Tailored nanodiamonds for hyperpolarized ¹³C MRI

Nanodiamond is poised to become an attractive material for hyperpolarized ¹³C magnetic resonance imaging if large nuclear polarizations can be achieved without the accompanying rapid spin-relaxation driven by paramagnetic species. Here we report enhanced and long-lived ¹³C polarization in synthetic nanodiamonds tailored by acid-cleaning and air-oxidation protocols. Our results separate the contributions of different paramagnetic species on the polarization behavior, identifying the importance of substitutional nitrogen defect centers in the nanodiamond core. These results are likely of use in the development of nanodiamond-based imaging agents with size distributions of relevance for examining biological processes

Personal non-commercial use only

ABSTRACT. Objective. To put forward a new concept -Blau arteritis, a form of large-vessel vasculitis phenotypically related to Takayasu disease but genetically and clinically part of an expanded phenotype of Blau syndrome. Methods. We provide a clinical description of a new case and summarize previously published cases of arteritis associated with Blau syndrome. Genetic testing was performed by direct sequencing of exon 4 of the NOD2 gene. Results. The case described and those reviewed from the literature demonstrate the emerging phenotype of Takayasu-like arteritis in patients with Blau syndrome. Although most patients described to date depict an otherwise classic Blau syndrome phenotype, the current case was atypical in that the predominant features were arteritic. A novel substitution, G464W, in a highly conserved position near the nucleotide oligomerization domain of the NOD2 protein is also described. Blau syndrome is a monogenic granulomatous disease characterized in its most typical form by a triad of exuberant polyarthritis, uveitis, and granulomatous dermatitis 1 . It is caused by single amino acid substitutions at or near the NACHT domain of NOD2 2 . Although its systemic expression is well recognized after the descriptions of the expanded phenotype of Blau syndrome 3,4 , large-vessel vasculitis remains one of its serious and yet underrecognized manifestations if not actively sought by the treating physician. We describe an 8-year-old girl with symptomatic Takayasu-like arteritis and cardiomyopathy against the background of Blau syndrome with a G464W substitution in NOD2. We reported a similar case in 1989 5 , while others have observed arteritis among children with both sporadic and familial Blau phenotype before the mutation was known MATERIALS AND METHODS A girl, now 11 years old, from rural India, presented to us for the first time at 18 months of age, with bilateral knee effusions of a few months' duration in the absence of rash, uveitis, or systemic features. From the age of 1 month she had had recurrent and unexplained episodes of fever. Her antinuclear antibody result was negative. With a working diagnosis of oligoarticular juvenile arthritis she was administered intraarticular steroids, to which she responded well. She was lost to followup for almost 6 years thereafter. At the age of 8 years, she presented with gradually progressive dyspnea and palpitations of 3 months' duration. She had not thrived, and at this stage she weighed 17.2 kg and her height was 113 cm. There were no systemic features but joint examination showed "boggy synovitis" of the right elbow and knee. Cardiovascular examination showed an irregular pulse with a pulsatile precordium and evidence of congestive heart failure. A rhythm strip on electrocardiography showed ventricular extra beats. The echocardiogram revealed dilated ventricles, generalized hypokinesia with an ejection fraction of 20%, mild tricuspid and aortic regurgitation, and abnormal echogenicity within the wall of the left ventricle. With oligoarticular arthritis in a setting of dilated cardiomyopathy, elevated erythrocyte sedimentation rate, and family history of recurrent unexplained fevers in her mother, a diagnosis of early-onset sarcoidosis was considered. Her eye examination continued to be normal and all biopsies requiring sedation were deferred because of poor cardiac function. Oral methotrexate 10 mg/m 2 and corticosteroids 2 mg/kg were initiated in addition to decongestive treatment consisting of digitalis, diuretics, and captopril. She showed a gradual but steady improvement in effort tolerance, although her ejection fraction on electrocardiography did not mirror her clinical improvement. One and a half years later on a routine followup she was found to be hypertensive. Her carotid pulsations were decreased and a renal bruit was detected. Antihypertensive treatment was instituted and a compute

