Fearless: Christine Serwan and Sam Holmes

This week, we’re recognising the fearless work that Christine Serwan ’13 and Sam Holmes ’13 will be doing over the next two years during with the Peace Corps. [excerpt

Strategies to Incorporate Left Atrial Appendage Occlusion Into Clinical Practice

AbstractThe left atrial appendage (LAA) has been identified as a predominant source of thrombus formation leading to significant thromboembolic events in patients with nonvalvular atrial fibrillation. Medical therapy to eliminate thrombus formation in the LAA has been the standard of care for several decades, but mechanical approaches designed to exclude the LAA from the circulation have recently been developed. The largest body of randomized and nonrandomized data to date has been for the Watchman device (Boston Scientific, Natick, Massachusetts), which was recently approved by the Food and Drug Administration for selected patients in the United States. There are no current guidelines or guidance for institutions and operators looking to become involved in this therapy. This perspective is aimed at exploring these issues and providing necessary information and guidance to these programs and operators to help ensure a successful launch of a LAA occlusion program and optimize patient selection, procedural performance, and outcome

Assassins and apples: the environmental constraints of two snails that threaten Australian aquatic systems

Context: Alien freshwater snails pose a substantial risk to Australian native aquatic biota.Aims: This study aims to determine the thermal and salinity ranges of two introduced species within Australia, Pomacea sp. and Anentome sp., to facilitate predictions of their potential geographic range should they become widely established.Methods: Laboratory tests were conducted to assess behavioural responses of snails to altered temperature or salinity after different acclimation regimes.Key results: After acclimation at 25°C, Pomacea sp. had a median activity range of 13.5–38°C and Anentome sp. of 12–38.5°C. Higher acclimation temperatures produced observable effects, whereas lower acclimation temperatures did not. Salinity tolerances differed, with Pomacea sp. remaining active at up to 8 parts per thousand (ppt) (after acclimation at 25°C), with acclimation at 20°C resulting in a lower salinity tolerance. By contrast, Anentome sp. snails were active at up to 5 ppt after low salinity acclimation, demonstrating enhanced salinity tolerance compared with non-salinity acclimations.Conclusions: These results showed that both snails are capable of surviving temperatures and salinities that would allow invasion into subtropical and warm-temperate Australian aquatic systems.Implications: Free from the constraints of natural predators, competitors, and parasites, these snails should be of great concern to biosecurity agencies in Australia

Population structure and connectivity of tiger sharks (Galeocerdo cuvier) across the Indo-Pacific Ocean basin

Population genetic structure using nine polymorphic nuclear microsatellite loci was assessed for the tiger shark () at seven locations across the Indo-Pacific, and one location in the southern Atlantic. Genetic analyses revealed considerable genetic structuring ( > 0.14,

Catheter-based intervention for pulmonary vein stenosis due to fibrosing mediastinitis: The Mayo Clinic experience

AbstractIntroductionFibrosing mediastinitis (FM) is a rare but fatal disease characterized by an excessive fibrotic reaction in the mediastinum, which can lead to life-threatening stenosis of the pulmonary veins (PV). Catheter-based intervention is currently the only viable option for therapy. However, the current literature on how best to manage these difficult cases, especially in regards to sequential interventions and their potential complications is very limited.MethodsWe searched through a database of all patients who have undergone PV interventions at the Earl H. Wood Cardiac Catheterization Laboratory in Mayo Clinic, Rochester. From this collection, we selected patients that underwent PV intervention to relieve stenosis secondary to FM.ResultsEight patients were identified, with a mean age of 41years (24–59years). Five were men, and three were women. Three patients underwent balloon angioplasty alone, and five patients had stents placed. The majority of patients had acute hemodynamic and symptomatic improvement. More than one intervention was required in five patients, four patients had at least one episode of restenosis, and four patients died within four weeks of their first PV intervention.ConclusionsWe describe the largest reported case series of catheter-based intervention for PV stenosis in FM. Although catheter-based therapy improved hemodynamics, short-term vascular patency, and patient symptoms, the rate of life-threatening complications, restenosis, and mortality associated with these interventions was found to be high. Despite these associated risks, catheter-based intervention is the only palliative option available to improve quality of life in severely symptomatic patients with PV stenosis and FM. Patients with PV stenosis and FM (especially those with bilateral disease) have an overall poor prognosis in spite of undergoing these interventions due to the progressive and recalcitrant nature of the disease. This underscores the need for further innovative approaches to manage this disease

