IOI, including endophthalmitis, outside the United States was 0.3 events per 10,000 units for the PFS and 1.2 events per 10,000 units for the vial presentation. The event rates specifically for endophthalmitis were 0.1 per 10,000 units for the IVT-AFL PFS and 0.6 per 10,000 units for the IVT-AFL vial presentation., Conclusion: In patients with retinal diseases treated in routine clinical practice with IVT-AFL either from a vial or the PFS, medically important adverse events of IOI, and in particular, endophthalmitis, are infrequently reported events. Numerically, reported rates of IOI and endophthalmitis are low for the vial presentation and even lower for the PFS., Competing Interests: All authors are salaried employees of, and hold stock options or own stock in, Bayer companies. The authors report no other conflicts of interest in this work., (© 2023 Schmidt-Ott et al.)

The C2H2 zinc finger gene cucoid establishes anterior-posterior (AP) polarity in the early embryo of culicine mosquitoes. This gene is unrelated to genes that establish embryo polarity in other fly species (Diptera), such as the homeobox gene bicoid, which serves this function in the traditional model organism Drosophila melanogaster. The cucoid gene is a conserved single copy gene across lower dipterans but nothing is known about its function in other species, and its evolution in higher dipterans, including Drosophila, is unresolved. We found that cucoid is a member of the ZAD-containing C2H2 zinc finger (ZAD-ZNF) gene family and is orthologous to 27 of the 91 members of this family in D. melanogaster, including M1BP, ranshi, ouib, nom, zaf1, odj, Nnk, trem, Zif, and eighteen uncharacterized genes. Available knowledge of the functions of cucoid orthologs in Drosophila melanogaster suggest that the progenitor of this lineage specific expansion may have played a role in regulating chromatin. We also describe many aspects of the gene duplication history of cucoid in the brachyceran lineage of D. melanogaster, thereby providing a framework for predicting potential redundancies among these genes in D. melanogaster., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The conservation of gene networks that specify and differentiate distinct tissues has long been a subject of great interest to evolutionary developmental biologists, but the question of how pre-existing tissue-specific developmental trajectories merge is rarely asked. During the radiation of flies, two extraembryonic epithelia, known as serosa and amnion, evolved into one, called amnioserosa. This unique extraembryonic epithelium is found in fly species of the group Schizophora, including the genetic model organism Drosophila melanogaster , and has been studied in depth. Close relatives of this group develop a serosa and a rudimentary amnion. The scuttle fly Megaselia abdita has emerged as an excellent model organism to study this extraembryonic tissue organization. In this review, development and functions of the extraembryonic tissue complements of Drosophila and Megaselia are compared. It is concluded that the amnioserosa combines cells, genetic pathway components and functions that were previously associated either with serosa development or amnion development. The composite developmental trajectory of the amnioserosa raises the question of whether merging tissue-specific gene networks is a common evolutionary process. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.

Background: The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson's disease (PwP), a status quo analysis of current care practice is required., Objective: To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019?, Material and Methods: The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder., Results: Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4‑fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson's disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist., Discussion: The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care., (© 2022. The Author(s).)

Mechanisms and evolution of primary axis specification in insects are discussed in the context of the roles of ß-catenin and TCF in polarizing metazoan embryos. Three hypotheses are presented. First, insects with sequential segmentation and posterior growth use cell-autonomous mechanisms for establishing embryo polarity via the nuclear ratio of ß-catenin and TCF. Second, TCF homologs establish competence for anterior specification. Third, the evolution of simultaneous segmentation mechanisms, also known as long-germ development, resulted in primary axis specification mechanisms that are independent of ß-catenin but reliant on TCF, a condition that preceded the frequent replacement of anterior determinants in long germ insects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Commercial motor vehicle drivers, such as truck drivers, experience unique health, lifestyle, and occupational challenges directly associated with their profession., Methods: All participants in this multistate cross-sectional study completed questionnaire measurements. Participants were categorized with metabolic syndrome (MetS) if they had at least three of the five modified criteria used in the joint scientific statement on metabolic syndrome., Results: Overall MetS prevalence was 52.4% (n = 428) of the 817 participants. Prevalence of MetS criteria were waist circumference (n = 634, 77.0%), low HDL cholesterol (n = 580, 71.0%), elevated triglycerides (n = 552, 67.6%), elevated blood pressure (n = 175, 21.2%), and elevated hemoglobin A1c (n = 97, 11.9%). Truck drivers were 2.7 times more likely to have MetS compared to the general working population., Conclusion: Truck drivers in the United States have a high prevalence of MetS compared to the general working population.

