Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

PubMed

Akinci, Baris; Unlu, Sadiye Mehtat; Celik, Ali; Simsir, Ilgin Yildirim; Sen, Sait; Nur, Banu; Keskin, Fatma Ela; Ozgen Saydam, Basak; Kutbay Ozdemir, Nilufer; Sarer Yurekli, Banu; Ergur, Bekir Ugur; Sonmez, Melda; Atik, Tahir; Arslan, Atakan; Demir, Tevfik; Altay, Canan; Tunc, Ulku Aybuke; Arkan, Tugba; Gen, Ramazan; Eren, Erdal; Akinci, Gulcin; Yilmaz, Aslihan Arasli; Bilen, Habib; Ozen, Samim; Celtik, Aygul; Savas Erdeve, Senay; Cetinkaya, Semra; Onay, Huseyin; Sarioglu, Sulen; Oral, Elif Arioglu

2018-07-01

Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease. © 2018 John Wiley & Sons Ltd.

"We're stuck with what we've got": The impact of lipodystrophy on body image.

PubMed

Adams, Claire; Stears, Anna; Savage, David; Deaton, Christi

2018-05-01

To evaluate the impact of lipodystrophy on body image and how this affects patients' daily lives. Lipodystrophy refers to a group of rare conditions characterised by generalised or partial lack of body fat and is associated with severe metabolic problems, for example, severe insulin resistance, diabetes and pancreatitis. In addition to its metabolic effect, lack of adipose tissue may have a major impact on appearance and cause distressing physical changes. While global research has focused on diagnosis and management, there is no published work investigating the psychological effects of lipodystrophy on body image. Following ethical approval, participants with lipodystrophy were purposively sampled from the National Severe Insulin Resistance Service in Cambridge, UK, and invited to take part in a semi-structured interview. Eleven (10 female, one male) interviews were conducted and digitally recorded. Data were analysed using an inductive thematic approach. Four main themes were identified in the data set; "Always feeling appearance was different," "a better understanding of lipodystrophy is needed," "feeling accepted" and "there's more to lipodystrophy than managing symptoms." Participants spoke of distressing cosmetic effects related to lack of fat tissue and other changes related to lipodystrophy, contributing to negative body image. For some, negative body image led to feelings of worthlessness impacting daily life and adherence to treatment. Psychological support was lacking but desired by participants. Lipodystrophy contributes to negative body image affecting patients' daily lives. Patients wanted psychological support alongside medical management. Further research is needed to determine how best to deliver psychological support and to evaluate its impact on well-being and metabolic management. The effects of rare diseases such as lipodystrophy on appearance can be distressing for patients. Support beyond medical management is needed to improve patients' daily lives and help them to live well with appearance-altering conditions. © 2018 John Wiley & Sons Ltd.

Progranulin is increased in human and murine lipodystrophy.

PubMed

Miehle, Konstanze; Ebert, Thomas; Kralisch, Susan; Hoffmann, Annett; Kratzsch, Jürgen; Schlögl, Haiko; Stumvoll, Michael; Fasshauer, Mathias

2016-10-01

Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far. Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD. Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation. Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation.

PubMed

Renvoisé, Benoît; Malone, Brianna; Falgairolle, Melanie; Munasinghe, Jeeva; Stadler, Julia; Sibilla, Caroline; Park, Seong H; Blackstone, Craig

2016-12-01

Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis. Furthermore, Reep1-/- embryonic fibroblasts and neurons in the cerebral cortex both show lipid droplet abnormalities. The apparent partial lipodystrophy in Reep1 null mice, although less severe, is reminiscent of the lipoatrophy phenotype observed in the most common form of autosomal recessive lipodystrophy, Berardinelli-Seip congenital lipodystrophy. Berardinelli-Seip lipodystrophy is caused by autosomal recessive mutations in the BSCL2 gene that encodes an ER protein, seipin, that is also mutated in the autosomal dominant HSP SPG17 (Silver syndrome). Furthermore, REEP1 co-immunoprecipitates with seipin in cells. This strengthens the link between alterations in ER morphogenesis and lipid abnormalities, with important pathogenic implications for the most common forms of HSP. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

Risk factors in human immunodeficiency virus/acquired immunodeficiency syndrome patients undergoing antiretroviral therapy in the state of Pernambuco, Brazil: a case-control study.

PubMed

Gelenske, Thais; e Farias, Francisco Alfredo Bandeira; de Alencar Ximenes, Ricardo Arraes; de Melo, Heloísa Ramos Lacerda; de Albuquerque, Maria de Fátima Pessoa Militão; de Carvalho, Erico Higino; de Medeiros Barros, Zoraya; Diniz, George Tadeu Nunes; Filho, Demócrito de Barros Miranda

2010-06-01

Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis. A case-control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil. Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs. In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.

[The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (AIDS) patients].

PubMed

Spinola-Castro, Angela Maria; Siviero-Miachon, Adriana A; da Silva, Marcos Tadeu Nolasco; Guerra-Junior, Gil

2008-07-01

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.

Leptin as a Modulator of Neuroendocrine Function in Humans

PubMed Central

Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary

2012-01-01

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy

PubMed Central

Mori, Marcelo A.; Thomou, Thomas; Boucher, Jeremie; Lee, Kevin Y.; Lallukka, Susanna; Kim, Jason K.; Torriani, Martin; Yki-Järvinen, Hannele; Grinspoon, Steven K.; Cypess, Aaron M.; Kahn, C. Ronald

2014-01-01

miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and “whitening” of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte–like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy. PMID:24983316

A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice.

PubMed

Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I

2017-07-01

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.

One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes.

PubMed

Vatier, C; Fetita, S; Boudou, P; Tchankou, C; Deville, L; Riveline, Jp; Young, J; Mathivon, L; Travert, F; Morin, D; Cahen, J; Lascols, O; Andreelli, F; Reznik, Y; Mongeois, E; Madelaine, I; Vantyghem, Mc; Gautier, Jf; Vigouroux, C

2016-07-01

Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [± standard error of the mean (s.e.m.)] age of 39.2 (±4) years, presented with familial partial lipodystrophy (n = 11, 10 women) or congenital generalized lipodystrophy (n = 5, four women). Their mean (± s.e.m.) BMI (23.9 ± 0.7 kg/m(2) ), glycated haemoglobin levels (8.5 ± 0.4%) and serum triglycerides levels (4.6 ± 0.9 mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic-hyperinsulinaemic clamps, n = 4 and n = 12, respectively), insulin secretion during graded glucose infusion (n = 12), and acute insulin response to i.v. glucose adjusted to insulin sensitivity (disposition index, n = 12), significantly increased after 1 year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies. © 2015 John Wiley & Sons Ltd.

Surgical management of HIV-associated lipodystrophy: role of ultrasonic-assisted liposuction and suction-assisted lipectomy in the treatment of lipohypertrophy.

PubMed

Hultman, C Scott; McPhail, Lindsee E; Donaldson, Jeffrey H; Wohl, David A

2007-03-01

HIV-associated lipodystrophy is a frequent consequence of highly active antiretroviral therapy and has been associated with several metabolic disorders (increased triglycerides, hypercholesterolemia, insulin resistance) as well as altered fat distribution, including lipohypertrophy (neck, trunk, breasts) and lipoatrophy (nasolabial fold, cheek, extremities). Medical treatment of fat redistribution is usually ineffective. We evaluated the efficacy and safety of the surgical management of HIV lipodystrophy. We performed a retrospective review of 12 consecutive patients (3 female, 9 male; mean age, 44.4 years; mean CD4+ cell count, 554/mm3; mean body mass index, 28.9 kg/m2; mean triglycerides, 421 mg/dL; no active opportunistic infections; mean duration of HIV infection, 11.4 years) who underwent surgical management of HIV lipodystrophy at a university hospital from 2001 to 2006. Surgical intervention included a combination of ultrasonic-assisted liposuction (UAL) and suction-assisted lipectomy (SAL) of the anterior neck (7 patients), posterior neck (10 patients), and trunk (2 patients); direct excision of mastoid fat pads (1 patient); direct excision of thigh lipomata (1 patient); facelift/necklift (1 patient); browlift (1 patient); fat injections (1 patient); and blepharoplasty (2 patients). Mean lipoaspirate volume was 701 mL (range, 270-1400 mL). Complications and sequelae included seroma (1 patient), ecchymosis (1 patient), need for revision (2 patients), and recurrence (3 patients) but did not include nerve injury, fat necrosis, skin loss, or infection. Although all patients reported improvement in form and function, UAL/SAL of the anterior neck had limited efficacy in 3 of 7 patients. UAL/SAL of the cervicodorsal fat pad was initially successful in 10 of 10 patients, but 3 patients developed partial late (>1 year) recurrence, all associated with weight gain. Mean follow up was 30 months (range, 1-66 months). Despite the potential for recurrence, surgical management of HIV-associated lipodystrophy is efficacious with minimal morbidity. UAL/SAL is particularly beneficial in reducing the cervicodorsal fat pad, whereas facelift and necklift may be necessary to adequately address anterior neck lipohypertrophy.

