Little is known about the induction period before the nucleation and growth of colloidal semiconductor quantum dots. Here, we introduce an approach that allows us to probe intermediates present in ...the induction period. We show that this induction period itself exhibits distinct stages with the evolution of the intermediates, first without and then with the formation of covalent bonds between metal cations and chalcogenide anions. The intermediates are optically invisible in toluene, while the covalent-bonded intermediates become visible as magic-size clusters when a primary amine is added. Such evolution of magic-size clusters provides indirect but compelling evidence for the presence of the intermediates in the induction period and supports the multi-step nucleation model. Our study reveals that magic-size clusters could be readily engineered in a single-size form, and suggests that the existence of the intermediates during the growth of conventional quantum dots results in low product yield.
Abstract
The current manuscript is the second update of the original Practical Guide, published in 2013 Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral ...anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625–651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467–1507. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug–drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).
Nucleation has been generally acknowledged as a rapid but uncontrollable process that is difficult to decouple from the subsequent growth phase. Here, we report our finding that nucleation of ...semiconductor magic-size clusters (MSCs) can be well-regulated, without a subsequent evolution in size. Colloidal semiconductor CdS MSCs were synthesized by a two-step approach intentionally designed, without the simultaneous formation of nanocrystals of other sizes. The nuclei MSCs exhibit a sharp optical absorption peaking at 311 nm and are thus denoted by MSC–311. We prepared the immediate precursor for MSC–311 denoted by IP311 which is liquid-like, through a reaction which was normally performed to grow CdS conventional quantum dots (QDs), but at a different temperature (180 °C) prior to the nucleation and growth of CdS QDs. We demonstrate that the nucleation of MSC–311 from IP311 followed first order kinetics remarkably well, and the presence of a small amount of methanol accelerated this process effectively. Moreover, the liquid-like prenucleation cluster IP311 and the nuclei MSC–311 have similar masses. Accordingly, we propose that the intramolecular reorganization of IP311 results in the nuclei MSC–311, the formation of which features a two-step nucleation pathway. The present study introduces methodology via absorption spectroscopy to monitor the nucleation kinetics of semiconductor MSCs from their immediate precursors. The repeatable, predictable, and controllable nucleation process investigated here brings a deeper insight into nucleation of other semiconductor nanocrystals and contributes to the foundation for the future development of advanced theoretical models for crystal nucleation.
Abstract
The current manuscript is the Executive Summary of the second update to the original Practical Guide, published in 2013. Non-vitamin K antagonist oral anticoagulants (NOACs) are an ...alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF), and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to co-ordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are (i) eligibility for NOACs; (ii) practical start-up and follow-up scheme for patients on NOACs; (iii) ensuring adherence to prescribed oral anticoagulant intake; (iv) switching between anticoagulant regimens; (v) pharmacokinetics and drug–drug interactions of NOACs; (vi) NOACs in patients with chronic kidney or advanced liver disease; (vii) how to measure the anticoagulant effect of NOACs; (viii) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (ix) how to deal with dosing errors; (x) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (xi) management of bleeding under NOAC therapy; (xii) patients undergoing a planned invasive procedure, surgery or ablation; (xiii) patients requiring an urgent surgical intervention; (xiv) patients with AF and coronary artery disease; (xv) avoiding confusion with NOAC dosing across indications; (xvi) cardioversion in a NOAC-treated patient; (xvii) AF patients presenting with acute stroke while on NOACs; (xviii) NOACs in special situations; (xix) anticoagulation in AF patients with a malignancy; and (xx) optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA web site (www.NOACforAF.eu).
Background
We report a kindred referred for molecular investigation of severe hemophilia A in a young female in which extremely skewed X‐inactivation was observed in both the proband and her ...clinically normal mother.
Methods
Bidirectional Sanger sequencing of all F8 gene coding regions and exon/intron boundaries was undertaken. Methylation‐sensitive restriction enzymes were utilized to investigate skewed X‐inactivation using both a classical human androgen receptor (HUMARA) assay, and a novel method targeting differential methylation patterns in multiple informative X‐chromosome SNPs. Illumina Whole‐Genome Infinium microarray analysis was performed in the case‐parent trio (proband and both parents), and the proband's maternal grandmother.
Results
The proband was a cytogenetically normal female with severe hemophilia A resulting from a heterozygous F8 pathogenic variant inherited from her similarly affected father. No F8 mutation was identified in the proband's mother, however, both the proband and her mother both demonstrated completely skewed X‐chromosome inactivation (100%) in association with a previously unreported 2.3 Mb deletion at Xp22.2. At least three disease‐associated genes (FANCB, AP1S2, and PIGA) were contained within the deleted region.
Conclusions
We hypothesize that true “extreme” skewing of X‐inactivation (≥95%) is a rare occurrence, but when defined correctly there is a high probability of finding an X‐chromosome disease‐causing variant or larger deletion resulting in X‐inactivation through a survival disadvantage or cell lethal mechanism. We postulate that the 2.3 Mb Xp22.2 deletion identified in our kindred arose de novo in the proband's mother (on the grandfather's homolog), and produced extreme skewing of X‐inactivation via a “cell lethal” mechanism. We introduce a novel multitarget approach for X‐inactivation analysis using multiple informative differentially methylated SNPs, as an alternative to the classical single locus (HUMARA) method. We propose that for females with unexplained severe phenotypic expression of an X‐linked recessive disorder trio‐SNP microarray should be undertaken in combination with X‐inactivation analysis.
We report a kindred referred for molecular investigation of severe hemophilia A in a young female in which extremely skewed X‐inactivation was observed in both the proband and her clinically normal mother. No F8 mutation was identified in the proband's mother, however both the proband and her mother demonstrated completely skewed X‐chromosome inactivation in association with a previously unreported 2.3 Mb deletion at Xp22.2
Pregnancy and delivery are critical times for women with bleeding disorders, with mothers, and possibly their affected infants, being exposed to a variety of haemostatic challenges. Management of ...women with bleeding disorders during pregnancy involves a multidisciplinary team including, but not limited to, an obstetrician, an anaesthetist and a haematologist. This consensus document from the Australian Haemophilia Centre Directors' Organisation (AHCDO) provides practical information for clinicians managing women with bleeding disorders during pregnancy. Included are: the expected physiological response in pregnancy in such women; management of pregnancy, labour and delivery, as well as obstetric anaesthesia issues, postpartum care, and reducing and treating postpartum haemorrhage; and management of infants at risk of a bleeding disorder and of bleeding in neonates. The guidelines were developed after extensive consultation, face-to-face meetings and revisions. The final document represents a consensus opinion of all AHCDO members. Where evidence is lacking, recommendations are based on clinical experience and consensus opinion.
Poniższy tekst jest streszczeniem drugiej aktualizacji oryginalnego praktycznego przewodnika opublikowanego w 2013 roku. Leki przeciwkrzepliwe niebędące antagonistami witaminy K (NOAC) stanowią cenną ...alternatywę dla antagonistów witaminy K (VKA) w zapobieganiu udarom u pacjentów z migotaniem przedsionków (AF) i uznano je za leki preferowane, szczególnie dla osób rozpoczynających leczenie przeciwkrzepliwe. Zarówno lekarze, jak i pacjenci przyzwyczajają się do ich stosowania w praktyce klinicznej, istnieje jednak wiele nierozwiązanych kwestii dotyczących optymalnego stosowania tych leków w określonych sytuacjach klinicznych. Europejskie Stowarzyszenie Zaburzeń Rytmu Serca (EHRA, European Heart Rhythm Association) podjęło się koordynacji opracowania jednolitego sposobu komunikowania się z lekarzami na temat stosowania różnych preparatów NOAC. Grupa określiła 20 tematów zawierających konkretne scenariusze kliniczne, w odniesieniu do których sformułowano praktyczne wskazówki na podstawie dostępnych dowodów. Do problemów klinicznych należą: 1) odpowiednia kwalifikacja pacjentów do leczenia; 2) praktyczne schematy rozpoczynania oraz monitorowania terapii za pomocą NOAC; 3) zagwarantowanie przestrzegania zaleceń przyjmowania doustnych leków przeciwkrzepliwych; 4) zmiana schematów leczenia przeciwkrzepliwego; 5) farmakokinetyka oraz interakcje lekowe; 6) stosowanie NOAC u osób z przewlekłą chorobą nerek i zaawansowaną chorobą wątroby; 7) sposoby pomiaru efektu przeciwkrzepliwego NOAC; 8) pomiar stężenia NOAC w surowicy: rzadkie wskazania, środki ostrożności, potencjalne „pułapki”; 9) postępowanie w przypadku pomyłki w dawkowaniu; 10) postępowanie w przypadku (podejrzenia) przedawkowania bez krwawienia lub badania krzepnięcia wskazujące na potencjalne ryzyko krwawienia; 11) postępowanie w przypadku krwawienia w trakcie terapii za pomocą NOAC; 12) postępowanie u pacjentów poddanych planowym zabiegom chirurgicznym, procedurom inwazyjnym czy ablacji; 13) postępowanie u pacjentów wymagających pilnej interwencji chirurgicznej; 14) pacjenci z AF oraz chorobą wieńcową; 15) unikanie pomyłek w dawkowaniu NOAC w różnych wskazaniach; 16) kardiowersja u pacjenta leczonego NOAC; 17) AF u pacjentów z ostrym udarem mózgu leczonych NOAC; 18) NOAC w sytuacjach szczególnych; 19) leczenie przeciwkrzepliwe w przypadku AF u pacjentów z nowotworami złośliwymi; 20) optymalizacja leczenia za pomocą VKA. Dodatkowe informacje oraz materiały do pobrania, jak również karty leczenia przeciwkrzepliwego w kilku językach można znaleźć na stronie internetowej EHRA (www.NOACforAF.eu).
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