Real-World Evaluation of the Safety and Effectiveness of 2.3% Hypertonic Saline Soft Mist Spray for Sino-Nasal Symptoms.

Introduction and aims Mildly hypertonic saline is more effective in relieving symptoms of nasal congestion compared to placebo or isotonic saline. Recently, a unique device, delivering a soft mist of 2.3% hypertonic sea-salt saline (Nasoclear PureHaleTM; Zydus Healthcare Ltd., India) has been introduced in India. The device uses a power-less manual technique to release the saline as a soft mist at 1 ml/min. Methods This is a retrospective, multi-centric, single-arm study to evaluate the safety and effectiveness of 2.3% hypertonic sea-salt saline nasal irrigation delivered through a soft mist device in patients with sino-nasal symptoms. This is an analysis of data of 130 patients collected from the medical records of 11 practicing pediatricians across India. Results The mean age of the patients was 5.23 ± 4.24 years; 63 % were boys and 37% were girls (n = 130). The mean reduction in total nasal symptom score (TNSS) at follow-up from baseline was 6.28 ± 0.18 (median days = 7) (95% CI = 5.92 to 6.64; p<0.0001; mean TNSS at baseline = 7.75 ± 2.01, mean TNSS at follow-up = 1.47± 1.30). Out of 130 patients, 33 patients (25.3%) showed complete improvement in TNSS, 93 patients (71.5%) had ≥ 50% improvement in TNSS while 4 patients (3.07%) showed <50% improvement in TNSS. The effectiveness of the device was rated as excellent (75%-100% improvement) and very good (50%-75% improvement) in 41 and 74 patients, respectively. It was rated as very easy to use and easy to use by 62 patients and 57 patients, respectively. One hundred nineteen patients (91.5%) were compliant with the prescribed frequency of the device and 110 patients (84.6%) were compliant with the prescribed duration of use of the device. No serious adverse events were reported; two patients reported mild side effects - stinging and irritation of the throat. Conclusions The 2.3% hypertonic sea-salt saline nasal irrigation delivered through the soft mist device was found to be well-tolerated and effective in patients with sino-nasal symptoms in real-world clinical settings. Clinical trial number The clinical trial number of this study is CTRI/2022/07/043751.

Barbed Suspension Bridge Pharyngoplasty: Introducing a Novel Technique for Barbed Pharyngoplasty.

Surgical management of Obstructive Sleep Apnea (OSA) and Snoring has undergone many major and minor changes over a period of last decade. The most common surgical approach for OSA is uvulopalatopharyngoplasty (Stuck et al. in Sleep Med 50:152-165, 2018). The main goals of treatment of OSA are to decrease the risk of deleterious health effects and improve quality of sleep (Evans et al. in Otolaryngol Clin North Am 53: 319-328, 2020). Since bimanual surgical techniques in the depth of oral cavity have been tricky, search for a less demanding & easy to learn technique is always on. The surgical technique should also provide long term results with manageable complications. Barbed suture has been in sporadic use for the last decade amongst sleep apnea surgeons for its advantage of knotless application and distributed suture tension. However, the barbed suture which has been used is absorbable and is used only to close the surgical wound on the soft palate. In this paper we are describing our technique of using the 3-0 Polybutester non absorbable barbed suture to perform a novel technique of palatal surgery, in which we suspend the lower part of the soft palate permanently as a suspension bridge between the right and left Pterygomandibular raphae, so that the lower part of the soft palate cannot move posteriorly to touch the posterior pharyngeal wall preventing airway obstruction whereas it can still move superiorly freely while swallowing or during phonation. This technique can prove to be a technically less demanding one which provides excellent long-term results in snoring and OSA with manageable complications.

Pulmonary Artery Hypertension in Transfusion-Dependent Thalassemia.

OBJECTIVE: Patients with transfusion-dependent thalassemia (TDT) are at risk of developing pulmonary artery hypertension (PAH) due to chronic hemolysis, iron overload, hypercoagulability and splenectomy. The objective of the study was to assess the prevalence and predictors of PAH in patients with TDT. METHODS: Patients aged 6-18 years with TDT were included. 2D-echocardiography was done to measure the pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF). T2* MRI was done to evaluate cardiac iron overload. N-terminal-pro brain natriuretic peptide (NT-pro BNP) level was also assessed. RESULTS: Out of 61 participants, PAH was noted in 19 (31.6%). Mean (SD) age of the patients with PAH and without PAH was 12.2 (3.8) and 9.6 (3.5) years, respectively (P = 0.016). Five of 19 patients with PAH (26.3%) had undergone splenectomy as against 5 of 41 patients without PAH (12.2%) (P = 0.17). Years since splenectomy was higher in the PAH group. Mean (SD) NT-Pro BNP levels were also higher in patients with PAH [63.80 (25.89) vs 41.97 (23.95), P = 0.01]. Significantly higher number of patients with PAH had cardiac T2* value of < 10 ms (P = 0.04). Age (OR 4.11; 95% CI 1.46-8.77), years since splenectomy (OR 3.24; 95% CI 1.30-7.86), NT-Pro BNP levels (OR 4.43; 95% CI 2.14-9.61) and cardiac T2* MRI (OR 2.46; 95% CI 2.18-6.90) values were predictors of PAH in patients with TDT. CONCLUSION: PAH was observed in 31.6% of patients, with older age and years since splenectomy being important risk factors. NT-Pro BNP can be used as screening test for detecting PAH.

Improving the Quality of Life in the Management of Allergic Rhinitis: New Perspective on Cetirizine.

BACKGROUND: Allergic rhinitis (AR) is associated with disturbed sleep and subsequent functioning, and an impaired quality of life (QoL). The symptoms of AR exhibit prominent circadian variations, with symptoms being more common at the night-time or early morning. Addressing these allergy-related sleep issues, impaired QoL, and circadian variation in symptoms is important from the patient perspective and should be considered in the management of AR. OBJECTIVE: To review the efficacy of cetirizine, a second-generation antihistamine and selective H1-receptor antagonist, in relation to improvement in the QoL of the patients, addressing the sleep disturbances and circadian variations in the symptoms of AR in clinical practice, and establishing its role as a contemporary antihistamine for the management of AR compared to newer antihistamines. METHODS: Systematic literature review of the databases such as PubMed/MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials from 1990 to 2020. RESULTS: The symptoms of AR exhibited a circadian variation, with symptoms being worse during the night and early morning. The patients with AR encountered several sleep-related symptoms, including poor sleep quality, daytime somnolence, fatigue, and impaired productivity and QoL. Impaired QoL in AR was related to the disease severity. Administration of cetirizine at bedtime provides effective control of sleep impairment and symptoms of AR, besides improving the QoL. The efficacy of cetirizine has been demonstrated to be superior or comparable to the newer second-generation antihistamines. Cetirizine exhibits a tolerability profile comparable to the newer antihistamines. CONCLUSION: With long years of clinical experience and a good tolerability profile, cetirizine represents a valuable therapeutic option for the management of AR, even 30 years after its introduction. Cetirizine is included in the National List of Essential Medicines of India for the management of allergic disorders in view of its established efficacy and safety profile as well as being a cost-effective option.

Noncanonical Sonic Hedgehog signaling amplifies platelet reactivity and thrombogenicity.