Engaging with History after Macpherson

The Race Relations Amendment Act (2000) identifies a key role for education, and more specifically history, in promoting ‘race equality’ in Britain. In this article Ian Grosvenor and Kevin Myers consider the extent of young people’s current engagement with the history of ‘diversity, change and immigration’ which underpins the commitment to ‘race equality’. Finding that in many of Britain’s schools and universities a singular and exclusionary version of history continues to dominate the curriculum, they go on to consider the reasons for the neglect of multiculturalism. The authors identify the development of an aggressive national identity that depends on the past for its legitimacy and argue that this sense of the past is an important obstacle to future progress

Functional correlates of clinical phenotype and severity in recurrent SCN2A variants

In SCN2A-related disorders, there is an urgent demand to establish efficient methods for determining the gain- (GoF) or loss-of-function (LoF) character of variants, to identify suitable candidates for precision therapies. Here we classify clinical phenotypes of 179 individuals with 38 recurrent SCN2A variants as early-infantile or later-onset epilepsy, or intellectual disability/autism spectrum disorder (ID/ASD) and assess the functional impact of 13 variants using dynamic action potential clamp (DAPC) and voltage clamp. Results show that 36/38 variants are associated with only one phenotypic group (30 early-infantile, 5 later-onset, 1 ID/ASD). Unexpectedly, we revealed major differences in outcome severity between individuals with the same variant for 40% of early-infantile variants studied. DAPC was superior to voltage clamp in predicting the impact of mutations on neuronal excitability and confirmed GoF produces early-infantile phenotypes and LoF later-onset phenotypes. For one early-infantile variant, the co-expression of the alpha(1) and beta(2) subunits of the Na(v)1.2 channel was needed to unveil functional impact, confirming the prediction of 3D molecular modeling. Neither DAPC nor voltage clamp reliably predicted phenotypic severity of early-infantile variants. Genotype, phenotypic group and DAPC are accurate predictors of the biophysical impact of SCN2A variants, but other approaches are needed to predict severity. A comprehensive biophysical analysis of disease-associated mutations in the voltage-gated sodium channel gene, SCN2A, suggests that dynamic action potential clamp may be a better predictor than voltage clamp of how these mutations alter neuronal excitability, though other approaches are needed to predict severity

Infection Rate and Outcomes of Watchman Devices: Results from a Single-Center 14-Year Experience

The Watchman device (WD) is a commonly used alternative strategy to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation who have an increased bleeding risk. There are rare case reports of WD-related infection. Currently, there is no formal study that has systematically evaluated the incidence and outcomes WD-related infections. The objective of this study was to evaluate the incidence, risk factors, and outcomes for WD-associated infections in a single-center cohort over a 14-year period. All patients who underwent WD implantation over a 14-year study period (July 2004 through December 2018) comprised our cohort. Baseline characteristics, procedural data, and postimplantation events were identified through a retrospective chart review. Primary study outcomes included WD-related infection, other cardiovascular device-related infection, bacteremia, and mortality. A total of 181 patients (119 males; 65.7%) with a mean age of 75 years at implantation were included in the analysis. A total of 534.7 patient years of follow-up was accrued, with an average of 2.9 years per patient. The most common indications for implantation included gastrointestinal bleeding (56 patients; 30.9%) and intracerebral bleeding (51 patients; 28.2%). During the follow-up period, 37 (20.4%) patients died. Six developed evidence of bacteremia. Only 1 developed an implantable cardioverter defibrillator infection that required a complete system extraction. None of the cohort developed a WD-related device infection during the study period. We concluded that there is a low risk of WD-related infection even in the setting of a blood stream infection