Intrinsic non-uniqueness of the acoustic full waveform inverse problem

SUMMARY In the context of seismic imaging, full waveform inversion (FWI) is increasingly popular. Because of its lower numerical cost, the acoustic approximation is often used, especially at the exploration geophysics scale, both for tests and for real data. Moreover, some research domains such as helioseismology face true acoustic media for which FWI can be useful. In this work, an argument that combines particle relabelling and homogenization is used to show that the general acoustic inverse problem based on band-limited data is intrinsically non-unique. It follows that the results of such inversions should be interpreted with caution. To illustrate these ideas, we consider 2-D numerical FWI examples based on a Gauss–Newton iterative inversion scheme and demonstrate effects of this non-uniqueness in the local optimization context.</jats:p

Regulation and Function of FTO mRNA Expression in Human Skeletal Muscle and Subcutaneous Adipose Tissue

OBJECTIVE-Common variants in FTO (the fat mass- and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN AND METHODS-The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years) nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n = 226) and skeletal muscle biopsies (n = 158). RESULTS-Heritability of FTO expression in both tissues was low, and FTO expression was not influenced by FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA expression. FTO mRNA expression in adipose tissue was associated with an atherogenic lipid profile. In skeletal muscle, FTO mRNA expression was negatively associated to fat and positively to glucose oxidation rates as well as positively correlated with expression of genes involved in oxidative phosphorylation including PGC1 alpha. CONCLUSIONS-The heritability of FTO expression in adipose tissue and skeletal muscle is low and not influenced by obesity-associated FTO genotype. The age-dependent decline in FTO expression is associated with peripheral defects of glucose and fat metabolism. Diabetes 58:2402-2408, 200

Human Body Composition and Immunity: Visceral Adipose Tissue Produces IL-15 and Muscle Strength Inversely Correlates with NK Cell Function in Elderly Humans

Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) are sources of IL-15 and IL-15 Rα, and (2) whether any of these tissues correlate with NK cell activity in elderly humans. We first investigated IL-15 and IL-15Rα RNA expression in paired muscle and SAT biopsies from healthy human subjects. Both tissues expressed these transcripts, but IL-15Rα RNA levels were higher in SAT than in skeletal muscle. We also investigated tissue obtained from surgeries and found that SAT and VAT expressed equivalent amounts of IL-15 and IL-15Rα RNA, respectively. Furthermore, stromal vascular fraction cells expressed more IL-15 RNA than did adipocytes. To test if these findings related to circulating IL-15 protein and NK cell function, we tested 50 healthy adults aged \u3e 70 years old. Plasma IL-15 levels significantly correlated with abdominal VAT mass in the entire cohort and in non-obese subjects. However, plasma IL-15 levels did not correlate with skeletal muscle cross-sectional area and correlated inversely with muscle strength. Plasma IL-15 did correlate with NK cell cytotoxic granule exocytosis and with CCL4 (MIP-1β) production in response to NKp46-crosslinking. Additionally, NK cell responses to K562 leukemia cells correlated inversely with muscle strength. With aging, immune function declines while infections, cancers, and deaths increase. We propose that VAT-derived IL-15 and IL-15Rα is a compensatory NK cell support mechanism in elderly humans

Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging

BACKGROUND: Lipodystrophies are characterized by redistributed subcutaneous fat stores. We previously quantified subcutaneous fat by magnetic resonance imaging (MRI) in the legs of two patients with familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3, respectively). We now extend the MRI analysis across the whole body of patients with different forms of lipodystrophy. METHODS: We studied five subcutaneous fat stores (supraclavicular, abdominal, gluteal, thigh and calf) and the abdominal visceral fat stores in 10, 2, 1, 1 and 2 female subjects with, respectively, FPLD2, FPLD3, HIV-related partial lipodystrophy (HIVPL), acquired partial lipodystrophy (APL), congenital generalized lipodystrophy (CGL) and in six normal control subjects. RESULTS: Compared with normal controls, FPLD2 subjects had significantly increased supraclavicular fat, with decreased abdominal, gluteal, thigh and calf subcutaneous fat. FPLD3 subjects had increased supraclavicular and abdominal subcutaneous fat, with less severe reductions in gluteal, thigh and calf fat compared to FPLD2 subjects. The repartitioning of fat in the HIVPL subject closely resembled that of FPLD3 subjects. APL and CGL subjects had reduced upper body, gluteal and thigh subcutaneous fat; the APL subject had increased, while CGL subjects had decreased subcutaneous calf fat. Visceral fat was markedly increased in FPLD2 and APL subjects. CONCLUSION: Semi-automated MRI-based adipose tissue quantification indicates differences between various lipodystrophy types in these studied clinical cases and is a potentially useful tool for extended quantitative phenomic analysis of genetic metabolic disorders. Further studies with a larger sample size are essential for confirming these preliminary findings

