54 J pulses with 18 nm bandwidth from a diode-pumped chirped-pulse amplification laser system.

We report on results from the fully diode-pumped chirped-pulse amplification laser system Polaris. Pulses were amplified to a maximum energy of 54.2 J before compression. These pulses have a full width at half-maximum spectral bandwidth of 18 nm centered at 1033 nm and are generated at a repetition rate of 0.02 Hz. To the best of our knowledge, these are the most energetic broadband laser pulses generated by a diode-pumped laser system so far. Due to the limited size of our vacuum compressor, only attenuated pulses could be compressed to a duration of 98 fs containing an energy of 16.7 J, which leads to a peak power of 170 TW. These pulses could be focused to a peak intensity of 1.3×1021 W/cm2. Having an ultra-high temporal contrast of 1012 with respect to amplified spontaneous emission these laser pulses are well suited for high-intensity laser-matter experiments.

Comparison study of in vivo dose response to laser-driven versus conventional electron beam.

The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.

Mitral Leaflet Shortening as an Ancillary Procedure in Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Mitral leaflet elongation is common in hypertrophic cardiomyopathy (HCM), contributes to obstructive physiology, and presents a challenge to the dual surgical goals of abolition of outflow gradients and abolition of mitral regurgitation. Anterior leaflet shortening, performed as an ancillary surgical procedure during myectomy, is controversial. METHODS: This was a retrospective study of all patients undergoing myectomy from January 2010 to March 2020, with analysis of survival and echocardiographic results. The study compared outcomes of patients treated with myectomy and concomitant mitral leaflet shortening with patients treated with myectomy alone. Over this time, the technique for mitral shortening evolved from anterior leaflet plication to residual leaflet excision (ReLex). RESULTS: Myectomy was performed in 416 patients aged 57.5 ± 13.6 years, and 204 (49%) patients were female. Average follow-up was 5.4 ± 2.8 years. Survival follow-up was complete in 415 patients. Myectomy without valve replacement was performed in 332 patients, of whom 192 had mitral valve shortening (58%). Mitral leaflet plication was performed in 73 patients, ReLex in 151, and both procedures in 32. Hospital mortality for patients undergoing myectomy was 0.7%. At 8 years, cumulative survival was 95% for both the myectomy combined with leaflet shortening group and the myectomy alone group, with no difference in survival between the 2 groups. There was no difference in survival between the anterior leaflet plication and ReLex groups. Echocardiography 2.5 years after surgery showed a decrease in resting and provoked gradients, mitral regurgitation, and left atrial volume and no difference in key variables between patients who underwent ancillary leaflet shortening and patients who underwent myectomy alone. CONCLUSIONS: These results affirm that mitral shortening may be an appropriate surgical judgment for selected patients.

Clinical course of adults with co-occurring hypertrophic cardiomyopathy and hypertension: A scoping review.

Introduction: Hypertension affects approximately 50 % of patients with hypertrophic cardiomyopathy (HCM) but clinical course in adults with co-occurring HCM and hypertension is underexplored. Management may be challenging as routine anti-hypertensive medications may worsen obstructive HCM, the most common HCM phenotype. In this scoping review, we sought to synthesize the available literature related to clinical course and outcomes in adults with both conditions and to highlight knowledge gaps to inform future research directions. Methods: We searched 5 electronic databases (PubMed, CINAHL, Scopus, Embase, Web of Science) to identify peer-reviewed articles, 2011-2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guideline. Results: Eleven articles met eligibility. Adults with both conditions were older and had higher rates of obesity and diabetes than adults with HCM alone. Results related to functional class and arrhythmia were equivocal in cross-sectional studies. Only 1 article investigated changes in medical therapy among adults with both conditions. Hypertension was a predictor of worse functional class, but was not associated with all-cause mortality, heart failure-related mortality, or sudden-death. No data was found that related to common hypertension-related outcomes, including renal disease progression, nor patient-reported outcomes, including quality of life. Conclusions: Our results highlight areas for future research to improve understanding of co-occurring HCM and hypertension. These include a need for tailored approaches to medical management to optimize outcomes, evaluation of symptom burden and quality of life, and investigation of hypertension-related outcomes, like renal disease and ischemic stroke, to inform cardiovascular risk mitigation strategies.

Unmasking Obstruction in Hypertrophic Cardiomyopathy With Postprandial Resting and Treadmill Stress Echocardiography.

BACKGROUND: Latent left ventricular outflow tract obstruction (LVOTO) is an important cause of symptoms in patients with hypertrophic cardiomyopathy (HCM) but can be challenging to provoke. OBJECTIVES AND METHODS: To examine the value of postprandial resting and stress echocardiography and utilization of invasive or enhanced drug therapies (surgical myectomy, alcohol septal ablation, disopyramide, and mavacamten) in patients with postprandial LVOTO. Consecutive HCM patients without LVOTO underwent routine and postprandial echocardiography at rest, with provocation (Valsalva and standing) and after symptom-limited treadmill stress. RESULTS: Among 252 patients (mean age, 58 years, 39% women), postprandial LVOT gradients were higher compared with routine echocardiography at rest (median, 9.0 [0-38.0] vs 0 [0-14.0] mm Hg; P < .0001) and with provocation (18.5 [0-70.3] vs 1.5 [0-41.0] mm Hg; P < .0001). Postprandial exercise stress echocardiogram (PPXSE) gradients were higher in a subset of 44 patients who underwent both postprandial and fasting stress echocardiography (47.0 [5.3-81.0] vs 17.5 [0-46.0] mm Hg; P < .0001). In total, 49 (19.5%) patients achieved the ≥50 mm Hg threshold under routine conditions (rest/provocation); 90 (35.7%) additional patients achieved postprandial gradients ≥50 mm Hg (rest/provocation/exercise), 38 (15.1%) with PPXSE alone. A total of 71 patients were treated with 91 invasive or enhanced drug therapies, 32 (45.1%) of whom had gradients ≥50 mm Hg only after eating (rest/provocation) and 8 (11.3%) only with PPXSE, with symptom relief in the majority. CONCLUSIONS: Postprandial echocardiography was useful at unmasking LVOTO in more than one-third of patients who did not have high gradients otherwise. Eating before echocardiography is a powerful provocative tool in the evaluation of patients with HCM.

Clinical Course and Treatment of Patients With Apical Aneurysms Due to Hypertrophic Cardiomyopathy.

Background: There is controversy about risk of malignant arrhythmias and stroke in patients with apical aneurysms in hypertrophic cardiomyopathy (HCM). Objectives: The aim of this study was to estimate the associations of aneurysm size and major HCM risk factors with the incidence of lethal and potentially lethal arrhythmias and to estimate incidence of unexplained stroke. Methods: In 108 patients (age 57.4 ± 13.5 years, 37% female) from 3 HCM centers, we assessed American Heart Association/American College of Cardiology guidelines risk factors and initial aneurysm size by echocardiography and cardiac magnetic resonance imaging and assessed outcomes after median 5.9 (IQR: 3.7-10.0) years. Results: Implantable cardioverter defibrillator discharges or sudden cardiac death (SCD) occurred in 21 (19.4%) patients. Of patients with a risk factor, 55% subsequently had ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD at follow-up, compared with 10% in those who did not (P < 0.001). The upper tercile of size had a 5-year cumulative risk of 35%, while the lower tercile had 5-year risk of 6% (P = 0.0046). In those with the smallest aneurysms <2 cm2 and also without risk factors VT, VF, or SCD occurred in only 2.5%. Clinical atrial fibrillation (AF) was prevalent, occurring in 49 (45%). Stroke was commonly associated with AF. Stroke without conventional cause had an incidence of 0.5%/year. Surgery in 19% was effective in reducing symptoms. VT ablation and surgery were moderately effective in preventing recurrent VT. Conclusions: Risk factors and aneurysm size were associated with subsequent VT, VF, or SCD. Patients with aneurysms in the lowest tercile of size have a low cumulative 5-year risk. Clinical AF occurred frequently. Stroke prevalence in absence of known stroke etiologies is uncommon and comparable to risk of severe bleeding.

Clinical course and outcomes in adults with co-occurring hypertrophic cardiomyopathy and hypertension: a scoping review protocol.

INTRODUCTION: Hypertension affects 40%-60% of adults with hypertrophic cardiomyopathy (HCM), the most common inherited cardiac condition. It can be a diagnostic confounder for HCM, contributing to delayed diagnosis. Clinically, treatment of co-occurring hypertension and HCM poses challenges as first-line and second-line antihypertensive medications are often contraindicated in HCM. The clinical course in adults with hypertension and HCM is also not well understood, and studies examining patient outcomes in this population are equivocal. In this paper, we aim to outline the protocol of a scoping review, a type of literature review, to systematically synthesise existing knowledge on adults with co-occurring HCM and hypertension, highlighting knowledge and evidence gaps, and identifying future research directions to optimise outcomes in this population. METHODS AND ANALYSIS: This review is guided by Arksey and O'Malley's conceptual framework on conducting scoping reviews. We will search five electronic databases (PubMed, CINAHL, Scopus, Embase and Web of Science) and reference lists of publications to identify eligible articles focusing on medical therapy, clinical course or outcomes in adults with HCM and hypertension, between 2011 and 2023. Our search strategy and presentation of results will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guideline. First, two independent reviewers will screen articles, by title and abstract, followed by a full-text screen to identify eligible articles. Relevant data will be extracted and synthesised. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as it is a secondary data collection of published articles and does not involve human subject participation. We will present results of this review at relevant professional conferences and patient-centred educational events. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: https://osf.io/cy8qb/?view_only=98197f4850584e51807ff9b62533a706.

Weight loss in hypertrophic cardiomyopathy: A clinical case series.

Background: Obesity is prevalent among patients with hypertrophic cardiomyopathy (HCM). Obese HCM patients have greater wall thickness, LV mass, worse hemodynamic function and NYHA class. Weight loss may favorably influence the HCM phenotype. Case summary: We describe six patients with hypertrophic cardiomyopathy who lost weight through diet and lifestyle changes (n = 4) or bariatric surgery (n = 2). Radiographic imaging, with cardiac MRI or CT scan, was performed before and after their weight loss. There was a mean decrease in LV mass and indexed LV mass, and a mean numerical decrease in mean wall thickness in up to 14 out of 18 LV segments. There was also NYHA class reduction in symptoms. Discussion: In this case series, we have shown that substantial weight loss in HCM patients can be associated with a decrease in LV mass, wall thickness and improvement in symptoms. These observations indicate the potential for positive remodeling of the heart by weight loss. Prospective studies of the benefits of weight loss in HCM are needed.

Deducing the electron-beam diameter in a laser-plasma accelerator using x-ray betatron radiation.

We investigate the properties of a laser-plasma electron accelerator as a bright source of keV x-ray radiation. During the interaction, the electrons undergo betatron oscillations and from the carefully measured x-ray spectrum the oscillation amplitude of the electrons can be deduced which decreases with increasing electron energies. From the oscillation amplitude and the independently measured x-ray source size of (1.8±0.3) µm we are able to estimate the electron bunch diameter to be (1.6±0.3) µm.

COVID-19 in Adults With Hypertrophic Cardiomyopathy.

Background: Individuals with cardiovascular disease are considered high risk for severe COVID-19. However, the clinical impact of COVID-19 in patients with hypertrophic cardiomyopathy (HCM) is unknown. The purpose of this study was to describe the clinical course and outcomes of COVID-19 in patients with HCM. Methods: This retrospective observational study included adults with HCM and positive PCR/antibody test for SARS-CoV-2 at a large urban hospital system in the New York from January, 2020 to January, 2021. Results: Seventy individuals were included, with a mean (SD) age of 60.1 (15.1) years, 39 (55.7%) of whom were male, and 42 (60%) white. Forty-five (65.3%) patients had obstructive HCM. Hypertension and obesity (BMI ≥ 30) were present in 45 (64.3%) and 37 (52.9%) patients, and the prevalence of atrial fibrillation, obstructive sleep apnea and diabetes was high. Common symptoms of COVID-19 were fever, cough, shortness of breath and fatigue, affecting 33 (47.1%), 33 (47.1%), 28 (40.0%), and 28 (40.0%) patients, respectively. Fourteen (20%) patients were hospitalized. The majority (45 [64.3%] patients) recovered without intervention. Two patients had non-fatal pulmonary embolisms, 1 had atrial fibrillation requiring electrical cardioversion and 1 had acute decompensated heart failure. Three (4.3%) patients required mechanical ventilation, two of whom died (case fatality rate 2.9%). A total of 15 (21.4%) patients were asymptomatic. Conclusions: Our data suggest that in this diverse and high-risk group of patients with HCM, established risk factors for severe COVID-19, such as obesity, may be more important drivers of morbidity and mortality than the presence of HCM alone.