Human immunodeficiency virus-associated lipodystrophy: an objective definition based on dual-energy x-ray absorptiometry-derived regional fat ratios in a South Asian population.

PubMed

Asha, Hesarghatta Shyamasunder; Seshadri, Mandalam Subramaniam; Paul, Thomas Vizhalil; Abraham, Ooriapadickal Cherian; Rupali, Priscilla; Thomas, Nihal

2012-01-01

To develop an objective definition of human immunodeficiency virus (HIV)-associated lipodystrophy by using regional fat mass ratios and to assess the utility of anthropometric and skinfold measurements in the initial screening for lipodystrophy. Male patients between 25 and 50 years old with proven HIV infection (highly active antiretroviral therapy [HAART]-naïve subjects and those receiving successful HAART) were studied and compared with body mass index (BMI)-matched HIV-negative control subjects. Anthropometric variables, body composition, dual-energy x-ray absorptiometry findings, and metabolic variables were compared among the 3 study groups and between those patients with and those without lipodystrophy. Trunk fat/lower limb fat mass ratio >2.28 identified 54.3% of patients with HIV receiving HAART as having lipodystrophy and had the highest odds ratio for predicting metabolic syndrome. The "clinical diagnosis of lipodystrophy" and the "clinical scoring system" had too many false-positive and false-negative results. Triceps skinfold thickness (SFT)/BMI ratio ≤0.49 and abdominal SFT/triceps SFT ratio >1.385 have good sensitivity but poor specificity in identifying lipodystrophy. In comparison with HAART-naïve patients with HIV, those receiving HAART had significantly higher insulin resistance, and a significantly greater proportion had impaired glucose tolerance and dyslipidemia. Among patients receiving HAART, those with lipodystrophy had a greater degree of insulin resistance, higher triglyceride levels, and lower levels of high-density lipoprotein cholesterol. The trunk fat/lower limb fat mass ratio in BMI-matched normal subjects can be used to derive cutoff values to define lipodystrophy objectively in HIV-infected patients. Defining lipodystrophy in this way is better than other methods of identifying those patients with increased cardiovascular risk. Triceps SFT/BMI and abdominal SFT/triceps SFT ratios may be useful as screening tools in resource-poor settings.

Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.

PubMed

Joseph, Jalaja; Shamburek, Robert D; Cochran, Elaine K; Gorden, Phillip; Brown, Rebecca J

2014-09-01

There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%). Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome. This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy. Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy. Serum triglycerides and HDL-C were measured. At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C. The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.

Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives

PubMed Central

Vigouroux, Corinne; Guénantin, Anne-Claire; Vatier, Camille; Le Dour, Caroline; Afonso, Pauline; Bidault, Guillaume; Béréziat, Véronique; Lascols, Olivier; Capeau, Jacqueline; Briand, Nolwenn; Jéru, Isabelle

2018-01-01

Abstract Mutations in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and premature ageing syndromes. LMNA mutations have been shown to alter nuclear structure and stiffness, binding to partners at the nuclear envelope or within the nucleoplasm, gene expression and/or prelamin A maturation. LMNA-associated lipodystrophic features, combining generalized or partial fat atrophy and metabolic alterations associated with insulin resistance, could result from altered adipocyte differentiation or from altered fat structure. Recent studies shed some light on how pathogenic A-type lamin variants could trigger lipodystrophy, metabolic complications, and precocious cardiovascular events. Alterations in adipose tissue extracellular matrix and TGF-beta signaling could initiate metabolic inflexibility. Premature senescence of vascular cells could contribute to cardiovascular complications. In affected families, metabolic alterations occur at an earlier age across generations, which could result from epigenetic deregulation induced by LMNA mutations. Novel cellular models recapitulating adipogenic developmental pathways provide scalable tools for disease modeling and therapeutic screening. PMID:29578370

Lipid Regulation in Lipodystrophy Versus the Obesity-Associated Metabolic Syndrome: The Dissociation of HDL-C and Triglycerides

PubMed Central

Joseph, Jalaja; Shamburek, Robert D.; Cochran, Elaine K.; Gorden, Phillip

2014-01-01

Context: There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%). Objective: Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome. Design, Setting, and Patients: This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy. Intervention: Metreleptin (0.06–0.24 mg/kg/d) was administered for 24 months in lipodystrophy. Main Outcome Measures: Serum triglycerides and HDL-C were measured. Results: At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = −0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C. Conclusions: The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition. PMID:24926953

Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy.

PubMed

Kolter, Donald P

2003-12-01

HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.

HIV lipodystrophy etiology and pathogenesis. Body composition and metabolic alterations: etiology and pathogenesis.

PubMed

Kotler, Donald P

2003-04-01

The results of epidemiologic investigations have clearly indicated that the development of lipodystrophy is multifactorial. Factors related to HIV infection, hormonal influences, mitochondrial dysfunction, cytokine activation related to immune reconstitution, and individual genetic predisposition all have been hypothesized as etiologic. Recent studies suggest that immune dysregulation rather than HIV infection per se may be the predominant factor in the development of lipodystrophy.

The successful use of lipectomy in the management of airway obstruction in a woman with HIV-associated lipodystrophy

PubMed Central

Tsui, Edison; Bogdasarian, Ronald; Blomain, Eric

2015-01-01

Lipodystrophy is a common complication of highly active antiretroviral therapy and is associated with significant comorbidities. Altered fat distribution, particularly lipohypertrophy of the dorsal cervical fat pad is associated with reduced quality of life as well as medical complications. We report the rare case of a patient with airway obstruction secondary to HIV-associated lipodystrophy. Ultrasound-assisted liposuction was successfully performed to relieve her airway obstruction and to facilitate a tracheostomy. To the best of our knowledge, this is the first documented case of its kind. We also provide a brief review of the literature on the current management options for HIV-associated lipodystrophy. PMID:25694636

Membranous lipodystrophy: case report and review of the literature.

PubMed

Akpinar, Fatma; Demir, Ektan; Apa, Duygu Dusmez

2015-01-01

Membranous lipodystrophy is a distinct type of membranocystic fat necrosis. It is associated with many local and systemic diseases, including vascular disorders. The histopathological changes which characterize this phenomenon are variably sized cysts in the fat lobules of the subcutaneous tissue, which are surrounded by eosinophilic membranes projecting into the cystic space. We report a case of secondary membranous lipodystrophy associated with both hypertension and venous insufficiency.

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

PubMed

Hadigan, C; Meigs, J B; Corcoran, C; Rietschel, P; Piecuch, S; Basgoz, N; Davis, B; Sax, P; Stanley, T; Wilson, P W; D'Agostino, R B; Grinspoon, S

2001-01-01

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Liposuction for lower limb lipodystrophy in congenital analbuminaemia: a case report.

PubMed

Kandamany, Nanda; Munnoch, Alex

2014-02-01

Congenital analbuminaemia is a very rare autosomal dominant disorder in which patients have no serum albumin and markedly low serum total protein concentration. Clinically patients present with mild oedema, hypotension, fatigue and lipodystrophy often with abnormal body habitus. With only around 50 reported cases in the literature worldwide, management of the resulting lipodystrophy remains unclear. A 42-year-old male who was diagnosed with congenital analbuminaemia presented with bilateral lower limb lipodystrophy disproportionately affecting his thighs. This was associated with concerns over appearance, difficulties with mobility and finding clothing. He successfully underwent bilateral lower leg liposuction and has had no recurrence of his symptoms after 12 months. We have demonstrated that liposuction along with controlled compression therapy is a safe and effective treatment for managing lipodystrophy secondary to congenital analbuminaemia. Although rare, clinicians need to be aware that liposuction is a successful treatment modality, which should be made available to this select group of patients. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

[Lipodystrophy and metabolic disturbances as complications of antiretroviral therapy].

PubMed

Bociaga-Jasik, Monika; Kieć-Wilk, Beata; Kalinowska-Nowak, Anna; Mach, Tomasz; Garlicki, Aleksander

2010-01-01

Effective treatment of HIV infection with antiretroviral drugs significantly improve prognosis. Reduction of mortality and life prolongations in patients receiving such therapy have been also connected with the risk of side effects development. Among these complications metabolic disturbances such as lipodystrophy, dyslipidaemia, and insulin resistance which are present according some authors in up to 50% of patients receiving HAART play an important role. In spite of different investigations molecular basis of lipodystrophy development during HAART have not be fully understood, and the latest research revealed a lot of new aspects connected w adipocyte tissue pathophysiology, which were not taken up to know into consideration. In the presented publication the most important information about pathogenesis of lipodystrophy development in HIV infected patients treated with ARV drugs have been presented.

HIV/AIDS and lipodystrophy: implications for clinical management in resource-limited settings.

PubMed

Finkelstein, Julia L; Gala, Pooja; Rochford, Rosemary; Glesby, Marshall J; Mehta, Saurabh

2015-01-01

Lipodystrophy is a term used to describe a metabolic complication of fat loss, fat gain, or a combination of fat loss and gain, which is associated with some antiretroviral (ARV) therapies given to HIV-infected individuals. There is limited research on lipodystrophy in low- and middle-income countries, despite accounting for more than 95% of the burden of HIV/AIDS. The objective of this review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in resource-limited settings. We conducted a structured literature search using MEDLINE electronic databases. Relevant MeSH terms were used to identify published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed syndrome in low-, low-middle- and upper-middle-income countries through 31 March 2014. The search resulted in 5296 articles; after 1599 studies were excluded (958 reviews, 641 non-human), 3697 studies were extracted for further review. After excluding studies conducted in high-income settings (n=2808), and studies that did not meet inclusion criteria (n = 799), 90 studies were included in this review. Of the 90 studies included in this review, only six were from low-income countries and eight were from lower middle-income economies. These studies focused on lipodystrophy prevalence, risk factors and side effects of antiretroviral therapy (ART). In most studies, lipodystrophy developed after the first six months of therapy, particularly with the use of stavudine. Lipodystrophy is associated with increased risk of cardiometabolic complications. This is disconcerting and anticipated to increase, given the rapid scale-up of ART worldwide, the increasing number and lifespan of HIV-infected patients on long-term therapy, and the emergence of obesity and non-communicable diseases in settings with extensive HIV burden. Lipodystrophy is common in resource-limited settings, and has considerable implications for risk of metabolic diseases, quality of life and adherence. Comprehensive evidence-based interventions are urgently needed to reduce the burden of HIV and lipodystrophy, and inform clinical management in resource-limited settings.

Mapping disease-related missense mutations in the immunoglobulin-like fold domain of lamin A/C reveals novel genotype-phenotype associations for laminopathies.

PubMed

Scharner, Juergen; Lu, Hui-Chun; Fraternali, Franca; Ellis, Juliet A; Zammit, Peter S

2014-06-01

Mutations in A-type nuclear lamins cause laminopathies. However, genotype-phenotype correlations using the 340 missense mutations within the LMNA gene are unclear: partially due to the limited availability of three-dimensional structure. The immunoglobulin (Ig)-like fold domain has been solved, and using bioinformatics tools (including Polyphen-2, Fold X, Parameter OPtimized Surfaces, and PocketPicker) we characterized 56 missense mutations for position, surface exposure, change in charge and effect on Ig-like fold stability. We find that 21 of the 27 mutations associated with a skeletal muscle phenotype are distributed throughout the Ig-like fold, are nonsurface exposed and predicted to disrupt overall stability of the Ig-like fold domain. Intriguingly, the remaining 6 mutations clustered, had higher surface exposure, and did not affect stability. The majority of 9 lipodystrophy or 10 premature aging syndrome mutations also did not disrupt Ig-like fold domain stability and were surface exposed and clustered in distinct regions that overlap predicted binding pockets. Although buried, the 10 cardiac mutations had no other consistent properties. Finally, most lipodystrophy and premature aging mutations resulted in a -1 net charge change, whereas skeletal muscle mutations caused no consistent net charge changes. Since premature aging, lipodystrophy and the subset of 6 skeletal muscle mutations cluster tightly in distinct, charged regions, they likely affect lamin A/C -protein/DNA/RNA interactions: providing a consistent genotype-phenotype relationship for mutations in this domain. Thus, this subgroup of skeletal muscle laminopathies that we term the 'Skeletal muscle cluster', may have a distinct pathological mechanism. These novel associations refine the ability to predict clinical features caused by certain LMNA missense mutations. © 2013 Wiley Periodicals, Inc.

Side Effects of HIV Medicines: HIV and Lipodystrophy

MedlinePlus

... may help. Other ways to manage lipodystrophy include liposuction (surgical removal of fat) and injections of fat ... unless your health care provider tells you to. Liposuction (surgical removal of fat) is sometimes used to ...

CASE REPORT OF SEVERE PROLIFERATIVE RETINOPATHY IN A PATIENT WITH CONGENITAL LIPODYSTROPHY.

PubMed

Rosin, Boris; Jaouni, Tareq

2017-08-21

A case report of a patient with severe proliferative retinopathy due to congenital lipodystrophy. We reviewed the medical history, imaging, and surgical procedures of a 25-year-old woman with a history of congenital lipodystrophy, presenting with bilateral combined tractional and exudative retinal detachment, poorly controlled diabetes mellitus, and extreme dislipidemia. The patient underwent retinal detachment repair surgery both eyes. On the last follow-up, both retinae were flat, and visual acuity had improved in the right eye to J3 for near and finger counting 3 m for distance. Surgery combining pars plana vitrectomy and scleral bucking successfully flattened both retinae and significantly improved visual acuity in one eye in this case of bilateral retinal detachment with combined tractional and exudative components in a patient with congenital lipodystrophy. Surgical control of retinal complications is thus possible, provided there is adequate control of the underlying risk factors.

A new method for body fat evaluation, body adiposity index, is useful in women with familial partial lipodystrophy.

PubMed

Godoy-Matos, Amélio F; Moreira, Rodrigo O; Valerio, Cynthia M; Mory, Patricia B; Moises, Regina S

2012-02-01

BMI is a widely used method to evaluate adiposity. However, it has several limitations, particularly an inability to differentiate lean from fat mass. A new method, body adiposity index (BAI), has been recently proposed as a new measurement capable to determine fat excess better than BMI. The aim of this study was to investigate BAI as a mean to evaluate adiposity in a group of women with familial partial lipodystrophy (FPLD) and compare it with BMI. Thirteen women with FLPD Dunnigan type (FPLD2) and 13 healthy volunteers matched by age and BMI were studied. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Plasma leptin was also measured. BAI was significantly lower in FPLD2 in comparison to control group (24.6 ± 1.5 vs. 30.4 ± 4.3; P < 0.001) and presented a more significant correlation with total fat (%) (r = 0.71; P < 0.001) and fat Mass (g) (r = 0.80; P < 0.001) than BMI (r = 0.27; P = 0.17 for total fat and r = 0.52; P = 0.006 for fat mass). There was a correlation between leptin and BAI (r = 0.57; P = 0.01), [corrected] but not between leptin and BMI. In conclusion, BAI was able to catch differences in adiposity in a sample of FPLD2 patients. It also correlated better with leptin levels than BMI. Therefore, we provide further evidence that BAI may become a more reliable indicator of fat mass content than the currently available measurements.

Regulation of adiponectin in adipocytes upon exposure to HIV-1

USDA-ARS?s Scientific Manuscript database

Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose...

[Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids improves body composition and lipid profile in a patient with human immunodeficiency virus lipodystrophy].

PubMed

Vázquez, C; Reyes, R; Alcaraz, F; Balsa, J A; Botella-Carretero, J I

2006-01-01

Lipodystrophy is a frequent disorder among patients with human immunodeficiency virus (HIV) infection, characterized by a loss of adipose tissue from the extremities, gluteal region and face, with excess fat in the neck and abdominal region. Metabolic abnormalities such as hyperlipidaemia and diabetes mellitus frequently coexist, posing these patients to an increased cardiovascular risk. Drug therapy may improve some of these metabolic disturbances, but to date there are no treatments for lipodystrophy with proven benefit. A 42-year-old man with HIV lipodystrophy was started on a standard low caloric diet with <30% of total fat and <10% of saturated fat, together with rosiglitazone 8 mg daily. After five months of treatment, given that lipodystrophic features and dyslipidaemia were still present in our patient, we tried to further improve therapeutic results by eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids. Three months later, a dramatic change in body composition was shown with an increase in lean mass and a decrease in fat mass, together with an improvement in lipid profile. Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids may produce therapeutic benefits in HIV lipodystrophy.

HIV-associated lipodystrophy syndrome: A review of clinical aspects

PubMed Central

Baril, Jean-Guy; Junod, Patrice; LeBlanc, Roger; Dion, Harold; Therrien, Rachel; Laplante, François; Falutz, Julian; Côté, Pierre; Hébert, Marie-Nicole; Lalonde, Richard; Lapointe, Normand; Lévesque, Dominic; Pinault, Lyse; Rouleau, Danielle; Tremblay, Cécile; Trottier, Benoît; Trottier, Sylvie; Tsoukas, Chris; Weiss, Karl

2005-01-01

Approximately two years after the introduction of highly active antiretroviral therapy for the treatment of HIV infection, body shape changes and metabolic abnormalities were increasingly observed. Initially, these were ascribed to protease inhibitors, but it is now clear that nucleoside reverse transcriptase inhibitors also contribute to lipodystrophy syndrome. The syndrome groups together clinical conditions describing changes in body fat distribution that include lipoatrophy, lipoaccumulation or both. However, there does not appear to be a direct link between lipoatrophy and lipoaccumulation that would support a single mechanism for the redistribution of body fat. Currently, there is no clear definition of lipodystrophy, which explains the difficulty in determining its prevalence and etiology. There are no current guidelines for the treatment of fat distribution abnormalities that occur in the absence of other metabolic complications. The present article reviews the current state of knowledge of the definition, symptoms, risk factors, pathogenesis, diagnosis and treatment of the morphological changes associated with lipodystrophy syndrome. PMID:18159551

Berardinelli-Seip congenital lipodystrophy in two siblings

PubMed Central

Rao, T. S. Mohana; Chennamsetty, Kavya

2014-01-01

Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare autosomal recessive disorder characterized by various dermatological and systemic manifestations such as lipoatrophy, hypertriglyceridemia, hepatomegaly, acanthosis nigricans, and acromegaloid features. BSCL type 2 is more common and severe, with onset in the neonatal period or in early infancy. The locus for BSCL2 has been identified on chromosome 11q13. Early recognition and differentiation from other congenital generalized lipodystrophies help in the initiation of appropriate preventive and therapeutic measures such as lifestyle modification and pharmacotherapy that helps postpone the onset of metabolic syndrome. We report BSCL type 2 in two siblings with several cutaneous manifestations like acanthosis nigricans, hypertrichosis, prominent subcutaneous veins, and increased lanugo hair. PMID:25506557

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

PubMed

Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

[Polyalkylimide filler in human immunodeficiency virus-associated facial lipodystrophy: ophthalmic complications].

PubMed

García-Pacheco, S A; Blanco-Rivas, R; Campos-García, S

2014-10-01

A 54 year old male, who consulted for acute inflammatory palpebral edema. The patient has HIV infection (on antiretroviral treatment) and an associated facial lipodystrophy that was filled with polyalkylimide in both frontotemporal regions one year before. MRI revealed subcutaneous abscesses in the filled areas, which led to preseptal cellulitis. Complete remission was achieved with antibiotic therapy and monitoring. Polyalkylimide is a hydrogel that is recently used as facial filler without FDA approval. Although it was believed to be safe and useful for treating HIV lipodystrophy, it is not exempt from adverse effects (infection, abscesses, granulomas) that can compromise the eye area. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

PubMed Central

Indumathi, C. K.; Lewin, S.; Ayyar, Vageesh

2011-01-01

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age. PMID:21847459

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant.

PubMed

Indumathi, C K; Lewin, S; Ayyar, Vageesh

2011-07-01

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

In vivo evidence of impaired peripheral fatty acid trapping in patients with human immunodeficiency virus-associated lipodystrophy.

PubMed

van Wijk, J P H; Cabezas, M Castro; de Koning, E J P; Rabelink, T J; van der Geest, R; Hoepelman, I M

2005-06-01

The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.

The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation.

PubMed

Chen, Weiqin; Yechoor, Vijay K; Chang, Benny Hung-Junn; Li, Ming V; March, Keith L; Chan, Lawrence

2009-10-01

Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of Bscl2 in the regulation of adipocyte differentiation. Bscl2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-gamma agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated Bscl2 expression. On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that Bscl2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-gamma, enabling the latter to exert its full activity during adipogenesis. Loss of Bscl2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

HIV protease inhibitor-related lipodystrophy syndrome.

PubMed

Carr, A

2000-06-01

Human immunodeficiency virus (HIV) protease inhibitor (PI) therapy is frequently associated with a syndrome increasingly referred to as lipodystrophy syndrome, which is characterized by peripheral lipoatrophy, fat accumulation within the abdomen, in the breasts of women, and over the cervical vertebrae ("buffalo hump"), hyperlipidemia, and insulin resistance. In the largest study to date, peripheral lipoatrophy (an estimated 0.35-kg fat loss per month overall from the face, limbs, and upper trunk) was observed in association with all licensed PIs after a median 10 months of PI therapy. Diabetes mellitus type II appears to be a related, but less common, adverse effect. The lipodystrophy syndrome may be a result of the inhibition of 2 proteins involved in lipid metabolism that have significant homology to the catalytic site of HIV protease-namely, cytoplasmic retinoic acid binding protein type 1 and low density lipoprotein-receptor-related protein.

[A complex case of diabetes due to LMNA mutation].

PubMed

Ambonville, C; Bouldouyre, M-A; Laforêt, P; Richard, P; Benveniste, O; Vigouroux, C

2017-10-01

Laminopathies (diseases related to A/C mutations of lamines) are rare genetic diseases with an extensive phenotypic spectrum, including lipodystrophic syndromes-characterized by a selective loss of adipose tissue-of which the partial Dunnigan family type is the most frequent. We report on a 55-year-old woman with diabetes and long-term disabling myalgia. Her cushingoid morphotype, associated with cutaneous lipo-atrophy and muscle hypertrophy in addition to a genetic heritage, led us to the diagnosis of complex partial familial lipodystrophy heterozygous LMNA_c.82C>T, p.Arg28Trp mutation. Familial partial lipodystrophic syndromes may have varied phenotypes, mainly cardio-metabolic, which could mimic a particularly severe type 2 diabetes. The diagnostic work-up of this disease has to include a careful investigation of gait troubles and paroxysmal conduction that could lead to sudden death, as well as a genetic examination. In some cases, recombinant leptin can be proposed. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Hypotension, lipodystrophy, and insulin resistance in generalized PPARγ-deficient mice rescued from embryonic lethality

PubMed Central

Duan, Sheng Zhong; Ivashchenko, Christine Y.; Whitesall, Steven E.; D’Alecy, Louis G.; Duquaine, Damon C.; Brosius, Frank C.; Gonzalez, Frank J.; Vinson, Charles; Pierre, Melissa A.; Milstone, David S.; Mortensen, Richard M.

