Design of the first fusion experiment to achieve target energy gain G>1.

In this work we present the design of the first controlled fusion laboratory experiment to reach target gain G>1 N221204 (5 December 2022) [Phys. Rev. Lett. 132, 065102 (2024)10.1103/PhysRevLett.132.065102], performed at the National Ignition Facility, where the fusion energy produced (3.15 MJ) exceeded the amount of laser energy required to drive the target (2.05 MJ). Following the demonstration of ignition according to the Lawson criterion N210808, experiments were impacted by nonideal experimental fielding conditions, such as increased (known) target defects that seeded hydrodynamic instabilities or unintentional low-mode asymmetries from nonuniformities in the target or laser delivery, which led to reduced fusion yields less than 1 MJ. This Letter details design changes, including using an extended higher-energy laser pulse to drive a thicker high-density carbon (also known as diamond) capsule, that led to increased fusion energy output compared to N210808 as well as improved robustness for achieving high fusion energies (greater than 1 MJ) in the presence of significant low-mode asymmetries. For this design, the burnup fraction of the deuterium and tritium (DT) fuel was increased (approximately 4% fuel burnup and a target gain of approximately 1.5 compared to approximately 2% fuel burnup and target gain approximately 0.7 for N210808) as a result of increased total (DT plus capsule) areal density at maximum compression compared to N210808. Radiation-hydrodynamic simulations of this design predicted achieving target gain greater than 1 and also the magnitude of increase in fusion energy produced compared to N210808. The plasma conditions and hotspot power balance (fusion power produced vs input power and power losses) using these simulations are presented. Since the drafting of this manuscript, the results of this paper have been replicated and exceeded (N230729) in this design, together with a higher-quality diamond capsule, setting a new record of approximately 3.88MJ of fusion energy and fusion energy target gain of approximately 1.9.

Simultaneous visualization of wall motion, beam propagation, and implosion symmetry on the National Ignition Facility (invited).

Achieving a symmetric implosion in National Ignition Facility indirect drive targets requires understanding and control of dynamic changes to the laser power transport in the hohlraum. We developed a new experimental platform to simultaneously visualize wall-plasma motion and dynamic laser power transport in the hohlraum and are using it to investigate correlations of these measurements with the imploded capsule symmetry. In a series of experiments where we made one single parameter variation, we show the value of this new platform in developing an understanding of laser transport and implosion symmetry. This platform also provides a new way to evaluate dynamic performance of advanced hohlraum designs.

Mechanics of particulate composites with glassy polymer binders in compression.

Whether used as structural components in design or matrix materials for composites, the mechanical properties of polymers are increasingly important. The compressive response of extruded polymethyl methacrylate (PMMA) rod with aligned polymer chains and Al-Ni-PMMA particulate composites are investigated across a range of strain rates and temperatures. The particulate composites were prepared using an injection-moulding technique resulting in highly anisotropic microstructures. The mechanics of these materials are discussed in the light of theories of deformation for glassy polymers. The experimental data from this study are compared with PMMA results from the literature as well as epoxy-based composites with identical particulates. The PMMA exhibited the expected strain rate and temperature dependence and brittle failure was observed at the highest strain rates and lowest temperatures. The Al-Ni-PMMA composites were found to have similar stress-strain response to the PMMA with reduced strain softening after yield. Increasing volume fraction of particulates in the composite resulted in decreased strength.

Coblation for epistaxis management in patients with hereditary haemorrhagic telangiectasia: a multicentre case series.

OBJECTIVE: To propose radiofrequency coblation as a potential treatment modality for mild to moderate epistaxis in patients with hereditary haemorrhagic telangiectasia. METHOD: Case reports and review of the world literature concerning coblation and other treatment modalities for epistaxis in patients with hereditary haemorrhagic telangiectasia. RESULTS: Effective epistaxis control was achieved in four out of five cases of hereditary haemorrhagic telangiectasia. In the fifth case, we struggled to achieve haemostasis due to disease severity. CONCLUSION: Radiofrequency coblation is a novel technique, which was found to be a safe, effective, quick and well tolerated treatment option for epistaxis management in patients with hereditary haemorrhagic telangiectasia.