Basiepidermal nervous system in Nemertoderma westbladi (Nemertodermatida): GYIRFamide immunoreactivity.

The Nemertodermatida are a small group of microscopic marine worms. Recent molecular studies have demonstrated that they are likely to be the earliest extant bilaterian animals. What was the nervous system (NS) of a bilaterian ancestor like? In order to answer that question, the NS of Nemertoderma westbladi was investigated by means of indirect immunofluorescence technique and confocal scanning laser microscopy. The antibodies to a flatworm neuropeptide GYIRFamide were used in combination with anti-serotonin antibodies and phalloidin-TRITC staining. The immunostaining revealed an entirely basiepidermal NS. A ring lying outside the body wall musculature at the level of the statocyst forms the only centralisation, the "brain". No stomatogastric NS has been observed. The GYIRFamide immunoreactive part of the "brain" is formed of loosely packed nerve fibres with multiple small neurones and a few large ones. The peptidergic and aminergic patterns of the NS do not correspond to each other: the former is more developed on the ventral side, the latter is more pronounced on the dorsal side. A pair of GYIRFamide immunoreactive nerve cords innervates the ventral side of the animal, the mouth and the male genital opening. The nemertodermatids studied to-date display no common NS pattern. Possible synapomorphies of the Acoelomorpha are discussed. The study demonstrates that the nemertodermatid NS possesses a number of plesiomorphic features and appears more primitive than the NS in other worms, except the Xenoturbellida. The bilaterian ancestor supposedly possessed only a basiepidermal nerve net and had no centralised brain-like structures and no stomatogastric NS.

Optical control of hard X-ray polarization by electron injection in a laser wakefield accelerator.

Laser-plasma particle accelerators could provide more compact sources of high-energy radiation than conventional accelerators. Moreover, because they deliver radiation in femtosecond pulses, they could improve the time resolution of X-ray absorption techniques. Here we show that we can measure and control the polarization of ultra-short, broad-band keV photon pulses emitted from a laser-plasma-based betatron source. The electron trajectories and hence the polarization of the emitted X-rays are experimentally controlled by the pulse-front tilt of the driving laser pulses. Particle-in-cell simulations show that an asymmetric plasma wave can be driven by a tilted pulse front and a non-symmetric intensity distribution of the focal spot. Both lead to a notable off-axis electron injection followed by collective electron-betatron oscillations. We expect that our method for an all-optical steering is not only useful for plasma-based X-ray sources but also has significance for future laser-based particle accelerators.

Effects of neuropeptide F on regeneration in Girardia tigrina (Platyhelminthes).

The effects of neuropeptide F (NPF; from Moniezia expansa) on the regeneration of Girardia tigrina were studied. The animals were decapitated and incubated in water (control) or NPF. The dynamics of the proliferation of the neoblasts in the developing tissue were studied during the course of regeneration by monitoring the mitotic index (MI). The effects of incubation in FMRFamide and GYIRFamide on the MI were also tested. The course of cephalic regeneration was followed with in vivo computer-assisted morphometry for up to 7 days. The development of the regenerating nervous system and the musculature was visualised by immunostaining with a primary antiserum to the C-terminal decapeptide of NPF (YFAIIGRPRFa) and tetramethylrhodamine-isothiocyanate-conjugated phalloidin, which stains F-actin in muscle filaments. The study showed that NPF had a stimulatory effect on the mitotic activity of the neoblasts. FMRFamide and GYIRFamide did not have this effect. NPF also stimulated the growth of the regenerating head and the growing nervous system and musculature. NPF is postulated to have a morphogenetic action in the regenerating animals.

NO nerves and their targets in a tapeworm: An immunocytochemical study of cGMP in Hymenolepis diminuta.

We studied the pattern of cGMP immunostaining (IS) after stimulation with a nitric oxide donor in the presence of an inhibitor of phosphodiesterase in adult Hymenolepis diminuta. cGMP-IS was detected in the peripheral nervous system, especially in nerve fibres close to the body muscle fibres. cGMP-IS also occurred in terminals beneath the basal lamina of the tegument and between the muscle fibres of the suckers. The pattern of cGMP-IS was compared to that of 5-HT-IS and GYIRFamide-IS. TRITC-conjugated phalloidin was used to stain the musculature.