Developmental delay in Rett syndrome: data from the natural history study

Background: Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT. Methods: Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores. Data were analyzed for age at acquisition and loss of developmental features and for phenotype-genotype effects. Acquired, lost, and retained skills were compared between classic RTT and atypical RTT with better or poorer functional scores using Fisher's Exact test. To examine if the mean total score from the Motor Behavioral Assessment during follow-up differed for acquiring a skill, we used a generalized estimating equation assuming compound symmetry correlation structure within a subject. A general linear model was used to examine whether the mean age of acquisition or loss of a developmental skill differed by mutation type. P values <0.05 were considered significant and were two-sided without adjustment for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary, NC, USA). Results: Early developmental skills or abilities were often acquired albeit later than normal. More complex motor and communication acquisitions were delayed or absent. Clinical severity was less in those achieving the respective skill. Individuals with R133C, R294X, and R306C point mutations and 3′ truncations tended to have better developmental outcomes. Conclusions: Early developmental skills were acquired by many, but clear differences from normal emerged, particularly in skills expected after age 6 months. When comparing clinical severity, greater acquisition of specific skills was associated with specific mutations, confirming the impression that these mutations confer milder developmental abnormalities. These data may serve for planning and interpretation of early intervention studies in RTT. Trial registration This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination

The Vehicle, Fall 2009

Table of Contents Poetry AliveRashelle McNairpage 3 Train of ThoughtsJeanette Saribekianpage 4 Biding the TideMarlee Lutzpage 5 Rotten HarvestJessyca Revillapage 15 Nostalgia ODJustine Fittonpage 16 Beyond WordsAshley Wrightpage 26 Don\u27tMelinda Knightpage 27 Happy HourStephen Garciapage 35 UntitledDaniel Paquinpage 37 Vibrant SensationsAshton Tembypage 38 Scarecrow Sally on a Saturday NightDaniel Davispage 45 The FarmAshley Wrightpage 49 Anything ButJustine Fittonpage 51 CrashDanielle Shirtinopage 53 Weathering SatisfactionRashelle McNairpage 54 SeminarDaniel Davispage 71 Nature\u27s Mood SwingsJeanette Saribekianpage 72 The PerformanceMelinda Knightpage 68 AmaterasuMarlee Lutzpage 82 Prose AirLauren Davidsonpage 6 The Twang of OrangesJ.T. Dawsonpage 18 ListenStephani Pescitellipage 29 The Rise and Fall of NickNickolas Alexanderpage 30 LossSimyona Deanovapage 39 Like DiamondsMark Rheaumepage 42 Moral FixationBryan Rolfsenpage 47 Reflections in College AlgebraNicole Reichertpage 52 LeashDaniel Paquinpage 56 I Lost My KeysJustine Fittonpage 75 A Third Grade EssayMark Rheaumepage 69 Be Careful, They BiteDaniel Davispage 84 Art Limb BurgAlycia Rockeycover AvesSamantha Flowerspage 14 Life-LuminescenceStephani Pescitellipage 25 MonopolyMegan Mathypage 28 Carousel NostalgiaAlycia Rockeypage 36 ShoesSarah Olsonpage 41 Waimea BayJarrod Taylorpage 50 Peacock Plumage Alycia Rockeypage 55 Building a HouseStephani Pescitellipage 70 ShellMegan Mathypage 74 From the VacationSamantha Flowerspage 73 Chicago CanopyAlycia Rockeypage 83 Features Editor\u27s NoteLindsey Durbinpage 1 LazarusDr. David Radavichpage 2 James K. Johnson Creative Writing Awardpage 88 Winning Entries (Poetry)Matthew J. Schumakepage 89 Winning Entry (Nonfiction)Jennifer O\u27Neilpage 92 Interview, 2009 Chapbook WinnerDaniel Davispage 95 Contributorspage 99https://thekeep.eiu.edu/vehicle/1090/thumbnail.jp

The Vehicle, Fall 2009

Table of Contents Poetry AliveRashelle McNairpage 3 Train of ThoughtsJeanette Saribekianpage 4 Biding the TideMarlee Lutzpage 5 Rotten HarvestJessyca Revillapage 15 Nostalgia ODJustine Fittonpage 16 Beyond WordsAshley Wrightpage 26 Don\u27tMelinda Knightpage 27 Happy HourStephen Garciapage 35 UntitledDaniel Paquinpage 37 Vibrant SensationsAshton Tembypage 38 Scarecrow Sally on a Saturday NightDaniel Davispage 45 The FarmAshley Wrightpage 49 Anything ButJustine Fittonpage 51 CrashDanielle Shirtinopage 53 Weathering SatisfactionRashelle McNairpage 54 SeminarDaniel Davispage 71 Nature\u27s Mood SwingsJeanette Saribekianpage 72 The PerformanceMelinda Knightpage 68 AmaterasuMarlee Lutzpage 82 Prose AirLauren Davidsonpage 6 The Twang of OrangesJ.T. Dawsonpage 18 ListenStephani Pescitellipage 29 The Rise and Fall of NickNickolas Alexanderpage 30 LossSimyona Deanovapage 39 Like DiamondsMark Rheaumepage 42 Moral FixationBryan Rolfsenpage 47 Reflections in College AlgebraNicole Reichertpage 52 LeashDaniel Paquinpage 56 I Lost My KeysJustine Fittonpage 75 A Third Grade EssayMark Rheaumepage 69 Be Careful, They BiteDaniel Davispage 84 Art Limb BurgAlycia Rockeycover AvesSamantha Flowerspage 14 Life-LuminescenceStephani Pescitellipage 25 MonopolyMegan Mathypage 28 Carousel NostalgiaAlycia Rockeypage 36 ShoesSarah Olsonpage 41 Waimea BayJarrod Taylorpage 50 Peacock Plumage Alycia Rockeypage 55 Building a HouseStephani Pescitellipage 70 ShellMegan Mathypage 74 From the VacationSamantha Flowerspage 73 Chicago CanopyAlycia Rockeypage 83 Features Editor\u27s NoteLindsey Durbinpage 1 LazarusDr. David Radavichpage 2 James K. Johnson Creative Writing Awardpage 88 Winning Entries (Poetry)Matthew J. Schumakepage 89 Winning Entry (Nonfiction)Jennifer O\u27Neilpage 92 Interview, 2009 Chapbook WinnerDaniel Davispage 95 Contributorspage 99https://thekeep.eiu.edu/vehicle/1090/thumbnail.jp

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411

‘I don’t mind watching him cum’: Heterosexual men, threesomes, and the erosion of the one-time rule of homosexuality

In this qualitative research, conducted on 30 gay-friendly, heterosexual, undergraduate men, we examine actual and hypothetical experiences of sexual threesomes, both with two women and one man (FFM), and two men and one woman (MMF). We show a cultural willingness for heterosexual men to engage in not only FFM threesomes, but also MMF threesomes. A year and a half into their university experience, seven of our participants had had at least one FFM threesome, and five of our participants had had at least one MMF threesome. We argue that this threesome experience is a component of cultural progression toward a more liberal, recreational culture of sexuality that encourages play and experimentation instead of a procreative model of sexuality. Thus, this research contributes to the growing body of literature showing that the cultural boundaries of heterosexuality are rapidly expanding for males, permitting more same-sex sexual contact without triggering the one-time-rule of homosexuality

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial