Exploring Communication Patterns in the Discussion of Maternal PKU Syndrome Between Parents and Daughters

Maternal PKU syndrome is the collection of features and birth defects that arise from uncontrolled phenylalanine levels in a pregnant woman with phenylalanine hydroxylase (PAH) deficiency, previously known as phenylketonuria (PKU). Currently, the literature is lacking in exploring what young women are being told about maternal PKU syndrome. In this study, communication patterns between parents and their daughters about maternal PKU syndrome were investigated through an online survey completed by parents. The survey assessed parents’ level of comfort with this topic, the information they discussed with their daughter and the resources they accessed. Followup interviews were conducted with participants to elaborate on survey responses. The majority of participants were very comfortable discussing maternal PKU syndrome (51%); however, 21% reported being very uncomfortable with the discussion. Parents most often discussed health concerns associated with maternal PKU syndrome (94%) and least frequently discussed unplanned pregnancies (58%). The most frequently used resource was a metabolic doctor (73%); however, parents included mothers with PAH deficiency among the most helpful resources. Themes from open-ended responses and interviews emphasized qualities of parents’ discussion with their daughters. Parents commented on the timing and how they presented the information to their daughters. They described challenges such as the emotional impact of the conversation as well as their daughter’s decision-making and consequences of her actions. Lastly, they discussed advice for treatment compliance, resources, and ways to normalize the topic of maternal PKU syndrome. These results can help genetic counselors better understand the parent daughter conversation so that healthcare professionals can better assess and inform families about maternal PKU syndrome

A Review of Discourse Analysis in Literacy Research: Equitable Access

This review represents research employing discourse analysis conducted by scholars interested in literacy issues in education across the age span—preschool to adult—during the last 10 years. Drawing from more than 300 studies, we discerned that a common theme was understanding how the literacy education of all students can be successfully accomplished. We organized the review into two complementary sections. The first section highlights discourse analytic approaches taken to investigate: Whose literacies count? Which literacies count? The second section explains the contributions the studies made organized according to five questions: What are literate identities, how are they constructed, and by whom? How are disciplinary knowledges, discourses, and identities constructed? How can schools provide students with access to school‐based literacies? What are the shifting roles of literacy teachers and learners within and outside of school? How does discourse analysis research address movement within and across literacy sites and practices in a contemporary, globalized, and increasingly digitally influenced world? تلخيص البحث: تمثل هذه المراجعة الأبحاث التي يوجد فيها تحليل الخطاب الذي قام به الباحثون المهتمون بشؤون تعلم القراءة والكتابة في التعليم عبر الأعمار—من الروضة حتى بالغ سن الرشد—في السنوات العشرة الماضية. لقد حددنا موضوعاً مشتركاً من استجماع أكثر من 300 دراسة وهو الطريقة التي قد يتم فيها تعليم القراءة والكتابة لجميع الطلاب بالنجاح. وقد نظمنا المراجعة في قسمين متكاملين الأول يسلط الضوء على طرق الخطاب التحليلية المأخوذة للتحقيق في: لمن معارف القراءة والكتابة التي نحتاج إلى أخذها بعين الاعتبار؟ وأية معارف من هذه يجب الأخذ في الحسبان؟ والقسم الثاني يشرح مساهمات الدراسات المندرجة تحت الأصناف المبنية على خمسة أسئلة: ما هي هويات معرفة القراءة والكتابة وكيف يتم تشكيلها ومن يشكلها؟ وكيف يتم تشكيل المعارف الدراسية والخطابية والهوية؟ وكيف تستطيع المدارس أن توفر الطلاب بوسيلة للمعارف القائمة في المدرسة؟ ما هي الأدوار المتغيرة لمعلمي القراءة والكتابة وطلابهم داخل المدرسة وخارجها؟ وكيف يعالج التحليل الخطابي الحركات في مواقع القراءة والكتابة وعبرها وكذلك الممارسات التي تتم في عالم معاصر عولمي فيه يزداد التأثير الرقمي؟ 本文旨在阐述过去10年期间，学者致力于不同学龄（由学前以至成人）的读写教育问题研究时所使用的语篇分析方法。作者从300多个研究里整理出一个共通的主题，就是去理解如何使到所有学生的读写教育取得成功。本文献综述是由两个互补的章节组成。第一节重点介绍研究调查所采用的两个语篇分析的处理方法：是谁的读写文化有重要意义？哪些读写文化有重要意义？第二节根据五个问题来阐釋这些研究的贡献：1.有读写文化的人的身份认同，所指的是什么？是怎样建构而成的？由谁所建构而成的？2.各种学科知识、话语及身份认同是如何建构而成的？3.学校如何为学生提供获取校本读写文化知识的门路？4.读写教学教师与学生在校内及校外在角色上有什么转移？5.在当前全球化和日益受数码化影响的世界中，语篇分析研究如何处理流动于各种写文化网站以内及之间的文化信息及各种文化实践的问题？ Cet état de la question présente l'analyse du discours dans les recherches des chercheurs qui s'intéressent aux questions de littératie en éducation— du niveau préscolaire à l'adulte — au cours des dix dernières années. En nous basant sur plus de 300 études, une préoccupation commune nous est apparue qui est de comprendre comment l'enseignement de la littératie peut permettre à tous les élèves de réussir. Nous avons organisé l'état de la question en deux parties complémentaires. La première partie s'intéresse au discours des approches analytiques réalisées pour étudier les questions suivantes: prendre en compte les littératies de qui ? prendre en compte quelles littératies? La seconde partie explique ce qu'ont apporté les études effectuées en réponse à cinq questions: que sont les identités lettrées ? comment sont‐elles construites, et par qui ? Comment sont construits les avoirs disciplinaires, les discours, et les identités ? Comment les écoles fournissent‐elles aux élèves un accès aux littératies basées sur l'école ? Quels sont les changements de rôles des professeurs de littératie et des apprenants dans l'école et hors de celle‐ci ? Comment le discours de la recherche analysé prend‐il en compte le mouvement au sein et au travers des sites de littératie et des pratiques dans un monde contemporain globalisé et de plus en plus influencé par l'informatique. В этом обзоре представлены исследования, проведенные на протяжении последних десяти лет с помощью дискурс‐анализа и посвященные проблемам развития грамотности людей разного возраста – от дошкольников до взрослых. Общая тема для более чем трехсот рассмотренных авторами источников: как добиться успеха в становлении грамотности? Обзор состоит из двух взаимодополняющих разделов. В первом описаны подходы к анализу дискурса, которые помогают понять, что принимается за образцы грамотности и кто может им соответствовать. Во втором разделе результаты исследований рассмотрены согласно пяти категориям: Как человек осознает себя в плане грамотности, на чем и кем строится эта идентичность? Как конструируется предметное или дисциплинарное знание, дискурс и идентичность? Как может школа дать учащимся доступ к школьной академической грамотности? В чем состоят и как меняются роли преподавателей грамотности и учащихся в стенах школы и за ее пределами? Как исследования дискурс‐анализа отражают перемещения участников дискурса в реальном и виртуальном пространстве в современном глобализированном мире? Este repaso presenta investigación que ha sido llevada a cabo usando análisis del discurso por estudiosos interesados en cuestiones de alfabetización en la educación a todas las edades—preescolar hasta adulto—en los últimos diez años. Al examinar más de 300 estudios, vimos que un tema común es el de entender cómo lograr exitosamente la educación de competencias de todos los estudiantes. Organizamos el repaso en dos secciones complementarias. Enfocamos la primera en los acercamientos analíticos del discurso que se han usado para investigar: ¿Cuáles competencias cuentan o valen? ¿Las competencias de quiénes cuentan o valen? La segunda sección explica las contribuciones que hicieron los estudios organizadas de acuerdo a cinco temas: ¿Qué son identidades competentes, cómo se construyen, y por quiénes? ¿Cómo se construyen el conocimiento, el discurso y las identidades de las disciplinas? ¿Cómo pueden las escuelas darles acceso a los estudiantes a las competencias basadas en la escuela? ¿Cuáles son los papeles cambiantes de los maestros y los estudiantes de competencias dentro y fuera de la escuela? ¿Cómo plantea la investigación del análisis del discurso el movimiento dentro y a través de los sitios de competencias y prácticas en este mundo contemporáneo, globalizado y digital?Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88086/1/RRQ.45.1.5.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme