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Background: Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. Objective: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for of MH susceptible patients. Methods: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. Results: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P <  0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P <  0.001) were significantly higher compared to 0, indicating hypertrophy. Conclusions: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.

New applications on memory and logic devices need to form line shape pattern below 20 nm. Most of the prior articles for studying HSQ line CD resolution applied hot or cold (non-room temperature (RT)) development, salty development, KOH-based development or high concentration TMAH developer (like 25%) to push CD resolution to below 10 nm but these methods are not standard IC process compatible with 2.38% TMAH development at RT. E-beam lithography processes are applied to investigate CD resolution on RRAM film stacking of TiN/Ti/HfOx with or without proximity effect correction (PEC). Both dose and shape (line CD and pitch) modulations are applied in this study to obtain finest line width resolution using IC process compatible 2.38% TMAH developer at RT. Experimental results are summarized below. Lowest base dose of HSQ for pattern to be resolvable is larger than 1,000 (μC/cm 2 ). Smallest line CD of 13.1 nm for designed CD of 5 nm (G4) is resolved to 2 separate lines on R1st dense-line pattern with e-beam dose of 5,000 (μC/cm 2 ) assisted by dose PEC. Two lines of R1st dense-pattern is merged to single line of 14.7 nm at 10,000 (μC/cm 2 ). 2lines dense-line pattern is clearly resolved to 2 separate lines at 1,500 (μC/cm 2 ) but merged to one line at 2,000 (μC/cm 2 ). Iso-line on the right of two dense-lines of 2lines pattern contributes backscattered dose which increases the line width. 5lines dense-line pattern could only resolve to 18.3 nm. Iso-line R1st_1L is resolvable to 18.5 nm with uniform distribution of CD across the line and 13.6 nm is also resolved with more rough line edge. In summary, sub-14 nm line width of HSQ could be resolved by the combination of e-beam dose and shape modulations using standard 2.38% TAMH developer. This process is suitable for applications using metal oxide films.