Sonic Hedgehog (Shh) is a morphogen in vertebrate embryos that is also associated with organ homeostasis in adults. We report here that human platelets, though enucleate, synthesize Shh from preexisting mRNAs upon agonist stimulation, and mobilize it for surface expression and release on extracellular vesicles, thus alluding to its putative role in platelet activation. Shh, in turn, induced a wave of noncanonical signaling in platelets leading to activation of small GTPase Ras homolog family member A and phosphorylation of myosin light chain in activated protein kinase-dependent manner. Remarkably, agonist-induced thrombogenic responses in platelets, which include platelet aggregation, granule secretion, and spreading on immobilized fibrinogen, were significantly attenuated by inhibition of Hedgehog signaling, thus, implicating inputs from Shh in potentiation of agonist-mediated platelet activation. In consistence, inhibition of the Shh pathway significantly impaired arterial thrombosis in mice. Taken together, the above observations strongly support a feed-forward loop of platelet stimulation triggered locally by Shh, similar to ADP and thromboxane A2, that contributes significantly to the stability of occlusive arterial thrombus and that can be investigated as a potential therapeutic target in thrombotic disorders.

Comparison of the effects of calcium channel blockers plus iron chelation therapy versus chelation therapy only on iron overload in children and young adults with transfusion-dependent thalassemia: A randomized double-blind placebo-controlled trial.

BACKGROUND: Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS: Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS: In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION: Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.

Geochemical controls on CO2 interactions with deep subsurface shales: implications for geologic carbon sequestration.

One of the primary drivers of global warming is the exponential increase in CO2 emissions. According to IPCC, if the CO2 emissions continue to increase at the current rate, global warming is likely to increase by 1.5 °C, above pre-industrial levels, between the years 2030 and 2052. Efficient and sustainable geologic CO2 sequestration (GCS) offers one plausible solution for reducing CO2 levels. The impermeable shale formations have traditionally served as good seals for reservoirs in which CO2 has been injected for GCS. The rapid development of subsurface organic-rich shales for hydrocarbon recovery has opened up the possibility of utilizing these hydraulically fractured shale reservoirs as potential target reservoirs for GCS. However, to evaluate the GCS potential of different types of shales, we need to better understand the geochemical reactions at CO2-fluid-shale interfaces and how they affect the flow and CO2 storage permanence. In this review, we discuss the current state of knowledge on the interactions of CO2 with shale fluids, minerals, and organic matter, and the impact of parameters such as pressure, temperature, and moisture content on these interactions. We also discuss the potential of using CO2 as an alternate fracturing fluid, its role in enhanced shale gas recovery, and different geochemical tracers to identify whether CO2 or brine migration occurred along a particular fluid transport pathway. Additionally, this review highlights the need for future studies to focus on determining (1) the contribution of CO2 solubility and the impact of formation water chemistry on GCS, (2) the rates of dissolution/precipitation and sorption reactions, (3) the role of mineralogical and structural heterogeneities in shale, (4) differences in reaction mechanisms/rates between gaseous CO2vs. brine mixed CO2vs. supercritical CO2, (5) the use of CO2 as a fracturing fluid and its proppant carrying capacity and (6) the role of CO2 in enhanced hydrocarbon recovery.

Unilateral Basal Ganglia Hyperintensity Secondary to Venous Congestion in a Case of Indirect Carotico-cavernous Fistula.

Intraparenchymal venous congestive changes secondary to carotico-cavernous fistula are not common. Isolated basal ganglia venous congestive changes in carotico-cavernous fistula have been rarely described. We report MRI findings of the unilateral basal ganglia hyperintensity, angiographic features including cortical venous reflux into a variant basal vein of Rosenthal, in a postpartum woman presenting with the left eye proptosis and the right upper limb weakness. We also describe the reversal of imaging findings and resolution of patients' symptoms after definitive treatment of the carotico-cavernous fistula by endovascular embolization.

Effect of ivabradine on heart rate, functional capacity and pulmonary artery pressure in patients of COPD with cor pulmonale.

We studied the effects of heart rate reduction by ivabradine to the ongoing therapy in patients with chronic obstructive pulmonary disease (COPD) and cor pulmonale.100 patients of COPD with cor pulmonale with sinus heart rate ≥ 90 bpm were randomly assigned to either ivabradine 5 mg twice daily (50 patients) or placebo (50 patients) alongwith standard therapy. Assessment was done at baseline and after 6 months which included 6 min walk test (6MWT), dyspnea scoring by modified borg scale, Lung function test by forced expiratory volume in 1 s (FEV1) and pulmonary artery systolic pressure (PASP) by echocardiogram. The drug group showed a significant reduction in heart rate from 95.1 ± 8.2 bpm to 71.1 ± 6.2 bpm (p < 0.001). This group also showed significant improvement in 6-min walk distance and dyspnea on modified Borg scale (p < 0.001) at 6 months follow up. However no significant difference was found between both groups regarding PASP or FEV1 at 6 months.

Design and evaluation of microemulsion-based efinaconazole formulations for targeted treatment of onychomycosis through transungual route: Ex vivo and nail clipping studies.

The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul® MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol® (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol® P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudo-ternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol® 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36±12.90µgcm-2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.

Understanding controls on the geochemistry of hydrocarbon produced waters from different basins across the US.

The most massive waste stream generated by conventional and unconventional hydrocarbon exploration is the produced water (PW). The costs and environmental issues associated with the management and disposal of PW, which contains high concentrations of inorganic and organic pollutants, is one of the most challenging problems faced by the oil and gas industry. Many of the current strategies for the reuse and recycling of PW are inefficient because of varying water demand and the spatial and temporal variations in the chemical composition of PW. The chemical composition of PW is controlled by a multitude of factors and can vary significantly over time. This study aims to understand different parameters and processes that control the quality of PW generated from hydrocarbon-bearing formations by analyzing relationships between their major ion concentrations, O, H, and Sr isotopic composition. We selected PW data sets from three conventional (Trenton, Edwards, and Wilcox Formations) and four unconventional (Lance, Marcellus, Bakken, and Mesaverde Formations) oil and gas formations with varying lithology and depositional environment. Using comparative geochemical data analysis, we determined that the geochemical signature of PW is controlled by a complex interplay of several factors, including the original source of water (connate marine vs. non-marine), migration of the basinal fluids, the nature and degree of water-mineral-hydrocarbon interactions, water recharge, processes such as evaporation and ultrafiltration, and production techniques (conventional vs. unconventional). The development of efficient PW recycle and reuse strategies requires a holistic understanding of the geological and hydrological history of each formation to account for the temporal and spatial heterogeneities.

Intraoperative Transcranial Embolization following Decompressive Craniectomy for a Dural Arteriovenous Fistula Presenting with Acutely Raised Intracranial Pressure.

We report the clinical details, imaging findings, and management of a 58-year-old female who presented with rapidly deteriorating neurological function and acute raise in intracranial pressure secondary to posterior fossa dural arteriovenous fistula (DAVF). In this report, we present the emergency management of the DAVF with single-stage combined surgical decompressive craniotomy and direct transcranial embolization.

Long-term Complications of Palate Surgery: A Multicenter Study of 217 Patients.

OBJECTIVES/HYPOTHESIS: To investigate long-term complications of newer reconstructive palate surgery techniques. STUDY DESIGN: Retrospective case-series analysis. METHODS: Retrospective six-country clinical study of OSA patients who had nose and palate surgery. RESULTS: There were 217 patients, mean age = 43.9 ± 12.5 years, mean body mass index = 25.9 ± 4.7, mean preoperative apnea-hypopnea index [AHI] = 30.5 ± 19.1, follow-up 41.3 months. A total of 217 palatal procedures were performed, including 50 expansion sphincter pharyngoplasties (ESP), 34 functional expansion pharyngoplasties (FEP), 40 barbed reposition pharyngoplasties (BRP), 64 modified uvulopalatopharyngoplasties (mUPPP), 11 uvulopalatal flap procedures (UPF), nine suspension pharyngoplasties (SP), eight relocation pharyngoplasties (RP), and one z-pharyngoplasty (ZPP). Complications included were constant and/or felt twice per week; dry throat (7.8%), throat lump feeling (11.5%), throat phlegm (10.1%), throat scar feeling (3.7%), and difficulty swallowing (0.5%). Of the 17 patients who had a dry throat complaint, two were constant (one SP, one RP), 15 were occasional (10 mUPPP, three SP, two BRP). Of the 25 patients with the throat lump feeling, four were constant (three RP, one ZPP), 21 were occasional (10 mUPPP, five SP, five UPF, one BRP). Of the 22 patients with the throat phlegm feeling, four were constant (two SP, two RP), 18 were occasional (10 mUPPP, four BRP, two FEP, two SP). Of the eight patients with throat scar feeling, eight were occasional (four SP, two mUPPP, one FEP, one RP), none were constant. One patient had difficulty swallowing (RP procedure). There was no velopharyngeal incompetence, taste disturbance, nor voice change. Highest symptom complaints were mUPPP, SP, and RP, whereas the lowest symptom complaint was ESP. CONCLUSIONS: Newer palatal techniques have shown to have less long-term complications compared to the older ablative techniques. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2281-2284, 2020.