2007-01-01

We rescued the embryonic lethality of global PPARγ knockout by breeding Mox2-Cre (MORE) mice with floxed PPARγ mice to inactivate PPARγ in the embryo but not in trophoblasts and created a generalized PPARγ knockout mouse model, MORE-PPARγ knockout (MORE-PGKO) mice. PPARγ inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPARγ agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MORE-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to α-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPARγ is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPARγ function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation. PMID:17304352

Leptin applications in 2015: What have we learned about leptin and obesity?

PubMed Central

Farr, Olivia M.; Gavrieli, Anna; Mantzoros, Christos S.

2015-01-01

Purpose of review To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity. Recent findings The discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to effectively treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin resistance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but may be useful in combination with other therapies or for weight loss maintenance. Summary Leptin is not yet able to treat typical obesity, however, it is effective for reversing leptin deficiency-induced obesity and lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, while the development of new techniques and drug combinations which may improve leptin’s efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity. PMID:26313897

Metabolic Abnormalities and Clinical Lipodystrophy in Children With Human Immunodeficiency Virus Infection: A Report From a Tertiary Care Center in India.

PubMed

Kumar, Prasanna; Suri, Deepti; Vignesh, Pandiarajan; Verma Attri, Savita; Kumar Bhalla, Anil; Singh, Surjit

2017-12-01

A cross-sectional study from a tertiary care center in India was undertaken to assess and compare the prevalence of blood glucose and lipid profile aberrations in children who received first-line antiretroviral therapy (ART; n = 63) and in children who were naïve to ART (n = 46). Impaired fasting blood glucose values were found in 7 children in ART-experienced group but none in ART-naïve group (P = 0.02). Low concentrations of high-density lipoprotein cholesterol were more prevalent in the ART-naïve group compared with ART-experienced group (54.3% vs. 22.2%; P = 0.001). Hypertriglyceridemia was noted in a significant proportion of both ART-naïve (43.5%) and ART-experienced children (39.7%). Incidence of clinical lipodystrophy was 47.7%, and there was no significant association noted between lipid profile abnormalities and lipodystrophy.

[Congenital generalized lipodystrophy in a patient with Dandy Walker anomaly].

PubMed

Luna, Cecilia Inés; Fernández Cordero, Marisa; Escruela, Romina; Sierra, Valeria; Córdoba, Antonela; Goñi, Ignacio María; Berridi, Ricardo

2014-10-01

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance should be given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.

Iatrogenic lipodystrophy in HIV patients - the need for very-low-fat diets.

PubMed

McCarty, M F

2003-01-01

In HIV patients, chronic treatment with protease inhibitors often precipitates a peripheral lipodystrophy associated with insulin resistance syndrome and premature coronary disease. In vitro studies demonstrate that these drugs can compromise the ability of adipocytes to store triglycerides; in vivo, peripheral subcutaneous adipocytes appear to be most affected, such that body fat often redistributes to visceral or truncal adipose stores. Dysfunction of peripheral subcutaneous adipocytes - ordinarily quite efficient for storing fat - can be expected to give rise to an excessive flux of free fatty acids (FFAs) following fatty meals; chronic overexposure of tissues to FFAs is a likely explanation for the insulin resistance syndrome associated with lipodystrophy. These considerations suggest that a very-low-fat diet - less than 15% fat calories - may ameliorate the cardiovascular risk associated with lipodystrophy; such diets are known to have a favorable effect on the insulin sensitivity of healthy subjects. Very-low-fat whole-food vegan diets are particularly recommendable in this context, as they may help to shrink visceral fat depots while markedly reducing LDL cholesterol. Appropriate adjunctive measures may include aerobic exercise training - beneficial both for insulin sensitivity and weight control - as well as administration of statins or policosanol, and of fibrates or fish oil, to decrease LDL and triglycerides, respectively. Despite perceptions to the contrary, very-low-fat diets can meet with good compliance in well-motivated subjects given appropriate instruction.

Substituting Abacavir for Stavudine in Children Who Are Virally Suppressed Without Lipodystrophy: Randomized Clinical Trial in Johannesburg, South Africa.

PubMed

Strehlau, Renate; Shiau, Stephanie; Arpadi, Stephen; Patel, Faeezah; Pinillos, Francoise; Tsai, Wei-Yann; Coovadia, Ashraf; Abrams, Elaine; Kuhn, Louise

2018-01-24

Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen. At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally suppressed human immunodeficiency virus (HIV)-infected children ≥36 months of age without lipodystrophy were randomly assigned to continue taking stavudine as part of their ART regimen (n = 106) or to have abacavir substituted for stavudine (n = 107). The children were followed for 56 weeks after randomization in the context of a larger trial of treatment options for ART-experienced children. The mean age of the children was 4.3 years, and the mean duration of ART before random assignment was 3.5 years. No differences in virological outcomes, CD4 response, growth, or dyslipidemia were noted between the stavudine and abacavir groups. By 56 weeks, children in the abacavir group had less clinically detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg fat relative to total fat (0.243 vs 0.230, respectively; P = .006), and a lower trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P = .003) than the children in the stavudine group. Substituting abacavir for stavudine did not compromise virological response to treatment and was associated with significantly less lipodystrophy. These results support recommendations that favor abacavir in this population. © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Features of Acquired Immunodeficiency Syndrome-related Lymphoma on (18)F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography].

PubMed

Niu, Na; Zhu, Zhao-hui; Ma, Yan-ru; Xing, Hai-qun; Li, Fang

2015-10-01

To analyze the imaging features of (18)F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography(PET)/computed tomography (CT) in acquired immune deficiency syndrome-related lymphoma (ARL) patients correlated with their clinical signs, symptoms, and treatments. Five ARL patients underwent ¹⁸F-FDG PET/CT at Peking Union Medical College Hospital from October 2008 to January 2013. Two patients received two additional follow-up studies 6 months later. Among these 5 patients, ¹⁸FDG-PET/CT helped in diagnosis of two patient and changed therapeutic strategy in other two patients. In two patients underwent ¹⁸F-FDG PET/CT brain scans, low-metabolism lesion was newly found in cerebral cortex. Of 4 patients receiving highly active antiretroviral therapy, PET/CT also demonstrated diffusely elevated ¹⁸F-FDG uptake in subcutaneous adipose tissue in two patients. ¹⁸F-FDG PET/CT is a highly useful tool in the diagnosis and treatment of ARL patients, in particular in the identification of associated encephalopathy and lipodystrophy.

Nursing sickness in the mink--a metabolic mystery or a familiar foe?

PubMed

Rouvinen-Watt, Kirsti

2003-07-01

Nursing sickness, the largest single cause of mortality in adult female mink (Mustela vison), is an example of a metabolic disorder, which develops when the demands for lactation require extensive mobilization of body energy reserves. The condition is characterized by progressive weight loss, emaciation, and dehydration with high concentrations of glucose and insulin in the blood. Morbidity due to nursing sickness can be as high as 15% with mortality around 8%, but the incidence is known to vary from year to year. Stress has been shown to trigger the onset of the disease and old females and females with large litters are most often affected. Increasing demand for gluconeogenesis from amino acids due to heavy milk production may be a predisposing factor. Glucose metabolism is inextricably linked to that of protein and fats. In obesity (or lipodystrophy), the ability of adipose tissue to buffer the daily influx of nutrients is overwhelmed (or absent), interfering with insulin-mediated glucose disposal and leading to insulin resistance. Polyunsaturated fatty acids of the n-3 family play an important role in modulating insulin signalling and glucose uptake by peripheral tissue. The increasing demand on these fatty acids for milk fat synthesis towards late lactation may result in deficiency in the lactating female, thus impairing glucose disposal. It is suggested that the underlying cause of mink nursing sickness is the development of acquired insulin resistance with 3 contributing key elements: obesity (or lipodystrophy), n-3 fatty acid deficiency, and high protein oxidation rate. It is recommended that mink breeder females be kept in moderate body condition during fall and winter to avoid fattening or emaciation. A dietary n-3 fatty acid supplement during the lactation period may be beneficial for improved glycemic control. Lowering of dietary protein reduces (oxidative) stress and improves water balance in the nursing females and may, therefore, prevent the development and help in the management of nursing sickness. It is also surmised that other, thus far unexplained, metabolic disorders seen in male and female mink may be related to acquired insulin resistance.

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection.

PubMed

Okada, Asami; Kohmoto, Tomohiro; Naruto, Takuya; Yokota, Ichiro; Kotani, Yumiko; Shimada, Aki; Miyamoto, Yoko; Takahashi, Rizu; Goji, Aya; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2017-01-01

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case.

4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. San Diego, California, USA 22-25 September 2002.

PubMed

Nolan, David; Christiansen, Frank

2003-01-01

Highlights are presented from this annual workshop, which was devoted to the investigation of adverse effects associated with antiretroviral therapy for HIV infection. Topics covered included the lipodystrophy syndrome, which encompasses body composition changes (subcutaneous fat wasting, visceral fat accumulation) and metabolic abnormalities (insulin resistance and dyslipidaemia). The relevance of HIV protease inhibitor-induced metabolic abnormalities to cardiovascular disease is discussed. Research in the areas of hyperlactataemia, abacavir hypersensitivity, and bone mineral density in the context of HIV infection is also briefly reviewed.

Hepatic Lipodystrophy in Galloway Calves.

PubMed

Wieland, M; Mann, S; Hafner-Marx, A; Ignatius, A; Metzner, M

2017-05-01

Hepatic lipodystrophy in Galloway calves is a fatal liver disease affecting a small proportion of the Galloway breed described in different parts of Europe and North America during the past decades. The clinical findings include a diversity of neurological signs. Clinical pathology findings frequently indicate hepatobiliary disease. Postmortem examination reveals an enlarged, pale yellow, and firm liver. Histologic lesions include hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. To date, the etiopathogenesis remains obscure. Infectious causes, intoxications, and a hereditary origin have been considered. We describe hepatic lipodystrophy in Galloway calves from an extensively farmed cow-calf operation in southern Germany. Main clinical findings in 6 calves were consistent with hepatic encephalopathy. Clinical pathology findings in 5 of 6 tested animals revealed increased concentration of total bilirubin (maximum value [MV], 54 μmol/l; reference range [RR], <8.5 μmol/l), direct bilirubin (MV, 20 μmol/l; RR, <3.4 μmol/l), increased activity of gamma glutamyl transferase (MV, 162 U/l; RR, <36 U/l) and glutamate dehydrogenase (MV, 420 U/l; RR, <16 U/l). In addition, activity of glutathione peroxidase was decreased in all tested ( n = 5) animals (MV, 61 U/g hemoglobin [Hb]; RR, >250 U/g Hb). Postmortem examination in 6 calves revealed a firm, diffusely enlarged yellow liver with a finely nodular surface. Histologic lesions included hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. Our findings add to the existing data on hepatic lipodystrophy in the Galloway breed and outline a protocol to aid in the diagnosis of this disorder.

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection

PubMed Central

Okada, Asami; Kohmoto, Tomohiro; Naruto, Takuya; Yokota, Ichiro; Kotani, Yumiko; Shimada, Aki; Miyamoto, Yoko; Takahashi, Rizu; Goji, Aya; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2017-01-01

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case. PMID:28791128

Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue in Patients With and Without Antiretroviral Therapy–Associated Lipodystrophy

PubMed Central

Sevastianova, Ksenia; Sutinen, Jussi; Greco, Dario; Sievers, Meline; Salmenkivi, Kaisa; Perttilä, Julia; Olkkonen, Vesa M.; Wågsäter, Dick; Lidell, Martin E.; Enerbäck, Sven; Eriksson, Per; Walker, Ulrich A.; Auvinen, Petri; Ristola, Matti; Yki-Järvinen, Hannele

2011-01-01

OBJECTIVE Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1–infected cART-treated patients with (cART+LD+) and without (cART+LD−) lipodystrophy. RESEARCH DESIGN AND METHODS We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n = 21) and cART+LD− (n = 11). RESULTS Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD−. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes. PMID:21602514

New Described Dermatological Disorders

PubMed Central

Cevirgen Cemil, Bengu; Keseroglu, Havva Ozge; Kaya Akis, Havva

2014-01-01

Many advances in dermatology have been made in recent years. In the present review article, newly described disorders from the last six years are presented in detail. We divided these reports into different sections, including syndromes, autoinflammatory diseases, tumors, and unclassified disease. Syndromes included are “circumferential skin creases Kunze type” and “unusual type of pachyonychia congenita or a new syndrome”; autoinflammatory diseases include “chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome,” “pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome,” and “pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome”; tumors include “acquired reactive digital fibroma,” “onychocytic matricoma and onychocytic carcinoma,” “infundibulocystic nail bed squamous cell carcinoma,” and “acral histiocytic nodules”; unclassified disorders include “saurian papulosis,” “symmetrical acrokeratoderma,” “confetti-like macular atrophy,” and “skin spicules,” “erythema papulosa semicircularis recidivans.” PMID:25243162

Laminopathies and the long strange trip from basic cell biology to therapy

PubMed Central

Worman, Howard J.; Fong, Loren G.; Muchir, Antoine; Young, Stephen G.

2009-01-01

The main function of the nuclear lamina, an intermediate filament meshwork lying primarily beneath the inner nuclear membrane, is to provide structural scaffolding for the cell nucleus. However, the lamina also serves other functions, such as having a role in chromatin organization, connecting the nucleus to the cytoplasm, gene transcription, and mitosis. In somatic cells, the main protein constituents of the nuclear lamina are lamins A, C, B1, and B2. Interest in the nuclear lamins increased dramatically in recent years with the realization that mutations in LMNA, the gene encoding lamins A and C, cause a panoply of human diseases (“laminopathies”), including muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes. Here, we review the laminopathies and the long strange trip from basic cell biology to therapeutic approaches for these diseases. PMID:19587457

Successful Treatment of an Unusual Case of FPLD2: The Role of Roux-en-Y Gastric Bypass-Case Report and Literature Review.

PubMed

Grundfest-Broniatowski, Sharon; Yan, JingLiang; Kroh, Matthew; Kilim, Holly; Stephenson, Andrew

2017-04-01

Familial partial lipodystrophy type 2 (FPLD2) is a rare disorder associated with LMNA gene mutations. It is usually marked by loss of subcutaneous fat on the limbs and trunk and severe insulin resistance. Scattered reports have indicated that Roux-en-Y bypass helps to control the diabetes mellitus in these patients. We present here a very unusual patient with FPLD2 who had life-threatening retroperitoneal and renal fat accumulation accompanied by bilateral renal cancers. Following cryotherapy of one renal cancer and a contralateral nephrectomy with debulking of the retroperitoneal fat, Roux-en-Y gastric bypass (RYGB) has successfully controlled the disease for 3 years. The clinical presentations and causes of FPLD are reviewed and the role of RYGB is discussed.

[Fasciae latae perforator flap for breast reconstruction: An attractive alternative in case of DIEP contraindication].

PubMed

Lefèvre, M; Sarfati, B; Honart, J-F; Alkashnam, H; Rimareix, F; Leymarie, N; Kolb, F

2017-02-01

The musculocutaneous tensor fascia latae flap was one of the first free flaps described. It is possible to harvest a flap with the same skin paddle, vascularized by a septo-cutaneous perforator running through the tensor fascia lata muscle septum and coming from the ascending branch of the lateral circumflex femoral artery. The DIEP is currently the workhorse of autologous breast reconstruction, but there are some contraindications. The septo-cutaneous tensor fascia latae perforator flap may be an alternative for women with lateral upper thigh lipodystrophy. Between 2010 and 2014, three flaps have been performed in two patients for delayed breast reconstruction (one case of unilateral reconstruction, and one bilateral). Perforators were identified by preoperative angiography. The intervention was performed in a two-team approach, in only one operative position. Perforators were located in the horizontal axis of the upper rim of the pubis bone. One perforator artery was dissected for each flap. The mean caliber of the pedicle was 2.8mm, and the mean length was 6.4cm. The operative time was 240minutes for unilateral flap, 375minutes for bilateral flap. There was no case of total or partial necrosis, or complications on the donor site. Cosmetic results were considered satisfying by patients and surgeons with the reconstructed breast as well as the donor site. Septo-cutaneous fascia lata perforator flap is an attractive flap for breast reconstruction in patients with DIEP contraindication and lateral upper thigh lipodystrophy. It has many advantages: easy to harvest, length and calibre of the pedicle, double team approach, only one operating position, quality of reconstruction. It is necessary to carry out a larger series of cases to study the complication rate in the donor site. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit.

