Harnessing entropic and enthalpic contributions to create a negative tone chemically amplified molecular resist for high-resolution lithography.

Here we present a new resist design concept. By adding dilute cross-linkers to a chemically amplified molecular resist, we synergize entropic and enthalpic contributions to dissolution by harnessing both changes to molecular weight and changes in intermolecular bonding to create a system that outperforms resists that emphasize one contribution over the other. We study patterning performance, resist modulus, solubility kinetics and material redistribution as a function of cross-linker concentration. Cross-linking varies from dilute oligomerization to creating a highly networked system. The addition of small amounts of cross-linker improves resist performance by reducing material diffusion and redistribution during development and stiffening the features to avoid pattern collapse. The new dilute cross-linking system achieves the highest resolution of a sensitive molecular glass resist at 20 nm half-pitch and line-edge roughness (LER) of 4.3 nm and can inform new resist design towards patterned feature control at the molecular level.

Effect of canagliflozin on the decline of estimated glomerular filtration rate in chronic kidney disease patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III study in Japan.

AIMS/INTRODUCTION: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial has shown the effects of canagliflozin on preventing clinically important kidney outcomes in patients with type 2 diabetes mellitus and chronic kidney disease; however, not many Japanese patients were included in the trial. The present study evaluated the efficacy and safety of canagliflozin in Japanese chronic kidney disease patients with type 2 diabetes mellitus. MATERIALS AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III study, chronic kidney disease patients with type 2 diabetes mellitus were randomly assigned to receive either 100 mg canagliflozin or a matching placebo once daily for 104 weeks. The primary efficacy end-point was the incidence of a 30% decline in estimated glomerular filtration rate. RESULTS: Overall, 308 patients were randomized to the canagliflozin (n = 154) and placebo (n = 154) groups. The incidence of a 30% decline in estimated glomerular filtration rate at week 104 was 18.2% and 29.5%, respectively, and the point estimate of the intergroup difference (placebo - canagliflozin) was 11.3% (95% confidence interval 1.2-21.5, P = 0.029), which was significant. The overall incidence of adverse events was similar in the two groups. CONCLUSIONS: This study suggests that canagliflozin safely reduces the risk of end-stage renal disease in Japanese chronic kidney disease patients with type 2 diabetes mellitus.

An autopsy case of ornithine transcarbamylase deficiency.

We present an autopsy case of ornithine transcarbamylase (OTC) deficiency with grumose degeneration in the dentate nucleus of the cerebellum. The patient had intractable neonatal convulsions and hyperammonemia from the 3rd day after birth. Diagnosis of OTC deficiency was made based on null activity of the enzyme and four-base deletions in exon 9 of the OTC gene. Death was due to sepsis as well as disseminated intravascular coagulation at 1 year and 2 months of age. Neuropathology showed multiple cystic changes and ulegyria in the bilateral frontal and parietal lobes. Multiple cysts were associated with the region, which was infiltrated with macrophages surrounded by astroglia showing palisading pattern. Ferrugination was marked in the thalamus and severe neuronal loss with astrogliotic change in the CA1-2 area of the hippocampus. Grumose degeneration was noted in the dentate nucleus of the cerebellum. This is the first report of grumose degeneration in OTC deficiency.

[A case of resected spinal metastasis following colectomy and hepatectomy for descending colon carcinoma].

The patient was a 49-year-old man. In 1995, he underwent left hemicolectomy for descending colon carcinoma, and in 1996, partial hepatic resection was performed for liver metastasis. Post-operative chemotherapy was performed with 5'-DFUR. Five years later, he had lumbar and femoral pain. X-ray and MRI examination revealed a compression fracture and a spinal tumor at the XII thoracic vertebra. Though chemoradiotherapy was performed, the symptoms of pain, numbness and muscle weakness progressed. A resection of the metastatic spinal tumor was performed. Following several systemic chemotherapies, such as 5-FU/l-LV, CPT-11 + 5-FU/l-LV and low-dose CPT-11/UFT, radiotherapy was performed for the progressed bone tumor. At 2 years after surgery, he is still able to walk and no other site of recurrence has been detected.

[A case of lymph node metastasis after 7 years from Hartmann's operation for stage IV sigmoid colon carcinoma].

The case was a 49-year-old woman. In 1995, she underwent Hartmann's operation for sigmoid colon carcinoma. Histological stage was IV [se, n4(+), P0, H0, M(-)]. Adjuvant chemotherapy was performed by MMC and 5'-DFUR. After 7 years from the surgery, she had a lumbar pain. CT examination revealed a retroperitoneal tumor-like shadow and Para-aortic lymph nodes were swelling. In 2002, she underwent probe laparotomy. There were massive lymph nodes metastasis, and tumor resection was impossible. Following several systemic chemotherapies such as UFT/CPT-11 and TS-1, the tumor progressed and liver metastasis appeared. After 9 years from the first operation, she is still able to eat and her performance status is 1.

A case of Baraitser-Winter syndrome with unusual brain MRI findings: pachygyria, subcortical-band heterotopia, and periventricular heterotopia.

Baraitser-Winter syndrome (BaWS) is characterized by iris coloboma, ptosis, hypertelorism, and mental retardation; it is a rare multiple congenital anomaly or a mental-retardation syndrome of unknown etiology. Patients suffering from this syndrome have been also found to show brain anomalies such as pachygyria, subcortical-band heterotopia (SBH), and hippocampal malformations; therefore, these anomalies have been included in the phenotypic spectrum of this syndrome. We report the case of a Japanese boy suffering from BaWS; the patient's brain magnetic resonance imaging scan revealed pachygyria, SBH, and periventricular heterotopia. However, the results of the genome-wide array comparative genomic hybridization did not reveal any chromosomal rearrangements.

An infant with systemic hypertension, renal artery stenosis, and neuroblastoma.

A newborn girl with neuroblastoma presented with hypertension (blood pressure 200/140 mm Hg). The concentration of active renin in the ipsilateral renal vein was exceedingly high compared with those in the other venous systems, and angiography results showed narrowing of the contralateral 2 renal arteries. The tumor regressed in size after chemotherapy, but the blood pressure remained high. Percutaneous transluminal angioplasty (PTA) for the left renal arteries was performed twice, the first one at 5 months of age, which achieved some success in the recovery of impaired kidney function. At 8 months of age, she underwent radical resection of the neuroblastoma and removal of the right kidney, and the blood pressure promptly returned to normal postoperatively. The current patient represents the second youngest, well-documented case of renovascular hypertension with neuroblastoma in early infancy.