Correction: Effect of maturity and mineralogy on fluid-rock reactions in the Marcellus Shale.

Correction for 'Effect of maturity and mineralogy on fluid-rock reactions in the Marcellus Shale' by John Pilewski et al., Environ. Sci.: Processes Impacts, 2019, DOI: 10.1039/c8em00452h.

Effect of maturity and mineralogy on fluid-rock reactions in the Marcellus Shale.

Natural gas extraction from the Appalachian Basin has significantly increased in the past decade. The push to properly dispose, reuse, or recycle the large amounts of produced fluids associated with hydraulic fracturing operations and design better fracturing fluids has necessitated a better understanding of the subsurface chemical reactions taking place during hydrocarbon extraction. Using autoclave reactors, this study mimics the conditions of deep subsurface shale reservoirs to observe the chemical evolution of fluids during the shut-in phase of hydraulic fracturing (HF), a period when hydraulic fracturing fluids (HFFs) remain confined in the reservoir. The experiment was conducted by combining a synthetic hydraulic fracturing fluid and powdered shale core samples in high temperature/pressure static autoclave reactors for 14 days. Shale samples of varying maturity and mineralogy were used to assess the effect of these variations on the proliferation of inorganic ions and low molecular weight volatile organic compounds (VOCs), mainly benzene, toluene, ethylbenzene and xylenes (BTEX) and monosubstituted carboxylic acids. Ion chromatography results indicate that the relative abundance of ions present was similar to that of water produced from HF operations in the Marcellus Shale basin. There was an increase of SO42- and PO43- and a decrease in Ba2+ upon fluid-shale reaction. Major ionic shifts indicate calcite dissolution in two of the fluid-shale reactions and barite precipitation in all fluid-shale reactions. Toluene, xylene, and carboxylic acids were produced in the shale-free control experiment. The most substantial increase in BTEX analytes was observed in reactions with low maturity shale, while the high maturity shale reaction produced no measurable BTEX compounds. Total organic carbon decreased in all reactions including fracturing fluid and shale, suggesting adsorption onto the organic matter (OM) matrix. The results from this study highlight that both the nature of OM and mineralogy play a key role in determining the fate of inorganic and organic compounds during fluid-shale interactions in the subsurface shale reservoir. Overall this study aims to contribute to the growing understanding of complex chemical interactions that occur in the shale reservoirs during HF, which is vital for determining the potential environmental impacts of HF and designing more efficient HFF and produced water recycling techniques for environmentally conscious natural gas production.

A Novel Grading System for Salpingopharyngeal Fold Hypertrophy in Obstructive Sleep Apnoea.