Identification and support of autistic individuals within the UK Criminal Justice System: a practical approach based upon professional consensus with input from lived experience.

Background: Autism Spectrum Disorder (hereafter referred to as autism) is characterised by difficulties with (i) social communication, social interaction, and (ii) restricted and repetitive interests and behaviours. Estimates of autism prevalence within the criminal justice system (CJS) vary considerably, but there is evidence to suggest that the condition can be missed or misidentified within this population. Autism has implications for an individual’s journey through the CJS, from police questioning and engagement in court proceedings through to risk assessment, formulation, therapeutic approaches, engagement with support services, and long-term social and legal outcomes. Methods: This consensus based on professional opinion with input from lived experience aims to provide general principles for consideration by United Kingdom (UK) CJS personnel when working with autistic individuals, focusing on autistic offenders and those suspected of offences. Principles may be transferable to countries beyond the UK. Multidisciplinary professionals and two service users were approached for their input to address the effective identification and support strategies for autistic individuals within the CJS. Results: The authors provide a consensus statement including recommendations on the general principles of effective identification, and support strategies for autistic individuals across different levels of the CJS. Conclusion: Greater attention needs to be given to this population as they navigate the CJS

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n= 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n= 39); IIIB with abdominal multiorgan involvement (n= 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n= 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12–92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2–92.1%) and 83.7% (95% CI 76.3–89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy. © 2000 Cancer Research Campaig

Computer tomographic investigation of subcutaneous adipose tissue as an indicator of body composition

<p>Abstract</p> <p>Background</p> <p>Modern computer tomography (CT) equipment can be used to acquire whole-body data from large animals such as pigs in minutes or less. In some circumstances, computer assisted analysis of the resulting image data can identify and measure anatomical features. The thickness of subcutaneous adipose tissue at a specific site measured by ultrasound, is used in the pig industry to assess adiposity and inform management decisions that have an impact on reproduction, food conversion performance and sow longevity. The measurement site, called "P2", is used throughout the industry. We propose that CT can be used to measure subcutaneous adipose tissue thickness and identify novel measurement sites that can be used as predictors of general adiposity.</p> <p>Methods</p> <p>Growing pigs (<it>N </it>= 12), were each CT scanned on three occasions. From these data the total volume of adipose tissue was determined and expressed as a proportion of total volume (fat-index). A computer algorithm was used to determined 10,201 subcutaneous adipose thickness measurements in each pig for each scan. From these data, sites were selected where correlation with fat-index was optimal.</p> <p>Results</p> <p>Image analysis correctly identified the limits of the relevant tissues and automated measurements were successfully generated. Two sites on the animal were identified where there was optimal correlation with fat-index. The first of these was located 4 intercostal spaces cranial to the caudal extremity of the last rib, the other, a further 5 intercostal spaces cranially.</p> <p>Conclusion</p> <p>The approach to image analysis reported permits the creation of various maps showing adipose thickness or correlation of thickness with other variables by location on the surface of the pig. The method identified novel adipose thickness measurement positions that are superior (as predictors of adiposity) to the site which is in current use. A similar approach could be used in other situations to quantify potential links between subcutaneous adiposity and disease or production traits.</p

FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life: A Meta-Analysis of 41,504 Subjects From the Scandinavian HUNT, MDC, and MPP Studies

OBJECTIVE—FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span. RESEARCH DESIGN AND METHODS—Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians.RESULTS—The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 3 1028) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 3 1028). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m2 per risk allele; P = 2.0 3 10226), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (ΔBMI = 0.0[20.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS—We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter