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Cardiac transplantation has become limited by a critical shortage of suitable organs from brain-dead donors. Reports describing the successful clinical transplantation of hearts donated after circulatory death (DCD) have recently emerged. Hearts from DCD donors suffer significant ischemic injury prior to organ procurement; therefore, the traditional approach to the transplantation of hearts from brain-dead donors is not applicable to the DCD context. Advances in our understanding of ischemic post-conditioning have facilitated the development of DCD heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement. The availability of a clinically approved heart perfusion device now allows DCD heart preservation in a normothermic beating state and minimizes exposure to incremental cold ischemia. This technology also facilitates assessments of organ viability to be undertaken prior to transplantation, thereby minimizing the risk of primary graft dysfunction. The application of a tailored approach to DCD heart transplantation that focuses on organ resuscitation at the time of procurement, preservation, and pre-transplant assessments of organ viability has facilitated the successful clinical application of DCD heart transplantation. The transplantation of hearts from DCD donors is now a clinical reality. Investigating ways to optimize the resuscitation, preservation, evaluation, and long-term outcomes is vital to ensure a broader application of DCD heart transplantation in the future.

The ProtekDuo’s dual-lumen design combined with its ability to be inserted percutaneously allows for its use in a wide variety of clinical scenarios. Therefore, it was chosen to be used as the venous cannula on cardiopulmonary bypass to treat a patient who had a high risk of right ventricular failure and a need for mechanical circulatory support postoperatively. Biventricular failure occurred during the patient’s course in hospital, and the ProtekDuo was used in a novel hybrid configuration using both the distal port on the ProtekDuo and the aortic cannula as outflow cannula for the extracorporeal membrane oxygenation circuit, and the proximal port on the ProtekDuo was used as the venous return. Gradually increasing ProtekDuo distal outflow and decreasing aortic cannula outflow facilitated an isolated and progressive loading of the left ventricle while maintaining support for the right ventricle. In total, four separate mechanical circulatory support configurations were used to support and optimize the patient’s hemodynamics. The ability to utilize a single cannula in a hybrid manner may be useful in patients requiring controlled weaning of mechanical circulatory support.

The metabolic instability of mRNA currently limits its utility for gene therapy. Compared to plasmid DNA, mRNA is significantly more susceptible to digestion by RNase in the circulation following systemic dosing. To increase mRNA metabolic stability, we hybridized a complementary reverse mRNA with forward mRNA to generate double-stranded mRNA (dsmRNA). RNase A digestion of dsmRNA established a 3000-fold improved metabolic stability compared to single-stranded mRNA (ssmRNA). Formulation of a dsmRNA polyplex using a PEG-peptide further improved the stability by 3000-fold. Hydrodynamic dosing and quantitative bioluminescence imaging of luciferase expression in the liver of mice established the potent transfection efficiency of dsmRNA and dsmRNA polyplexes. However, hybridization of the reverse mRNA against the 5′ and 3′ UTR of forward mRNA resulted in UTR denaturation and a tenfold loss in expression. Repeat dosing of dsmRNA polyplexes produced an equivalent transient expression, suggesting the lack of an immune response in mice. Co-administration of excess uncapped dsmRNA with a dsmRNA polyplex failed to knock down expression, suggesting that dsmRNA is not a Dicer substrate. Maximal circulatory stability was achieved using a fully complementary dsmRNA polyplex. The results established dsmRNA as a novel metabolically stable and transfection-competent form of mRNA.

This essay focuses on the characteristics of corpora drawn from pedagogical materials and contrasts them with the properties of corpora of larger repertoires. Two case studies show pedagogical corpora to contain relatively more chromaticism, and to devote more of their probability mass to low-frequency events. This is likely due to the formatting of and motivation behind classroom materials (for example, focusing proportionately more resources on difficult concepts). I argue that my observations challenge the utility of using pedagogical corpora within research into implicit learning. I also suggest that these datasets are uniquely situated to yield insights into explicit learning, and into how musical traditions are represented in the classroom.

Purpose Blastomyces dermatitidis is a dimorphic fungus endemic to North America capable of causing fatal respiratory failure. Acute respiratory distress syndrome (ARDS) complicates up to 10% of pulmonary blastomycosis in hospitalized patients and carries a mortality of 50-90%. This report describes the clinical course of four consecutive patients with blastomycosis-related ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO) during 2009-2014. Clinical features Four adults were referred from northwestern Ontario, Canada with progressive respiratory illnesses. All patients developed diffuse bilateral opacities on chest radiography and required mechanical ventilation within 6-72 hr. Patients satisfied Berlin criteria for severe ARDS with trough P a O 2 /F i O 2 ratios of 44-61 on positive end-expiratory pressure of 12-24 cm H 2 O. Wet mount microscopy from respiratory samples showed broad-based yeast consistent with B.dermatitidis . Despite lung protective ventilation strategies with maximal F i O 2 (patients A-D), neuromuscular blockade (patients A-D), inhaled nitric oxide (patients A and D), and prone positioning (patient D), progressive hypoxemia resulted in initiation of venovenous ECMO by hours 24-90 of mechanical ventilation with subsequent de-escalation of ventilatory support. In all four cases, ECMO decannulation was performed (7-23 days), mechanical ventilation was withdrawn (18-52 days), and the patients survived to hospital discharge (31-87 days). Conclusion This report describes the successful application of ECMO as rescue therapy in aid of four patients with refractory blastomycosis-associated ARDS. In addition to early appropriate antimicrobial therapy, transfer to an institution experienced with ECMO should be considered when caring for patients from endemic areas with rapidly progressive respiratory failure.

The Yale-Classical Archives Corpus (YCAC) contains harmonic and rhythmic information for a dataset of Western European Classical art music. This corpus is based on data from classicalarchives.com, a repository of thousands of user-generated MIDI representations of pieces from several periods of Western European music history. The YCAC makes available metadata for each MIDI file, as well as a list of pitch simultaneities (\"salami slices\") in the MIDI file. Metadata include the piece's composer, the composer's country of origin, date of composition, genre (e.g., symphony, piano sonata, nocturne, etc.), instrumentation, meter, and key. The processing step groups the file's pitches into vertical slices each time a pitch is added or subtracted from the texture, recording the slice's offset (measured in the number of quarter notes separating the event from the file's beginning), highest pitch, lowest pitch, prime form, scale-degrees in relation to the global key (as determined by experts), and local key information (as determined by a windowed key-profile analysis). The corpus contains 13,769 MIDI files by 571 composers yielding over 14,051,144 vertical slices. This paper outlines several properties of this corpus, along with a representative study using this dataset.

In The Lancet, Abbas Ardehali and colleagues report findings from their open-label, non-inferiority PROCEED II trial in which 130 heart-transplant patients were randomly assigned to receive a standard-criteria donor heart preserved with either the Organ Care System--an ex-vivo heart perfusion platform that maintains the heart in a warm, beating, and unloaded state--or conventional cold static storage.

This article investigates several questions of harmonic function using aggressively data-driven approaches. We apply Hidden Markov Modeling—a technique used to identify contextual regularities within streams of data—to the Kostka-Payne, McGill Billboard, and Bach chorale corpora. The resulting models question the generalizability of the traditional three-function model, illustrating the syntactic uniqueness of various corpora while also highlighting recurrent characteristics of tonal repertories. Finally, this article offers some general observations, including questioning the role that tonal hierarchy plays in theories of function and discussing the cultural politics inherent in assuming the universality of one functional system.