The present study aimed at reporting the incidence of Salpingopharyngeal Fold (SPF) hypertrophy on Drug Induced Sleep Endoscopy (DISE) in patients with Obstructive Sleep Apnoea (OSA, validate a grading system and analyse the impact of various grades on the clinical presentation while ascertaining its relation with Apnoea-Hypopnoea Index (AHI). A retrospective analysis of 169 patients with polysomnographic confirmation of obstructive sleep apnoea has been done in the study. The DISE video data of 169 patients was evaluated by two ENT surgeons individually and they graded the hypertrophy of the fold as Grade 0 being normal anatomy, Grade 1 being hypertrophy causing partial obstruction and Grade 2 being hypertrophy causing complete obstruction of lateral pharyngeal wall. It was found that the presence of SPF hypertrophy independently adds considerably to the severity of the obstruction, attributing to lateral collapse at the upper retropalatal level and also significantly increases AHI. It is thus advised to consider the grade of SPF hypertrophy while surgically planning the management of patients with OSA.

Anatomic and Pathophysiologic Considerations in Surgical Treatment of Obstructive Sleep Apnea.

Evaluation of the upper airway is key for a successful surgical management. Proper evaluation can be done only with a good understanding of the anatomy and pathophysiology of the upper airway. The authors discuss surgical anatomy from a soft tissue and bony perspective in detail along with its clinical implications. The complex interaction among pharyngeal dilator tone, arousal threshold, respiratory control instability, and changes in lung volume during sleep play an important role in obstructive sleep apnea. Because all the anatomic and physiologic characteristics discussed have genetic predisposition, gene therapy may play a pivotal role in the future.

Minimax c th percentile of makespan in surgical scheduling.

In this paper, we address the problem of finding an assignment of n surgeries to be performed in one of m parallel identical operating rooms (ORs), given each surgery has a stochastic duration with a known mean and standard deviation. The objective is to minimise the maximum of the cth percentile of makespan of any OR. We formulate this problem as a nonlinear integer program, and small-sized instances are solved using the GAMS BONMIN solver. We develop a greedy heuristic and a genetic algorithm procedure for solving large-sized instances. Using real data from a major U.S. teaching hospital and benchmarking datasets from the literature, we report on the performance of the heuristics as compared to the GAMS BONMIN solver.

Improved Kerogen Models for Determining Thermal Maturity and Hydrocarbon Potential of Shale.

Kerogen is the insoluble component of organic-rich shales that controls the type and amount of hydrocarbons generated in conventional and unconventional reservoirs. Significant progress has recently been made in developing structural models of kerogen. However, there is still a large gap in understanding the evolution of the molecular components of kerogen with thermal maturation and their hydrocarbon (HC) generative potential. Here, we determine the variations in different molecular fragments of kerogen from a Marcellus Shale maturity series (with VRo ranging from 0.8 to 3) using quantitative 13C MultiCP/MAS NMR and MultiCP NMR/DD (dipolar dephasing). These molecular variations provide insight into the (1) evolution of the molecular structure of kerogen with increasing thermal maturity and, (2) the primary molecular contributors to HC generation. Our results also indicate that old model equations based on structural parameters of kerogen underestimate the thermal maturity and overestimate the HC generation potential of Marcellus Shale samples. This could primarily be due to the fact that the kerogen samples used to reconstruct old models were mostly derived from immature shales (VRo <1) acquired from different basins with varying depositional environments. We utilized the kerogen molecular parameters determined from the Marcellus maturity series samples to develop improved models for determining thermal maturity and HC potential of Marcellus Shale. The models generated in this study could also potentially be applied to other shales of similar maturity range and paleo-depositional environments.

Familial hypercholesterolemia supravalvular aortic stenosis and extensive atherosclerosis.

Familial hypercholesterolemia is an autosomally dominant disorder caused by various mutations in low-density lipoprotein receptor genes. This can lead to premature coronary atherosclerosis and cardiac-related death. The symptoms are more severe in the homozygous type of the disease. Premature malignant atherogenesis leading to aortic root abnormalities causing supravalvular aortic stenosis is rare. Our case demonstrates the diagnostic imaging findings of the phenotype of patients who have severe elevated LDL with familial hypercolesterolemia.