The abundance and distribution of water within Mars through time plays a fundamental role in constraining its geological evolution and habitability. The isotopic composition of martian hydrogen provides insights into the interplay between different water reservoirs on Mars. However, D/H (deuterium/hydrogen) ratios of martian rocks and of the martian atmosphere span a wide range of values. This has complicated identification of distinct water reservoirs in and on Mars within the confines of existing models that assume an isotopically homogenous mantle. Here we present D/H data collected by secondary ion mass spectrometry for two martian meteorites. These data indicate that the martian crust has been characterized by a constant D/H ratio over the last 3.9 billion years. The crust represents a reservoir with a D/H ratio that is intermediate between at least two isotopically distinct primordial water reservoirs within the martian mantle, sampled by partial melts from geochemically depleted and enriched mantle sources. From mixing calculations, we find that a subset of depleted martian basalts are consistent with isotopically light hydrogen (low D/H) in their mantle source, whereas enriched shergottites sampled a mantle source containing heavy hydrogen (high D/H). We propose that the martian mantle is chemically heterogeneous with multiple water reservoirs, indicating poor mixing within the mantle after accretion, differentiation, and its subsequent thermochemical evolution., Competing Interests: Financial/Non-financial Competing Interests We declare no financial or non-financial competing interests related to this work.

Unrelated genes establish head-to-tail polarity in embryos of different fly species, raising the question of how they evolve this function. We show that in moth flies ( Clogmia , Lutzomyia ), a maternal transcript isoform of odd-paired (Zic) is localized in the anterior egg and adopted the role of anterior determinant without essential protein change. Additionally, Clogmia lost maternal germ plasm, which contributes to embryo polarity in fruit flies ( Drosophila ). In culicine ( Culex , Aedes) and anopheline mosquitoes (Anopheles), embryo polarity rests on a previously unnamed zinc finger gene ( cucoid ), or pangolin ( dTcf ), respectively. These genes also localize an alternative transcript isoform at the anterior egg pole. Basal-branching crane flies ( Nephrotoma ) also enrich maternal pangolin transcript at the anterior egg pole, suggesting that pangolin functioned as ancestral axis determinant in flies. In conclusion, flies evolved an unexpected diversity of anterior determinants, and alternative transcript isoforms with distinct expression can adopt fundamentally distinct developmental roles., Competing Interests: YY, JK, IM, FC, EC, JR, US No competing interests declared, (© 2019, Yoon et al.)

Objective: To quantify sensitivity and specificity of the tender points and demonstrate how variability in case definition impacts prevalence of lateral epicondylitis (LE)., Methods: Baseline data analyzed from 1216 workers from the WISTAH study, a multicenter prospective cohort study of upper extremity musculoskeletal disorders. All workers completed computerized questionnaires, structured interviews, and two independent physical examinations in accordance with an established protocol., Results: The prevalence of LE differed based on case definition ranging from 4.7% to 12.1%. Sensitivity was low for tender points 1 to 4 ranging from 6.8% to 34.6%. Specificity was high for tender points 1 to 4 ranging from 95.2% to 97.9%., Conclusions: The prevalence of lateral epicondylitis differs markedly based on case definition used, ranging more than two-fold. Standardization of a case definition is essential to allow for comparisons across studies.

Goal : We aimed to identify electroencephalographic (EEG) signal fluctuations within independent components (ICs) that correlate to spontaneous blood oxygenation level dependent (BOLD) activity in regions of the default mode network (DMN) during eyes-closed resting state. Methods : We analyzed simultaneously acquired EEG and functional magnetic resonance imaging (fMRI) eyes-closed resting state data in a convenience sample of 30 participants. IC analysis (ICA) was used to decompose the EEG time-series and common ICs were identified using data-driven IC clustering across subjects. The IC time courses were filtered into seven frequency bands, convolved with a hemeodynamic response function (HRF) and used to model spontaneous fMRI signal fluctuations across the brain. In parallel, group ICA analysis was used to decompose the fMRI signal into ICs from which the DMN was identified. Frequency and IC cluster associated hemeodynamic correlation maps obtained from the regression analysis were spatially correlated with the DMN. To investigate the reliability of our findings, the analyses were repeated with data collected from the same subjects 1 year later. Results : Our results indicate a relationship between power fluctuations in the delta, theta, beta and gamma frequency range and the DMN in different EEG ICs in our sample as shown by small to moderate spatial correlations at the first measurement (0.234 < |r| < 0.346, p < 0.0001). Furthermore, activity within an EEG component commonly identified as eye movements correlates with BOLD activity within regions of the DMN. In addition, we demonstrate that correlations between EEG ICs and the BOLD signal during rest are in part stable across time. Discussion : We show that ICA source separated EEG signals can be used to investigate electrophysiological correlates of the DMN. The relationship between the eye movement component and the DMN points to a behavioral association between DMN activity and the level of eye movement or the presence of neuronal activity in this component. Previous findings of an association between frontal midline theta activity and the DMN were replicated.

The ancient mechanisms that caused developmental gene regulatory networks to diversify among distantly related taxa are not well understood. Here we use ancestral protein reconstruction, biochemical experiments, and developmental assays of transgenic animals carrying reconstructed ancestral genes to investigate how the transcription factor Bicoid (Bcd) evolved its central role in anterior-posterior patterning in flies. We show that most of Bcd's derived functions are attributable to evolutionary changes within its homeodomain (HD) during a phylogenetic interval >140 million years ago. A single substitution from this period (Q50K) accounts almost entirely for the evolution of Bcd's derived DNA specificity in vitro. In transgenic embryos expressing the reconstructed ancestral HD, however, Q50K confers activation of only a few of Bcd's transcriptional targets and yields a very partial rescue of anterior development. Adding a second historical substitution (M54R) confers regulation of additional Bcd targets and further rescues anterior development. These results indicate that two epistatically interacting mutations played a major role in the evolution of Bcd's controlling regulatory role in early development. They also show how ancestral sequence reconstruction can be combined with in vivo characterization of transgenic animals to illuminate the historical mechanisms of developmental evolution., Competing Interests: QL, PO, RD, JR, US, MB, SS, JT No competing interests declared, (© 2018, Liu et al.)

Objective: The aim of the study was to assess the relationship between leisure time exercise and whether workers ever had modified duty or lost time (MD/LT) due to low back pain (LBP) in an occupational cohort., Methods: Workers (N = 827) completed a structured interview assessing characteristics of their LBP, whether or not the pain caused modified or lost work time, and their participation in leisure time exercise. Odds ratio of modified/lost time and minutes of exercise participation were assessed., Results: Workers who participated in over 316 min/wk of leisure time exercise incurred significantly less modified/lost time, adjusted odds ratio = 0.46 (95% confidence interval, 0.23 to 0.98). There also lies a significant trend between increases in leisure time exercise and reductions in modified/lost time (P = 0.0016)., Conclusion: These results suggest exercise reduces risk of MD/LT from LBP.

Research on meditation is advancing, but few studies about the motivations of meditators exist. Additionally, many forms and traditions of meditation have yet to be investigated. This study addresses both of these issues by presenting an overview of different forms of motivations found in contemporary Anthroposophic meditation practice. 30 Anthroposophic meditators were interviewed about their meditation experiences. The interviews were examined using thematic analysis. 14 data-driven themes were extracted and organized within a framework consisting of three superordinate theory-driven forms of motivation: External, internal and service. A developmental trajectory running from external and internal to service motivations is indicated. This approach improves upon a scheme developed by Shapiro by including additional types of motivations and being able to differentiate between forms of motivations that are fundamentally different: Self-related (heteronomous and autonomous) motivations and other-related motivations., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Working-age adults are disproportionately impacted by opioid misuse. Factors associated with opioid misuse in people with workers compensation (WC) claims are not well studied. WC in some states is a "captured" market making it a more efficient site for researching the opioids epidemic. A pilot study was conducted to identify factors associated with opioid use using a large WC insurer's claims in Utah., Methods: This was a case-control study using a large WC insurer's database. We conducted secondary data analyses of a de-identified dataset originally obtained from the WC insurer. Cases were defined as claims with a morphine equivalent dose (MED)≥50 mg/d in the 30 days after the claim was filed while controls = 0 mg/d., Results: A total of 76 patient's claims (28 cases and 48 controls) were included in the final data analyses. The majority of claimants were male (N = 50, 65.8 percent), worked full time (N = 58, 76.3 percent) and had a mean age of 37.0±11.4 years. The majority of controls filed medical only claims (N = 40, 83.3 percent) while the majority of cases filed indemnity claims (N = 19, 67.9 percent). Cases were prescribed a mean MED of 126.4 (SD = 93.3) within the first month after filing the claim. Most cases visited>3 medical providers (N = 13, 46.4 percent) in the first month after filing the claim while the majority of controls only visited one provider (N = 28, 58.3 percent). Remarkably, the mean number of providers visited within the first month for the cases was 3.8, which was 2-fold greater than the control group. Exploratory multivariate analyses showed that cases were 4.6 times more likely to have visited 2-3 medical providers (p = 0.025), and 41.8 times more likely to have visited more than three medical providers (p < 0.001). Cases had 3.6 higher odds of having been prescribed nonsteroidal anti-inflammatory prescription within the first month as compared to controls (p = 0.014)., Conclusion: This pilot study found risk factors, some of which may be modifiable. We aim to conduct a large study using existing WC data to create a scoring system that identifies those claimants at higher risk of adverse opioid-related events that may have preventive applications at a systems-level.

Our focus of attention naturally fluctuates between different sources of information even when we desire to focus on a single object. Focused attention (FA) meditation is associated with greater control over this process, yet the neuronal mechanisms underlying this ability are not entirely understood. Here, we hypothesize that the capacity of attention to transiently focus and swiftly change relates to the critical dynamics emerging when neuronal systems balance at a point of instability between order and disorder. In FA meditation, however, the ability to stay focused is trained, which may be associated with a more homogeneous brain state. To test this hypothesis, we applied analytical tools from criticality theory to EEG in meditation practitioners and meditation-naïve participants from two independent labs. We show that in practitioners-but not in controls-FA meditation strongly suppressed long-range temporal correlations (LRTC) of neuronal oscillations relative to eyes-closed rest with remarkable consistency across frequency bands and scalp locations. The ability to reduce LRTC during meditation increased after one year of additional training and was associated with the subjective experience of fully engaging one's attentional resources, also known as absorption. Sustained practice also affected normal waking brain dynamics as reflected in increased LRTC during an eyes-closed rest state, indicating that brain dynamics are altered beyond the meditative state. Taken together, our findings suggest that the framework of critical brain dynamics is promising for understanding neuronal mechanisms of meditative states and, specifically, we have identified a clear electrophysiological correlate of the FA meditation state., (© 2018 Wiley Periodicals, Inc.)

Introduction: Previous studies have reported higher wrist ratios (WR) related to carpal tunnel syndrome (CTS) but have not assessed effect modification by obesity and may have inadequately controlled for confounders., Methods: Baseline data of a multicenter prospective cohort study were analyzed. CTS was defined by nerve conduction study (NCS) criteria and symptoms., Results: Among the 1,206 participants, a square-shaped wrist was associated with CTS after controlling for confounders (prevalence ratio = 2.27; 95% confidence interval [95% CI], 1.33-3.86). Body mass index (BMI) was a strong effect modifier on the relationship between WR and both CTS and abnormal NCS results, with normal weight strata of rectangular versus square wrists = 8.18 (95% CI, 1.63-49.96) and 7.12 (95% CI, 2.19-23.16), respectively., Discussion: A square wrist is significantly associated with CTS after controlling for confounders. Effect modification by high BMI masked the eightfold magnitude adjusted relationship seen between WR and CTS among normal weight participants. Muscle Nerve 56: 1047-1053, 2017., (© 2017 Wiley Periodicals, Inc.)

Active transposable elements (TEs) may result in divergent genomic insertion and abundance patterns among conspecific populations. Upon secondary contact, such divergent genetic backgrounds can theoretically give rise to classical Dobzhansky-Muller incompatibilities (DMI), thus contributing to the evolution of endogenous genetic barriers and eventually causing population divergence. We investigated differential TE abundance among conspecific populations of the nonbiting midge Chironomus riparius and evaluated their potential role in causing endogenous genetic incompatibilities between these populations. We focussed on a Chironomus-specific TE, the minisatellite-like Cla-element, whose activity is associated with speciation in the genus. Using a newly generated and annotated draft genome for a genomic study with five natural C. riparius populations, we found highly population-specific TE insertion patterns with many private insertions. A significant correlation of the pairwise F ST estimated from genomewide single-nucleotide polymorphisms (SNPs) and the F ST estimated from TEs is consistent with drift as the major force driving TE population differentiation. However, the significantly higher Cla-element F ST level due to a high proportion of differentially fixed Cla-element insertions also indicates selection against segregating (i.e. heterozygous) insertions. With reciprocal crossing experiments and fluorescent in situ hybridization of Cla-elements to polytene chromosomes, we documented phenotypic effects on female fertility and chromosomal mispairings. We propose that the inferred negative selection on heterozygous Cla-element insertions may cause endogenous genetic barriers and therefore acts as DMI among C. riparius populations. The intrinsic genomic turnover exerted by TEs may thus have a direct impact on population divergence that is operationally different from drift and local adaptation., (© 2017 John Wiley & Sons Ltd.)

We report a systematic spectroscopical investigation of three plagioclase particles (RB-QD04-0022, RA-QD02-0025-01, and RA-QD02-0025-02) returned by the Hayabusa spacecraft from the asteroid Itokawa, by means of scanning electron microscopy, cathodoluminescence microscopy/spectroscopy, and micro-Raman spectroscopy. The cathodoluminescence properties are used to evaluate the crystallization effects and the degree of space weathering processes, especially the shock-wave history of Itokawa. They provide new insights regarding spectral changes of asteroidal bodies due to space weathering processes. The cathodoluminescence spectra of the plagioclase particles from Itokawa show a defect-related broad band centered at around 450 nm, with a shoulder peak at 425 nm in the blue region, but there are no Mn- or Fe-related emission peaks. The absence of these crystal field-related activators indicates that the plagioclase was formed during thermal metamorphism at subsolidus temperature and extreme low oxygen fugacity. Luminescence characteristics of the selected samples do not show any signatures of the shock-induced microstructures or amorphization, indicating that these plagioclase samples suffered no (or low-shock pressure regime) shock metamorphism. Cathodoluminescence can play a key role as a powerful tool to determine mineralogy of fine-grained astromaterials.

Bone Morphogenetic Proteins (BMPs) pattern the dorsal-ventral axis of bilaterian embryos; however, their roles in the evolution of body plan are largely unknown. We examined their functional evolution in fly embryos. BMP signaling specifies two extraembryonic tissues, the serosa and amnion, in basal-branching flies such as Megaselia abdita , but only one, the amnioserosa, in Drosophila melanogaster . The BMP signaling dynamics are similar in both species until the beginning of gastrulation, when BMP signaling broadens and intensifies at the edge of the germ rudiment in Megaselia , while remaining static in Drosophila . Here we show that the differences in gradient dynamics and tissue specification result from evolutionary changes in the gene regulatory network that controls the activity of a positive feedback circuit on BMP signaling, involving the tumor necrosis factor alpha homolog eiger . These data illustrate an evolutionary mechanism by which spatiotemporal changes in morphogen gradients can guide tissue complexity., Competing Interests: The authors declare that no competing interests exist.