Endoscopic resection of intracranial dermoid cysts.

INTRODUCTION: Nasal dermoid cysts are congenital lesions which are often diagnosed in infancy or childhood. However, a small number present in adulthood, and some extend intracranially. Traditional treatment for the intracranial portion of these cysts includes frontal craniotomy. CASE REPORTS: Two intracranial dermoid cysts were resected via a transnasal endoscopic approach, using 70° nasal endoscopy for complete visualisation and intracranial tumour removal. We describe our technique for the procedure itself and for reconstruction of the skull base defect. DISCUSSION AND CONCLUSION: The endoscopic transnasal skull base approach is an excellent alternative to a traditional frontal craniotomy, to achieve complete resection of intracranial dermoid cysts.

DeltaF508 CFTR processing correction and activity in polarized airway and non-airway cell monolayers.

We examined the activity of DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) stably expressed in polarized cystic fibrosis bronchial epithelial cells (CFBE41o(-)) human airway cells and Fisher Rat Thyroid (FRT) cells following treatment with low temperature and a panel of small molecule correctors of DeltaF508 CFTR misprocessing. Corr-4a increased DeltaF508 CFTR-dependent Cl(-) conductance in both cell types, whereas treatment with VRT-325 or VRT-640 increased activity only in FRT cells. Total currents stimulated by forskolin and genistein demonstrated similar dose/response effects to Corr-4a treatment in each cell type. When examining the relative contribution of forskolin and genistein to total stimulated current, CFBE41o(-) cells had smaller forskolin-stimulated I(sc) following either low temperature or corr-4a treatment (10-30% of the total I(sc) produced by the combination of both CFTR agonists). In contrast, forskolin consistently contributed greater than 40% of total I(sc) in DeltaF508 CFTR-expressing FRT cells corrected with low temperature, and corr-4a treatment preferentially enhanced forskolin dependent currents only in FRT cells (60% of total I(sc)). DeltaF508 CFTR cDNA transcript levels, DeltaF508 CFTR C band levels, or cAMP signaling did not account for the reduced forskolin response in CFBE41o(-) cells. Treatment with non-specific inhibitors of phosphodiesterases (papaverine) or phosphatases (endothall) did not restore DeltaF508 CFTR activation by forskolin in CFBE41o(-) cells, indicating that the Cl(-) transport defect in airway cells is distal to cAMP or its metabolism. The results identify important differences in DeltaF508 CFTR activation in polarizing epithelial models of CF, and have important implications regarding detection of rescued of DeltaF508 CFTR in vivo.

Frontal recess cells: a rare cause of frontal sinus pneumocoele.

BACKGROUND AND AIMS: A pneumocoele is a pathologically expanding, air-containing paranasal sinus. Pneumocoeles are uncommon entities, with very few cases reported in the literature. The most plausible aetiological theory is that of a one-way valve effect allowing air into the sinus under increased pressure without pressure equilibration. METHODS: Review of a frontal sinus pneumocoele caused by a type III frontal cell and intersinus septal cell. RESULTS: We present a patient with chronic sinusitis who developed a pneumocoele of her left frontal sinus with erosion into her orbit. This patient was a habitual, chronic nose-blower with a large type III frontal cell adjacent to an intersinus septal cell. CONCLUSION: We propose the new theory that, in our patient, such cells formed a one-way valve, causing air-trapping and pathological expansion of the frontal sinus. To our knowledge, there are no previously published cases that establish an association between large frontal cells and expansion of a pneumocoele.

Real-time computed tomography image update for endoscopic skull base surgery.

INTRODUCTION: The development of computer-aided systems for endoscopic sinus surgery has enabled surgical navigation through diseased or surgically altered sinus anatomy with increased confidence. However, conventional computer-aided systems do not provide intra-operative updated computed tomography imaging. We describe the technical aspects of the xCAT, a new intra-operative mobile volume computed tomography scanner. TECHNICAL REPORT: A patient with a malignant melanoma unwittingly removed at another hospital underwent surgery for removal of the lateral nasal wall and directed biopsies, in an attempt to identify the site of tumour origin. The procedure was performed with the GE InstaTrak 3500 Plus computer-aided system, updated with intra-operative computed tomography images. Intra-operative, updated images were integrated successfully into the InstaTrak system, and these images were consistent with the observed endoscopic anatomy. CONCLUSION: The xCAT intra-operative mobile volume computed tomography scanner is a technological advancement that can assist the endoscopic sinus surgeon when performing complex rhinological and skull base procedures.

Endoscopic repair of frontal sinus cerebrospinal fluid leaks.

OBJECTIVE: To describe endoscopic management of frontal sinus cerebrospinal fluid (CSF) leaks. STUDY DESIGN: Retrospective. METHODS: We reviewed all frontal sinus CSF leaks treated using an endoscopic approach at our institutions from 1998 to 2003. CSF leaks originated immediately adjacent to or within the frontal recess or frontal sinus proper for inclusion in the study. Data collected included demographics, presenting signs and symptoms, site and size of skull-base defect, surgical approach, repair technique, and clinical follow up. RESULTS: Seven frontal sinus CSF leaks in six patients were repaired endoscopically. Average age of presentation was 45 years (range 25-65 years). Aetiology was idiopathic (three), congenital (one), accidental trauma (one), and surgical trauma (two). All patients presented with CSF rhinorrhea; two patients presented with meningitis. Four defects originated in the frontal recess, while two others involved the posterior table and frontal sinus outflow tract. Four patients had associated encephaloceles. We performed endoscopic repair in all six patients with one patient requiring an adjuvant osteoplastic flap without obliteration. All repairs were successful at the first attempt with a mean follow up of 13 months. All frontal sinuses remained patent on both post-operative endoscopic and radiographic exam. CONCLUSIONS: Endoscopic repair of frontal sinus CSF leaks and encephaloceles can be an effective method if meticulous attention is directed toward preservation of the frontal sinus outflow tract, thus avoiding an osteoplastic flap and obliteration. The major limiting factor for an endoscopic approach is extreme extension superiorly or laterally within the posterior table beyond the reach of current instrumentation.

Telehealth and communication technologies in health: summary and action plan.

INTRODUCTION: Rapid innovations and improvements in communication technologies have opened many new channels for health education and delivery, as well as disaster management. Theme 2 examined the role and applicability of these technologies to Disaster Medicine and Management and the various issues involved in their use. METHODS: Details of the methods used are provided in the introductory paper. The chairs moderated all presentations and produced a summary that was presented to an assembly of all of the delegates. The chairs then presided over a workshop that resulted in the generation of a set Action Plans that then were reported to the collective group of all delegates. RESULTS: Main points developed during the presentations and discussion included harnessing convergence, seeking interoperability, building partnerships and making it appropriate. This group identified four Principles of Action underlying its plan: (1) investigate possibilities, (2) identify stakeholders, (3) invite participation, and (4) involve discussants in activities. DISCUSSION: Action plans were categorized into three areas that included "thinking globally, acting regionally", forming a telehealth advisory group, and increasing corporate partnerships. CONCLUSIONS: Technology is opening many opportunities that have applications in disaster management. To optimize benefits, goals and standards must be agreed upon and implemented.

Merkel cell carcinoma: an overview and case report.

Merkel cell carcinoma is an extremely rare neoplasm with a high rate of recurrence and metastasis. The lesions predominantly arise on sun-exposed areas of skin in whites between the sixth and seventh decades of life. Within the head and neck region, the cheeks and eyelids are the most common sites. This article outlines the etiology, pathogenesis, and treatment of this rare but highly aggressive tumor.

Meniere's disease.

Meniere's disease is an idiopathic disorder of the inner ear characterized by the syndrome of endolymphatic hydrops, episodic vertigo, fluctuating hearing loss, tinnitus, and aural fullness. People with this disorder may be severely disabled. Medical therapy exists in the form of diuretics and dietary restriction of salt to minimize the fluid pressure in the labyrinth and cochlea. Treatment of allergies with desensitization and steroids has also shown to be effective in selected patients. Surgical therapies exist in two categories, conservative and ablative. Endolymphatic sac decompression with or without shunt placement remains highly effective and we feel that it should be the first line surgical therapy for patients who fail medical therapy. Ablative therapies include labyrinthectomy (medical or surgical) and vestibular neurectomy. Both of these procedures control the episodic vertigo by destroying vestibular function in the affected ear and should be reserved for patients who have persistent vertigo in spite of more conservative treatments.

PH20: a novel tumor marker for laryngeal cancer.

OBJECTIVE: To determine whether levels of PH-20, a hyaluronidase similar to that found in human sperm, are elevated in laryngeal cancer tissue. DESIGN: In this case-control study. reverse transcription polymerase chain reaction was used to measure levels of PH-20 messenger RNA in tissue taken from laryngectomy specimens. SETTING: A university medical center. PATIENTS: We compared tissue samples taken from 11 patients with laryngeal cancer, and from 2 metastatic lymph nodes, with samples of normal, healthy laryngeal tissue and prostate cancer tissue (positive control). MAIN OUTCOME MEASURE: PH-20 complementary DNA expression as quantified by densitometric analysis. RESULTS: Expression of PH-20 was significantly higher in nonirradiated laryngeal cancer specimens than in normal laryngeal tissue (P<.01). Metastatic lymph nodes also had higher levels of PH-20 expression than did primary laryngeal cancer tissue (P = .11) and normal laryngeal tissue (P<.01). Irradiated laryngeal cancer specimens had PH-20 levels comparable to normal. CONCLUSIONS: We report the first data on PH-20 expression in laryngeal cancer tissue. PH-20 expression is significantly elevated in primary laryngeal cancer tissue and seems to be even higher in metastatic lesions compared with normal laryngeal tissue. PH-20 may be a useful tumor marker and prognostic tool for laryngeal cancer.

Amitriptyline treatment for severe recurrent idiopathic cystitis in cats.

OBJECTIVE: To evaluate the safety and efficacy of amitriptyline hydrochloride in the treatment of severe recurrent idiopathic cystitis (IC) in cats. DESIGN: Prospective study. ANIMALS: 15 cats with IC that failed to respond to other treatments. PROCEDURE: Each cat received 10 mg of amitriptyline, PO, every 24 hours in the evening for 12 months or until signs recurred. Urinalysis, CBC, serum biochemical analysis, urine bacteriologic culture, and cystoscopy were performed initially, and after 6 and 12 months in responders. Severity scores of owner-observed signs of lower urinary tract (bladder and urethra) disease were recorded. RESULTS: During the first 6 months of treatment, 11 of the 15 cats had no owner-observed signs of lower urinary tract disease. During the next 6 months, 9 of 15 cats remained free of signs of cystitis. Despite clinical improvement, cystoscopic abnormalities persisted in all cats at the 6- and 12-month evaluations. Hematuria and proteinuria were decreased at the 12-month evaluation compared with the initial evaluation. Two of 15 cats initially appeared somnolent after amitriptyline treatment. Of 9 cats completing the study, 7 had increased body weight and 8 had decreased coat quality compared with the initial evaluations. Four cats developed small cystic calculi during the first 6 months of the study. Serum biochemical or hematologic abnormalities were not detected during the study. CLINICAL IMPLICATIONS: Amitriptyline treatment successfully decreased clinical signs of severe recurrent IC in 9 of 15 cats treated. Somnolence, weight gain, decreased grooming, and transient cystic calculi were observed during treatment in some cats.

Excretion of fluorescein in the urine of women with interstitial cystitis.

PURPOSE: Altered bladder permeability may have a role in the pathogenesis of interstitial cystitis. Fluorescein, a fluorescent dye of molecular weight 325, has been used to assess membrane permeability. Orally ingested fluorescein normally is rapidly conjugated to glucuronate by the liver and excreted in the urine. MATERIALS AND METHODS: To test its use as a marker of bladder permeability, we administered fluorescein orally to 6 patients with interstitial cystitis who satisfied National Institutes of Health, National Institute for Diabetes and Digestive and Kidney Diseases criteria and to 6 normal female control subjects. After emptying the bladder and collection of a baseline blood sample, fasted subjects ingested 20 mg. fluorescein and blood samples were collected 1, 2, 3, 4 and 24 hours later. Urine was collected during each of the first 4 hours, and then from 4 to 10, 10 to 16 and 16 to 24 hours. Urine volume was measured, and all plasma and urine samples were analyzed for fluorescein. RESULTS: Plasma fluorescein concentrations (ng./ml.) were significantly (p < 0.05) higher in interstitial cystitis patients than in control subjects at 1 and 2 hours after fluorescein ingestion. Urine fluorescein excretion (mg.) was significantly (p < 0.05) lower in interstitial cystitis patients than in control subjects at 4 to 10 hours after fluorescein ingestion, and for the entire 24 hours. CONCLUSIONS: The increased fluorescein concentration in the plasma and decreased excretion in the urine of interstitial cystitis patients suggest that fluorescein may be a useful marker of altered membrane permeability.

Clinical evaluation of cats with nonobstructive urinary tract diseases.

OBJECTIVE: To identify the underlying cause of clinical signs in cats with nonobstructive diseases of the bladder and urethra. DESIGN: Prospective case series. SAMPLE POPULATION: 109 cats examined by the urology service of The Ohio State University's veterinary teaching hospital because of stranguria, hematuria, pollakiuria, or urination in inappropriate locations. PROCEDURE: History was obtained and a CBC, serum biochemical analyses, serologic tests for FeLV and feline immunodeficiency virus, urinalysis, bacterial culture of urine, and contrast radiography or urethrocystoscopy (females only) were performed. RESULTS: 16 cats had cystic calculi: 8 had struvite uroliths, 7 had calcium oxalate uroliths, and 1 had a urolith of unknown composition in conjunction with an anatomic defect. Anatomic defects, including diverticulae, urethral strictures, and a malpositioned urethra, were identified in 12 cats. A urinary tract infection was identified in 1 cat, and neoplasia was diagnosed in 2. One of the cats with neoplasia also had a struvite urolith. The remaining 80 cats did not have an anatomic defect, urolith, or tumor. Ten of these cats also did not have radiographic or cystoscopic abnormalities and were presumed to have a behavioral disorder. The remaining 70 cats had radiographic or cystoscopic abnormalities, and idiopathic cystitis was diagnosed. In 14 of the cats with idiopathic cystitis, results of a urinalysis were normal. Cats with idiopathic cystitis were significantly more likely to eat dry food exclusively (59%) than were cats in the general population (19%). CLINICAL IMPLICATIONS: Results suggest that idiopathic cystitis occurs commonly in cats with stranguria, hematuria, pollakiuria, or inappropriate elimination and is associated with consumption of dry foods. Contrast radiography or cystoscopy is necessary for differentiating idiopathic cystitis from behavioral disorders in some cats.

Decreased urine glycosaminoglycan excretion in cats with interstitial cystitis.

PURPOSE: The urine protein and glycosaminoglycan (GAG) excretion of normal cats was compared with that of cats suffering from interstitial cystitis (IC), which is reported to decrease urine GAG excretion in humans. MATERIALS AND METHODS: Total urine GAG concentration was measured in random and 24-hour urine specimens by spectrophotometry by 1,9-dimethylmethylene blue (DMB) chloride. RESULTS: In both random and 24-hour urine samples, GAG and protein concentrations and GAG:creatinine and protein:creatinine ratios all were significantly lower in cats with IC. Total GAG and protein excretion also were significantly lower in 24-hour urine samples from cats with IC. CONCLUSIONS: GAG excretion was decreased in cats with IC, as it is in humans. It is unclear whether this is due to changes in synthesis, metabolism, or bladder permeability.