Personal non-commercial use only

ABSTRACT. Objective. To put forward a new concept -Blau arteritis, a form of large-vessel vasculitis phenotypically related to Takayasu disease but genetically and clinically part of an expanded phenotype of Blau syndrome. Methods. We provide a clinical description of a new case and summarize previously published cases of arteritis associated with Blau syndrome. Genetic testing was performed by direct sequencing of exon 4 of the NOD2 gene. Results. The case described and those reviewed from the literature demonstrate the emerging phenotype of Takayasu-like arteritis in patients with Blau syndrome. Although most patients described to date depict an otherwise classic Blau syndrome phenotype, the current case was atypical in that the predominant features were arteritic. A novel substitution, G464W, in a highly conserved position near the nucleotide oligomerization domain of the NOD2 protein is also described. Blau syndrome is a monogenic granulomatous disease characterized in its most typical form by a triad of exuberant polyarthritis, uveitis, and granulomatous dermatitis 1 . It is caused by single amino acid substitutions at or near the NACHT domain of NOD2 2 . Although its systemic expression is well recognized after the descriptions of the expanded phenotype of Blau syndrome 3,4 , large-vessel vasculitis remains one of its serious and yet underrecognized manifestations if not actively sought by the treating physician. We describe an 8-year-old girl with symptomatic Takayasu-like arteritis and cardiomyopathy against the background of Blau syndrome with a G464W substitution in NOD2. We reported a similar case in 1989 5 , while others have observed arteritis among children with both sporadic and familial Blau phenotype before the mutation was known MATERIALS AND METHODS A girl, now 11 years old, from rural India, presented to us for the first time at 18 months of age, with bilateral knee effusions of a few months' duration in the absence of rash, uveitis, or systemic features. From the age of 1 month she had had recurrent and unexplained episodes of fever. Her antinuclear antibody result was negative. With a working diagnosis of oligoarticular juvenile arthritis she was administered intraarticular steroids, to which she responded well. She was lost to followup for almost 6 years thereafter. At the age of 8 years, she presented with gradually progressive dyspnea and palpitations of 3 months' duration. She had not thrived, and at this stage she weighed 17.2 kg and her height was 113 cm. There were no systemic features but joint examination showed "boggy synovitis" of the right elbow and knee. Cardiovascular examination showed an irregular pulse with a pulsatile precordium and evidence of congestive heart failure. A rhythm strip on electrocardiography showed ventricular extra beats. The echocardiogram revealed dilated ventricles, generalized hypokinesia with an ejection fraction of 20%, mild tricuspid and aortic regurgitation, and abnormal echogenicity within the wall of the left ventricle. With oligoarticular arthritis in a setting of dilated cardiomyopathy, elevated erythrocyte sedimentation rate, and family history of recurrent unexplained fevers in her mother, a diagnosis of early-onset sarcoidosis was considered. Her eye examination continued to be normal and all biopsies requiring sedation were deferred because of poor cardiac function. Oral methotrexate 10 mg/m 2 and corticosteroids 2 mg/kg were initiated in addition to decongestive treatment consisting of digitalis, diuretics, and captopril. She showed a gradual but steady improvement in effort tolerance, although her ejection fraction on electrocardiography did not mirror her clinical improvement. One and a half years later on a routine followup she was found to be hypertensive. Her carotid pulsations were decreased and a renal bruit was detected. Antihypertensive treatment was instituted and a compute

Summary for Policymakers

The Working Group III (WGIII) contribution to the IPCC’s Sixth Assessment Report (AR6) assesses literature on the scientific, technological, environmental, economic and social aspects of mitigation of climate change.The report reflects new findings in the relevant literature and builds on previous IPCC reports, including the WGIII contribution to the IPCC’s Fifth Assessment Report (AR5), the WGI and WGII contributions to AR6 and the three Special Reports in the Sixth Assessment cycle, as well as other UN assessments

Optimum Allocation of Inventory to a Chain of Interconnected Warehouses

Optimum allocation of inventory level for a system of n warehouses which are interconnected with each other has been studied. The analysis has been conducted for the deterministic demands only. The case of instantaneous delivery as well as lead time delivery has been treated