Application and interpretation of statistical evaluation of relationships is a necessary element in biomedical research. Statistical analyses rely on P value to demonstrate relationships. The traditional level of significance, P<0.05, can be negatively impacted by small sample size, bias, and random error, and has evolved to include interpretation of statistical trends, correction factors for multiple analyses, and acceptance of statistical significance for P>0.05 for complex relationships such as effect modification., Competing Interests: The authors have no conflicts of interest to declare.

Background: Transplantation (NTX) associated ischemia-reperfusion-mechanisms and the predisposition for insulin resistance are discussed as causes of a posttransplantation diabetes mellitus (PTDM). Furthermore, immunosuppressants can have a damaging effect on insulin secretion., Methods: 55 metabolically healthy patients with an endstage renal disease (age 52 ± 14 years, body mass index 27 ± 5 kg / m(2), blood pressure 137 ± 15/82 ± 11 mmHg) were included in a prospectively cohort study. These patients were transplanted between 2009 and 2011 (82 % of the NTX patients). Baseline examination was performed before NTX. Within the 2nd week as well as 6 and 12 months after transplantation an oral glucose tolerance test (oGGT), 3 and 9 months after NTX a glucagon test took place. In these connections the determination of plasma glucose, C-peptide and insulin was performed. Study endpoints were: graft failure, impaired glucose tolerance (iGT), PTDM, patient's death., Results: Over a follow-up-period of 1 year post NTX iGT / PTDM occurred in 31 % and graft failure in 13 %. In comparison with the healthy control group patients with iGT / PTDM were older (59 ± 8 vs. 48 ± 14ys, p = 0.001), overweight (BMI 29 ± 4 vs. 26 ± 5 kg / m(2), p = 0.038), showed an indication of an insulin resistance before NTX (HOMA 4.0 ± 2.9 vs. 2.4 ± 1.4, p = 0.013; C-peptide 10.1 ± 5.2 vs. 7.1 ± 3.6 ng / ml, p = 0.014; insulin 14.6 ± 9.4 vs. 10.6 ± 5.5mU / l, p = 0.045) and higher HbA1c levels (5.6 ± 0.5 vs. 5.4 ± 0.4 %, p = 0.032). Age (p = 0.001), fasting plasma glucose (p = 0.042), the glucose levels of oGTT immediately after transplantation were shown as prognostically relevant (fasting glucose: p = 0.027; 1 h: p = 0.014; 2 h: p = 0.002). An isolated defective secretion as a result of a toxic damage to the β-cells by immunosuppressants couldn't be shown in any of the patients with iGT / PTDM. 4 % of the patients died in the first year after NTX., Conclusion: In 31 % a disorder of glucose metabolism was found as a frequent complication after NTX. The HOMA index was found to be a meaningful marker for an existing insulin resistance. The fasting glucose before and an oGTT in the first weeks after NTX showed itself as clinically valid laboratory parameters for a risk assessment., (© Georg Thieme Verlag KG Stuttgart · New York.)

The number of insect species that are amenable to functional genetic studies is growing rapidly and provides many new research opportunities in developmental and evolutionary biology. The holometabolous insects represent a disproportionate percentage of animal diversity and are thus well positioned to provide model species for a wide variety of developmental processes. Here we discuss emerging holometabolous models, and review some recent breakthroughs. For example, flies and midges were found to use structurally unrelated long-range pattern organizers, butterflies and moths revealed extensive pattern formation during oogenesis, new imaging possibilities in the flour beetle Tribolium castaneum showed how embryos break free of their extraembryonic membranes, and the complex genetics governing interspecies difference in head shape were revealed in Nasonia wasps., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: This study assesses relationships between the Framingham cardiovascular disease risk (CVD risk) score and prevalence of US Department of Transportation (DOT)-reportable crashes in commercial motor vehicle (CMV) drivers, after controlling for potential confounders., Methods: Data were analyzed from CMV drivers (N = 797) in a large cross-sectional study. CVD risk was calculated for each driver. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) between CVD risk and DOT-reportable crashes were calculated., Results: Drivers in the two highest CVD risk groups had significantly higher likelihood of crash (OR = 2.08, 95% CI = 1.20 to 3.63 and OR = 1.99, 95% CI = 1.05 to 3.77, respectively) after adjusting for confounders. There was a significant trend of increasing prevalence of crashes with an increasing CVD risk score (P = 0.0298)., Conclusion: Drivers with a high CVD risk had a higher likelihood of a crash after controlling for confounders.

Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional "value." In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters C max, t max, and area under the curve (AUC) were determined in plasma within the interval of 0-12 h. When comparing the ratio estimates of AUC and C max for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism.

Morphogenetic functions of the amnioserosa, the serosa, the amnion, and the yolk sac are reviewed on the basis of recent studies in flies (Drosophila, Megaselia), beetles (Tribolium), and hemipteran bugs (Oncopeltus). Three hypotheses are presented. First, it is suggested that the amnioserosa of Drosophila and the dorsal amnion of other fly species function in a similar manner. Second, it is proposed that in many species with an amniotic cavity, the amnion determines the site of serosa rupture, which, through interactions between the serosa and the amnion, enables the embryo to break free from the amniotic cavity and to close its backside. Finally, it is concluded that the yolk sac is likely an important player in insect morphogenesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The abundances of (92)Nb and (146)Sm in the early solar system are determined from meteoritic analysis, and their stellar production is attributed to the p process. We investigate if their origin from thermonuclear supernovae deriving from the explosion of white dwarfs with mass above the Chandrasekhar limit is in agreement with the abundance of (53)Mn, another radionuclide present in the early solar system and produced in the same events. A consistent solution for (92)Nb and (53)Mn cannot be found within the current uncertainties and requires the (92)Nb/(92)Mo ratio in the early solar system to be at least 50% lower than the current nominal value, which is outside its present error bars. A different solution is to invoke another production site for (92)Nb, which we find in the α-rich freezeout during core-collapse supernovae from massive stars. Whichever scenario we consider, we find that a relatively long time interval of at least ∼ 10 My must have elapsed from when the star-forming region where the Sun was born was isolated from the interstellar medium and the birth of the Sun. This is in agreement with results obtained from radionuclides heavier than iron produced by neutron captures and lends further support to the idea that the Sun was born in a massive star-forming region together with many thousands of stellar siblings.

Although research on the effects of mindfulness meditation (MM) is increasing, still very little has been done to address its influence on the white matter (WM) of the brain. We hypothesized that the practice of MM might affect the WM microstructure adjacent to five brain regions of interest associated with mindfulness. Diffusion tensor imaging was employed on samples of meditators and non-meditators (n = 64) in order to investigate the effects of MM on group difference and aging. Tract-Based Spatial Statistics was used to estimate the fractional anisotrophy of the WM connected to the thalamus, insula, amygdala, hippocampus, and anterior cingulate cortex. The subsequent generalized linear model analysis revealed group differences and a group-by-age interaction in all five selected regions. These data provide preliminary indications that the practice of MM might result in WM connectivity change and might provide evidence on its ability to help diminish age-related WM degeneration in key regions which participate in processes of mindfulness.

Objective: This large, cross-sectional study calculated prevalence of disorders and assessed factors associated with self-reported lifetime crashes., Methods: Truck drivers (n = 797) completed computerized questionnaires reporting crashes, demographics, psychosocial factors, and other elements, as well as had taken measurements (eg, height, weight, serum, and blood pressure)., Results: Most drivers were male (n = 685, 85.9%), and the mean body mass index was 32.9 ± 7.5  kg/m2 with 493 (61.9%) being obese. Many drivers (n = 326, 39.9%) experienced at least one, with 132 (16.6%) having multiple, lifetime, reportable crashes. Many factors were associated with crashes, including increasing age, increasing truck driving experience, male sex, alcohol, low back pain, heart disease, and feeling tense. The most consistent associations with crashes were pulse pressure, cell phone use, and feeling physically exhausted after work., Conclusions: Modifiable factors associated with self-reported crashes were identified. These suggest targeted interventions may reduce risks of crashes.

Objective: To ascertain worker health characteristics and psychosocial factors associated with changes in body weight and total cholesterol (TC) among two production operation populations., Methods: We performed descriptive and predictive analysis of questionnaire data and biomedical measurements from two prospective cohort studies. Our key outcomes were changes in weight, and TC over 5 to 10 years between baseline and exit assessments., Results: A total of 146 subjects were analyzed. Increases in weight were associated with belief in being overweight and baseline overweight and obesity. Increases in TC levels were associated with female sex, belief that TC levels were "not good," and feeling depressed., Conclusions: Most of the reported associations with increases in weight and TC levels are amenable to interventions and may be a target for workplace intervention programs.

In the fruit fly Drosophila, head formation is driven by a single gene, bicoid, which generates head-to-tail polarity of the main embryonic axis. Bicoid deficiency results in embryos with tail-to-tail polarity and no head. However, most insects lack bicoid, and the molecular mechanism for establishing head-to-tail polarity is poorly understood. We have identified a gene that establishes head-to-tail polarity of the mosquito-like midge, Chironomus riparius. This gene, named panish, encodes a cysteine-clamp DNA binding domain and operates through a different mechanism than bicoid. This finding, combined with the observation that the phylogenetic distributions of panish and bicoid are limited to specific families of flies, reveals frequent evolutionary changes of body axis determinants and a remarkable opportunity to study gene regulatory network evolution., (Copyright © 2015, American Association for the Advancement of Science.)

Objective: To describe demographic and health characteristics, and factors associated with obesity among production workers., Methods: This cross-sectional study analyzed baseline data from two occupational cohorts. Regression modeling was used to assess associations between worker characteristics and obesity., Results: A total of 1974 subjects were included in these analyses. The mean body mass index was 29.5 kg/m (SD = 6.5). Having smoked in the past and currently smoking decreased the odds of being obese in the WISTAH Distal Upper Extremity cohort, whereas those feeling depressed had increased odds of being obese. Being a Pacific Islander/Native Hawaiian and married increased the odds of obesity in the BackWorks Low Back Pain cohort., Conclusions: Factors associated with obesity differed substantially between the two cohorts. Recognizing factors associated with obesity in specific work settings may provide opportunities for optimizing preventive workplace interventions.

Background: The high prevalence of obesity among commercial truck drivers may be related to sedentary nature of the job, lack of healthy eating choices, and lack of exercise. There may be a link between obesity and crash risk, therefore an intervention to reduce obesity in this population is needed., Objective: To assess feasibility of a 12-week weight loss intervention for truck drivers with a weight loss goal of 10% of initial body weight., Methods: Drivers were selected based on age (≥21 years) and body mass index (≥30 kg/m^2). The drivers participated in a before-after clinical trial. The intervention included a 12-week program that provided information on healthy diet and increasing exercise, and telephone-based coaching using SMART goals. Outcomes included change from baseline in reported energy intake, measured weight, waist, hip, and neck circumference, blood pressure, and point of care capillary blood lipids and hemoglobin A1c. Exit interviews were conducted to gain insight into driver opinions on the program features and usefulness. This study was registered with the NIH Clinical Trials Registry, number NCT02348983., Results: 12 of 13 drivers completed the study. Weight loss was statistically significant (p=0.03). Reported energy (p=0.005), total fat consumption (p=0.04), and saturated fat consumption (p=0.02) intake were also lower after the 12-week intervention. Drivers attributed their weight loss to health coaching and suggested a longer intervention so that they could reach their goal and become accustomed to the changes., Conclusion: This weight loss intervention is feasible for this difficult population. Additional research is needed to compare this intervention with a control group.

Objective: To assess the readiness to change dietary intake and body weight among production workers. We also ascertained differences between self-perceived and measured body mass index., Methods: This cross-sectional study queried physical activity, psychosocial factors, fruit and vegetable intake, and readiness to change based on the transtheoretical model., Results: Sixty-three (28%) workers were overweight, and 114 (50%) were obese. Obese workers were in the following stages of weight change: precontemplation (4%), contemplation (45%), preparation (13%), action (21%), and (17%) maintenance. Ten percent of overweight workers erroneously reported their body mass index to be normal., Conclusions: About half of overweight/obese workers were in the precontemplation or contemplation stages for healthy dietary changes or weight loss. Recognizing the stages of change with regard to weight and the self-perception of weight status may help tailor workplace health promotion programs.

The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring 'quantitative system drift'. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.

Different sources of folate may have different bioavailability and hence may impact the standard definition of folate equivalents. In order to examine this, a short term human study was undertaken to evaluate the relative native folate bioavailabilities from spinach, Camembert cheese and wheat germs compared to pteroylmonoglutamic acid as the reference dose. The study had a single-centre, randomised, four-treatment, four-period, four-sequence, cross-over design, i.e. the four (food) items to be tested (referred to as treatments) were administered in sequences according to the Latin square, so that each experimental treatment occurred only once within each sequence and once within each study period. Each of the 24 subjects received the four experimental items separated by a 14-day equilibrium phase and received a pteroylmonoglutamic acid supplement for 14 days before the first testing and between the testings for saturation of body pools. Folates in test foods, plasma and urine samples were determined by stable isotope dilution assays, and in urine and plasma, the concentrations of 5-methyltetrahydrofolate were evaluated. Standard non-compartmental methods were applied to determine the biokinetic parameters C(max), t(max) and AUC from baseline corrected 5-methyltetrahydrofolate concentrations within the interval from 0 to 12 hours. The variability of AUC and C(max) was moderate for spinach and oral solution of pteroylmonoglutamic acid but high for Camembert cheese and very high for wheat germs. The median t(max) was lowest for spinach, though t(max) showed a high variability among all treatments. When comparing the ratio estimates of AUC and C(max) for the different test foods, highest bioavailability was found for spinach followed by that for wheat germs and Camembert cheese. The results underline the dependence of folate bioavailability on the type of food ingested. Therefore, the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents has to be questioned and requires further investigation.