PubMed

Chen, Mao; Yao, Bing; Yang, Qiangbing; Deng, Jichao; Song, Yuning; Sui, Tingting; Zhou, Lina; Yao, HaoBing; Xu, Yuanyuan; Ouyang, Hongsheng; Pang, Daxin; Li, Zhanjun; Lai, Liangxue

2018-04-09

Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous ( FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. © 2018. Published by The Company of Biologists Ltd.

Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals

PubMed Central

Moon, Hyun-Seuk; Dalamaga, Maria; Kim, Sang-Yong; Polyzos, Stergios A.; Hamnvik, Ole-Petter; Magkos, Faidon; Paruthi, Jason

2013-01-01

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes. PMID:23475416

Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy.

PubMed

Guo, Tingqing; Bond, Nichole D; Jou, William; Gavrilova, Oksana; Portas, Jennifer; McPherron, Alexandra C

2012-10-01

Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake.

Do non-nucleoside reverse transcriptase inhibitors contribute to lipodystrophy?

PubMed

Nolan, David

2005-01-01

Lipodystrophy complications, including lipoatrophy (pathological fat loss) and metabolic complications, have emerged as important long-term toxicities associated with antiretroviral therapy in the current era. The wealth of data that has accumulated over the past 6 years has now clarified the contribution of specific antiretroviral drugs to the risk of these clinical endpoints, with evidence that lipoatrophy is strongly associated with the choice of nucleoside reverse transcriptase inhibitor therapy (specifically, stavudine and to a lesser extent zidovudine). The aetiological basis of metabolic complications of antiretroviral therapy has proven to be complex, in that the risk appears to be modulated by a number of lifestyle factors that have made the metabolic syndrome highly prevalent in the general population, with additional contributions from HIV disease status itself, as well as from individual drugs within the HIV protease inhibitor class. The currently licensed non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs, efavirenz and nevirapine, have been proven to have a favourable safety profile in terms of lipodystrophy complications. However, it must be noted that NNRTI drugs also have individual toxicity profiles that must be accounted for when considering and/or monitoring their use in the treatment of HIV infection.

Potential roles for uncoupling proteins in HIV lipodystrophy.

PubMed

Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy

PubMed Central

Guo, Tingqing; Bond, Nichole D.; Jou, William; Gavrilova, Oksana; Portas, Jennifer; McPherron, Alexandra C.

2012-01-01

Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake. PMID:22596054

People living with HIV on ART have accurate perception of lipodystrophy signs: a cross-sectional study.

PubMed

Alencastro, Paulo R; Barcellos, Nemora T; Wolff, Fernando H; Ikeda, Maria Letícia R; Schuelter-Trevisol, Fabiana; Brandão, Ajácio B M; Fuchs, Sandra C

2017-01-13

The prevalence of lipodystrophy ranges from 31 to 65%, depending on the criteria adopted for diagnosis. The usual methods applied in the diagnosis vary from self-perception, medical examination, skinfolds measurements, or even imaging assessment for confirmation of fat distribution changes. Although several methods have been developed, there is no gold standard for characterization of LA and LH, or mixed forms. This study aimed to compare self-reported signs of lipodystrophy with objective measures by skinfolds and circumferences, and to evaluate the prevalence of lipoatrophy (LA) and lipohypertrophy (LH) among subjects living with HIV/AIDS on ART. A cross-sectional study enrolled participants living with HIV/AIDS receiving ART, aged 18 years or older from an outpatient health care center, in Southern Brazil. Self-reported body fat enlargement in the abdomen, chest or breasts, and dorsocervical fat pad were used to determine LH, while LA was identified by self-reported fat wasting of the face, neck, legs, arms or buttocks. Measurements were obtained with a scientific caliper for infraorbital, buccal, and submandibular skinfolds, and using an inelastic tape to measure circumferences of waist, hip, neck, and arm. LH and LA were established by the presence of at least one self-reported sign. Comparisons of self-reported signs with objective measurements for men and women were carried out in 815 participants on ART, out of 1240 participants with HIV infection. Self-report of decreased facial fat and sunken cheeks was associated with lower infraorbital, buccal, and submandibular skinfolds. Participants who reported buffalo hump had, on average, greater neck circumference, as well as those who have increased waist circumference also reported abdominal enlargement, but no buttock wasting. Men were most commonly affected by lipoatrophy (73 vs. 53%; P < 0.001), and women by lipohypertrophy (79 vs. 56%; P < 0.001). In conclusion, self-reported signs of lipodystrophy and lipoatrophy are prevalent, differ by gender, and are associated with objective measurements in people living with HIV/AIDS.

The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity.

PubMed

Morén, Constanza; Juárez-Flores, Diana Luz; Cardellach, Francesc; Garrabou, Glòria

2016-01-01

Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. The aim of this work is to review the potential mitochondrial toxicity derived from drugs used in health care, including anesthetics, antiepileptics, neuroleptics, antidepressants, antivirals, antibiotics, antifungals, antimalarics, antineoplastics, antidiabetics, hypolipemiants, antiarrhythmics, anti-inflammatories and nitric oxide. We herein have reviewed data from experimental and clinical studies to document the molecular mitochondrial basis, potential biomarkers and putative clinical symptoms associated to secondary effects of drugs. One hundred and forty-five articles were selected and the information was organized by means of the primary target to which pharmacologic drugs were directed. Adverse toxic events were classified depending on the mitochondrial offtarget effect and whether they had been demonstrated in the experimental or clinical setting. Since treatment of acquired mitochondriopathies remains supportive and therapeutic interventions cannot be avoided, information of molecular and clinical consequences of toxic exposure becomes fundamental to assess riskbenefit imbalance of treatment prescription. Additionally, there is a crucial need to develop less mitochondrial toxic compounds, novel biomarkers to follow up mitochondrial toxicity (or implement those already proposed) and new approaches to prevent or revert unintended mitochondrial damage.

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

PubMed

Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

2017-01-01

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Compassionate Use Protocol for the Treatment of Autoinflammatory Syndromes

ClinicalTrials.gov

2018-04-17

Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE); Juvenile Dermatomyositis (JDM); Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset During Infancy (SAVI); Aicardi-Goutières Syndrome (AGS)

Genetics Home Reference: congenital generalized lipodystrophy

MedlinePlus

... childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are ... that normally helps to regulate blood sugar levels. Insulin resistance may develop into a more serious disease called ...

75 FR 13559 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... to induce and maintain a reduction of excess visceral abdominal fat in human immunodeficiency virus (HIV)-infected patients with lipodystrophy (a condition in which abnormal deposits of fat are seen...

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report

PubMed Central

2011-01-01

Introduction Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy. Case presentation A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships. Conclusions These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life. PMID:21892961

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report.

PubMed

Mendes, Edmar Lacerda; Ribeiro Andaki, Alynne Christian; Brito, Ciro José; Córdova, Cláudio; Natali, Antônio José; Santos Amorim, Paulo Roberto Dos; de Oliveira, Leandro Licursi; de Paula, Sérgio Oliveira; Mutimura, Eugene

2011-09-05

Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy. A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships. These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life.

Uridine Metabolism in HIV-1-Infected Patients: Effect of Infection, of Antiretroviral Therapy and of HIV-1/ART-Associated Lipodystrophy Syndrome

PubMed Central

Domingo, Pere; Torres-Torronteras, Javier; Pomar, Virginia; Giralt, Marta; Domingo, Joan Carles; Gutierrez, Maria del Mar; Gallego-Escuredo, José M.; Mateo, Maria Gracia; Cano-Soldado, Pedro; Fernandez, Irene; Pastor-Anglada, Marçal; Vidal, Francesc; Villarroya, Francesc; Andreu, Antoni; Marti, Ramon

2010-01-01

Background Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS), although its metabolism in HIV-1-infected patients is poorly understood. Methods Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. Results Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60), and for controls 4.60 µmol/l (IQR: 1.8) (P = 0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein, respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40–4.80) whereas in those with isolated lipoatrophy it was 3.25 (2.55–4.15) µmol/l/l (P = 0.0066). The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. Conclusions HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations. PMID:21085568

Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome.

