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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. 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. 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). 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. UK National Institute for Health Research Health Technology Assessment Programme.

Purim, which will take place on Monday evening, is celebrated by gatherings in synagogues, dressing in outlandish costumes, hearing the biblical book titled \"The Scroll of Esther,\" and using noisemakers, called graggers, everytime the name of Haman is mentioned in the Scroll. While all of this seems like a lot of fun -- and it is -- there is a serious side to the background and meaning of this day.

I then know it will not be long until the annual news article that will concern some community or individual upset with a holiday display in a public area or in a classroom. I know that I am not the only person who dreads this. In spring 1996, a speech made by Rabbi Robert Frazin of Temple Solel at the Brotherhood/Sisterhood Banquet of the Inter-Faith Council caused me much concern. After meeting with him, it was apparent that he and I shared a common concern for the unity of our spiritual community. And so, in May 1996, we called a meeting of community spiritual leaders. The meeting was attended by the Revs. Roger Woehl of First Presbyterian Church of Hollywood, Richard Compton of First Baptist of Hollywood, Dewitt Sheffield of First Christian Church of Hollywood, Allen Ressor of Cooper City Church of God; Roger Miller, executive director of the HIV Pastoral Care Network; Rabbi Harold Richter, a Jewish chaplain; Rabbi Frazin of Temple Solel; Father Sean Mulcahy of St. Maurice Catholic Church in Hollywood and me. Together we drafted a mission statement as follows:

Organic ferroelectrics with switchable electrical polarization would be an attractive prospect for applications if their Curie temperature—below which these materials display ferroelectric behaviour—could be raised to room temperature or above; this goal has now been achieved with a family of organic materials characterized by a supramolecular structural motif. Effective organic ferroelectrics Ferroelectric materials exhibit spontaneous electric polarization that can be reversed by the application of an external electric field. Organic ferroelectrics would be an attractive prospect for applications if their Curie temperature (the temperature below which ferroelectric behaviour kicks in) could be raised to room temperature or above. Alok Tayi and colleagues have now achieved this goal with a family of organic materials that seem to owe their properties to a supramolecular structural motif, in which the component molecules not only form dipole-generating charge-transfer pairs but also assemble into ordered, three-dimensional hydrogen-bonded networks. These materials could find application in sensors and energy-efficient memories, and their underlying molecular architecture could help to guide the development of other functional organic systems that can switch under the influence of electric fields at ambient temperatures. Materials exhibiting a spontaneous electrical polarization 1 , 2 that can be switched easily between antiparallel orientations are of potential value for sensors, photonics and energy-efficient memories. In this context, organic ferroelectrics 3 , 4 are of particular interest because they promise to be lightweight, inexpensive and easily processed into devices. A recently identified family of organic ferroelectric structures is based on intermolecular charge transfer, where donor and acceptor molecules co-crystallize in an alternating fashion known as a mixed stack 5 , 6 , 7 , 8 : in the crystalline lattice, a collective transfer of electrons from donor to acceptor molecules results in the formation of dipoles that can be realigned by an external field as molecules switch partners in the mixed stack. Although mixed stacks have been investigated extensively, only three systems are known 9 , 10 to show ferroelectric switching, all below 71 kelvin. Here we describe supramolecular charge-transfer networks that undergo ferroelectric polarization switching with a ferroelectric Curie temperature above room temperature. These polar and switchable systems utilize a structural synergy between a hydrogen-bonded network and charge-transfer complexation of donor and acceptor molecules in a mixed stack. This supramolecular motif could help guide the development of other functional organic systems that can switch polarization under the influence of electric fields at ambient temperatures.

Then I turned around and read a newspaper from New Jersey and found out that a young physicist, born in Mississippi, whose father was shot when he was 6 years old, went to Chicago with his young mother, bathed in tears over the death of his father, tried to go to school. The gangs ran him out. Finally went to a parochial school; the sisters put their arms around him. The next thing he knew he was graduated and went on to the University of Illinois, finished with honors in nuclear physics, from there went to Dartmouth with a master's degree in experimental physics, from there to Berkeley with a Ph.D. This article was saying he'd been hired by Rutgers University and AT&T regarded him as one of the singular outstanding laser physicists in the world and built for him a multimillion-dollar laboratory where he could experiment with laser physicists to his heart's delight. \"Moreover, Mr. [de Tocqueville], we are not giving up something. I get a pension every month from the Teachers Insurance Annuity Association, the biggest pension fund in the world, $88 billion, and for the last 20 years it's been headed by a black man. He hasn't lost a dime. I get my check every month in my bank. And I will tell you one more thing, Mr. de Tocqueville, you were wrong. The Ford Foundation has had a black executive for 20 years. Former football player. Lawyer Frank Thomas hasn't lost a dime. Billions of dollars of endowment, hundreds of millions of dollars a year. He hasn't lost a nickel. No bad audits. As I was driving in North Carolina the other day, I thought about what Mr. de Tocqueville said. He said there was no way possible for blacks to make it in this society. What Mr. de Tocqueville did not know is that emancipation soon would take place. As I would drive across the state, you know what I've found out. Twelve black colleges are existing, all of them started within 25 years of the Emancipation Proclamation.

We present our stance on teaching programming with the aim of increasing reflexivity amongst university educators through dissecting and destroying pervasive anti-pedagogical gendered framings. From the so-called male geek trope that dominates Global North/Western perceptions of technology to the actively anti-feminist stances such demographics espouse: programming has a sexism problem. Herein, we touch on how and why programming is so gendered in the present; we expound on how we manage this in our classrooms and in our mentorship relationships; and we explain how to keep doing so moving forwards. Through weaving examples of programming into the text, it is demonstrated that basic coding concepts can be conveyed with little effort. Additionally, example dialogues – exchanges between teachers and students and between educators – are worked through to counteract inappropriate or harmful framings. Finally, we list some ground rules, concrete dos and don’ts, for us to consider going forwards. Ultimately, as educators, we have a twofold obligation, for our students to a) learn programming, and for them to b) unlearn problematic perceptions of who can code.

Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC.

Lifetime noise exposure is generally quantified by self-report. The accuracy of retrospective self-report is limited by respondent recall but is also bound to be influenced by reporting procedures. Such procedures are of variable quality in current measures of lifetime noise exposure, and off-the-shelf instruments are not readily available. The Noise Exposure Structured Interview (NESI) represents an attempt to draw together some of the stronger elements of existing procedures and to provide solutions to their outstanding limitations. Reporting is not restricted to prespecified exposure activities and instead encompasses all activities that the respondent has experienced as noisy (defined based on sound level estimated from vocal effort). Changing exposure habits over time are reported by dividing the lifespan into discrete periods in which exposure habits were approximately stable, with life milestones used to aid recall. Exposure duration, sound level, and use of hearing protection are reported for each life period separately. Simple-to-follow methods are provided for the estimation of free-field sound level, the sound level emitted by personal listening devices, and the attenuation provided by hearing protective equipment. An energy-based means of combining the resulting data is supplied, along with a primarily energy-based method for incorporating firearm-noise exposure. Finally, the NESI acknowledges the need of some users to tailor the procedures; this flexibility is afforded, and reasonable modifications are described. Competency needs of new users are addressed through detailed interview instructions (including troubleshooting tips) and a demonstration video. Limited evaluation data are available, and future efforts at evaluation are proposed.

Although there is strong histological evidence for age-related synaptopathy in humans, evidence for the existence of noise-induced cochlear synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of synaptopathy.