Purpose: Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice., Methods: Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay., Results: A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity., Conclusion: Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

Controversy continues as to whether chloromethane (CH3Cl) detected during pyrolysis of Martian soils by the Viking and Curiosity Mars landers is indicative of organic matter indigenous to Mars. Here we demonstrate CH3Cl release (up to 8 μg/g) during low temperature (150-400°C) pyrolysis of the carbonaceous chondrite Murchison with chloride or perchlorate as chlorine source and confirm unequivocally by stable isotope analysis the extraterrestrial origin of the methyl group (δ(2)H +800 to +1100‰, δ(13)C -19.2 to +10‰,). In the terrestrial environment CH3Cl released during pyrolysis of organic matter derives from the methoxyl pool. The methoxyl pool in Murchison is consistent both in magnitude (0.044%) and isotope signature (δ(2)H +1054 ± 626‰, δ(13)C +43.2 ± 38.8‰,) with that of the CH3Cl released on pyrolysis. Thus CH3Cl emissions recorded by Mars lander experiments may be attributed to methoxyl groups in undegraded organic matter in meteoritic debris reaching the Martian surface being converted to CH3Cl with perchlorate or chloride in Martian soil. However we cannot discount emissions arising additionally from organic matter of indigenous origin. The stable isotope signatures of CH3Cl detected on Mars could potentially be utilized to determine its origin by distinguishing between terrestrial contamination, meteoritic infall and indigenous Martian sources.

Background: Low Back Pain (LBP) is a common and costly problem, with variation in prevalence. Epidemiological reports of rating of pain intensity and location within the low back area are rare. The objective is to describe LBP in a large, multi-center, occupational cohort detailing both point and 1-month period prevalence of LBP by location and intensity measures at baseline., Methods: In this cross-sectional report from a prospective cohort study, 828 participants were workers enrolled from 30 facilities performing a variety of manual material handling tasks. All participants underwent a structured interview detailing pain rating and location. Symptoms in the lower extremities, demographic and other data were collected. Body mass indices were measured. Outcomes are pain rating (0-10) in five defined lumbar back areas (i) LBP in the past month and (ii) LBP on the day of enrollment. Pain ratings were reported on a 0-10 scale and subsequently collapsed with ratings of 1-3, 4-6 and 7-10 classified as low, medium and high respectively., Results: 172 (20.8%) and 364 (44.0%) of the 828 participants reported pain on the day of enrollment or within the past month, respectively. The most common area of LBP was in the immediate paraspinal area with 130 (75.6%) participants with point prevalence LBP and 278 (77.4%) with 1-month period prevalence reported having LBP in the immediate paraspinal area. Among those 364 reporting 1-month period prevalence pain, ratings varied widely with 116 (31.9%) reporting ratings classified as low, 170 (46.7%) medium and 78 (21.4%) providing high pain ratings in any location. Among the 278 reporting 1-month period prevalence pain in the immediate paraspinal area, 89 (32.0%) reported ratings classified as low, 129 (46.4%), medium and 60 (21.6%) high pain ratings., Conclusions: Pain ratings varied widely, however less variability was seen in pain location, with immediate paraspinal region being the most common. Variations may suggest different etiological factors related to LBP. Aggregation of different locations of pain or different intensities of pain into one binary classification of LBP may result in loss of information which may potentially be useful in prevention or treatment of LBP.

Among the short-lived radioactive nuclei inferred to be present in the early solar system via meteoritic analyses, there are several heavier than iron whose stellar origin has been poorly understood. In particular, the abundances inferred for (182)Hf (half-life = 8.9 million years) and (129)I (half-life = 15.7 million years) are in disagreement with each other if both nuclei are produced by the rapid neutron-capture process. Here, we demonstrate that contrary to previous assumption, the slow neutron-capture process in asymptotic giant branch stars produces (182)Hf. This has allowed us to date the last rapid and slow neutron-capture events that contaminated the solar system material at ~100 million years and ~30 million years, respectively, before the formation of the Sun., (Copyright © 2014, American Association for the Advancement of Science.)

Objective: The American College of Occupational and Environmental Medicine has updated the treatment guidelines in its Elbow Disorders chapter through revision processes begun in 2006. This abbreviated version of that chapter highlights some of the evidence and recommendations developed., Methods: Comprehensive systematic literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel and extensive peer-review to develop evidence-based guidance. Consensus recommendations were formulated when evidence was lacking and often relied on analogy to other disorders for which evidence exists. A total of 108 high- or moderate-quality trials were identified for elbow disorders., Results: Guidance has been developed for 13 major diagnoses and includes 270 specific recommendations., Conclusion: Quality evidence is now available to guide treatment for elbow disorders, particularly for lateral epicondylalgia.

Religions are evolutionary selected social and cultural phenomena. They represent today belief and normative systems on which the main parts of our culture are based. For a long time religions have been seen as mainly originating from a spectrum of religious experiences. These include a broad spectrum of experiences and are astonishingly widespread in the population. The most consistent and transculturally uniform religious experiences are the mystical experiences. Only these (and the prayer experience) have factually been researched in detail neurobiologically. This article presents a review of empirical results and hypothetical approaches to explain mystical religious experiences neurobiologically. Some of the explanatory hypotheses possess logical evidence, some are even supported by neurobiological studies, but all of them have their pitfalls and are at best partially consistent. One important insight from the evidence reviewed here is that there may be a whole array of different neurophysiological conditions which may result in the same core religious mystical experiences.