PubMed

Torriani, Martin; Fitch, Kathleen; Stavrou, Eleni; Bredella, Miriam A; Lim, Ruth; Sass, Christina A; Cypess, Aaron M; Grinspoon, Steven

2012-04-01

The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in lipodystrophic HIV and healthy control subjects. Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [¹⁸F]FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. Mean standardized uptake value of [¹⁸F]FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r² = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure.

Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.

PubMed

Agarwal, Anil K; Tunison, Katie; Dalal, Jasbir S; Nagamma, Sneha S; Hamra, F Kent; Sankella, Shireesha; Shao, Xinli; Auchus, Richard J; Garg, Abhimanyu

2017-11-01

Defects in the biosynthesis of phospholipids and neutral lipids are associated with cell membrane dysfunction, disrupted energy metabolism, and diseases including lipodystrophy. In these pathways, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) enzymes transfer a fatty acid to the sn-2 carbon of sn-1-acylglycerol-3-phosphate (lysophosphatidic acid) to form sn-1, 2-acylglycerol-3-phosphate [phosphatidic acid (PA)]. PA is a precursor for key phospholipids and diacylglycerol. AGPAT1 and AGPAT2 are highly homologous isoenzymes that are both expressed in adipocytes. Genetic defects in AGPAT2 cause congenital generalized lipodystrophy, indicating that AGPAT1 cannot compensate for loss of AGPAT2 in adipocytes. To further explore the physiology of AGPAT1, we characterized a loss-of-function mouse model (Agpat1-/-). The majority of Agpat1-/- mice died before weaning and had low body weight and low plasma glucose levels, independent of plasma insulin and glucagon levels, with reduced percentage of body fat but not generalized lipodystrophy. These mice also had decreased hepatic messenger RNA expression of Igf-1 and Foxo1, suggesting a decrease in gluconeogenesis. In male mice, sperm development was impaired, with a late meiotic arrest near the onset of round spermatid production, and gonadotropins were elevated. Female mice showed oligoanovulation yet retained responsiveness to gonadotropins. Agpat1-/- mice also demonstrated abnormal hippocampal neuron development and developed audiogenic seizures. In summary, Agpat1-/- mice developed widespread disturbances of metabolism, sperm development, and neurologic function resulting from disrupted phospholipid homeostasis. AGPAT1 appears to serve important functions in the physiology of multiple organ systems. The Agpat1-deficient mouse provides an important model in which to study the contribution of phospholipid and triacylglycerol synthesis to physiology and diseases. Copyright © 2017 Endocrine Society.

Severity of Lipodystrophy Is Associated with Decreased Health-Related Quality of Life

PubMed Central

Murri, Rita; Orlando, Gabriella; Giovanardi, Chiara; Squillace, Nicola; Vandelli, Marcella; Beghetto, Barbara; Nardini, Giulia; De Paola, Maria; Esposito, Roberto; Wu, Albert W.

2008-01-01

Abstract The impact of lipodystrophy (LD) on quality of life is high, but it has not been demonstrated in literature. The objective of the study was to assess the impact of LD on the health–related quality of life (HRQOL) in HIV-infected people on highly active antiretroviral therapy (HAART). Patients with LD phenotype defined by the Multicenter AIDS Cohort Study (MACS) were included. Three different methods were used to define LD severity: both patient and physician evaluation using the HIV Outpatient Study (HOPS) severity scales and the Lipodystrophy Case Definition (LDCD). The HRQOL was evaluated by MOS-HIV Health Survey. Four hundred one patients on HAART for a mean of 108 ± 52 months were evaluated for LD at the Metabolic Clinic of Modena and Reggio Emilia University were enrolled from January 2003 to July 2006. According to self-perceived or physician-based HOPS, 106 (26.5%) and 122 (30.4%) patients had severe LD. Females had significantly more severe LD. Few HRQOL scores correlated to LD severity using the physician-based score (both HOPSph and LDCD), while all the HRQOL scores correlated with LD severity when a patient-based score was used (HOPSpt). In multiple linear regression analysis, Mental Health HRQOL score, gender, body mass index, age, body image satisfaction were independent predictors of patient-based (HOPSpt) LD, while none of the HRQOL scores, but female gender, age, waist-to-hip ratio, limb fat, and body image satisfaction were correlated with physician-estimated HOPSph LD severity. HRQOL was strongly correlated with LD severity when a patient-based score was used. For an overall assessment of the impact of LD on HIV-infected people, both patient-based and physician-based measures are required. PMID:18647097

The role of diet, exercise and smoking in dyslipidaemia in HIV-infected patients with lipodystrophy.

PubMed

Shah, M; Tierney, K; Adams-Huet, B; Boonyavarakul, A; Jacob, K; Quittner, C; Dinges, Wl; Peterson, D; Garg, A

2005-07-01

Lipodystrophy in HIV-infected (LDHIV) patients receiving protease inhibitors (PIs) is associated with dyslipidaemia. Whether lifestyle factors play a role in dyslipidaemia in LDHIV subjects on PIs is not well characterized. A total of 45 LDHIV male and six LDHIV female patients on PIs were recruited, and data were collected on smoking, exercise, diet (by 3-day food record), and fasting levels of serum lipids and lipoproteins. The relationships between lifestyle factors and metabolic variables were analysed in male patients by Spearman's correlation test and the significant relationships were further analysed by adjusting for age, PI duration, and waist circumference by Spearman's partial correlation test. In men, mean (+/-standard deviation) serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C were 212+/-70, 35+/-7.3, 325+/-230 and 169+/-44 mg/dL, respectively. Sixty-seven percent of the men exercised regularly and 31.1% smoked. The reported diet was high in cholesterol (390+/-212 mg) and percentage energy from saturated (12.2+/-3.3%) and trans (2.4+/-1.2%) fats, and low in soluble fibre (6.9+/-2.3 g) compared with recent dietary guidelines. Following adjustments for the confounding variables, percentage energy intake from total protein and animal protein was positively related to TC (r=0.44, P<0.01 and r=0.37, P<0.05, respectively), TG (r=0.40, P<0.01 and r=0.46, P<0.01, respectively) and non-HDL-C (r=0.56, P<0.001 and r=0.49, P<0.01, respectively), that from trans fat was positively related to TG (r=0.34, P<0.05), and soluble fibre was negatively related to non-HDL-C (r=-0.41, P<0.01). Moderate to heavy aerobic exercise tended to be associated with higher HDL-C (r=0.30, P=0.07) whereas smoking was not associated with any of the metabolic variables. Increased intake of total protein, animal protein and trans fat, and reduced soluble fibre consumption contribute to dyslipidaemia in LDHIV subjects on PIs.

Identification of a novel nonsense mutation and a missense substitution in the AGPAT2 gene causing congenital generalized lipodystrophy type 1

PubMed Central

Haghighi, Amirreza; Razzaghy-Azar, Maryam; Talea, Ali; Sadeghian, Mahnaz; Ellard, Sian; Haghighi, Alireza

2012-01-01

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disease characterized by the generalized scant of adipose tissue. CGL type 1 is caused by mutations in gene encoding 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2). A clinical and molecular genetic investigation was performed in affected and unaffected members of two families with CGL type 1. The AGPAT2 coding region was sequenced in index cases of the two families. The presence of the identified mutations in relevant parents was tested. We identified a novel nonsense mutation (c.685G>T, p.Glu229*) and a missense substitution (c.514G>A, p.Glu172Lys). The unaffected parents in both families were heterozygous carrier of the relevant mutation. The results expand genotype–phenotype spectrum in CGL1 and will have applications in prenatal and early diagnosis of the disease. This is the first report of Persian families identified with AGPAT2 mutations. PMID:22902344

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease.

PubMed

Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K; Saudek, Vladimir; O'Rahilly, Stephen; Walther, Tobias C; Barroso, Inês; Savage, David B

2014-06-17

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

PubMed Central

Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J.; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K.; Saudek, Vladimir; O’Rahilly, Stephen; Walther, Tobias C.; Barroso, Inês; Savage, David B.

2014-01-01

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action. PMID:24889630

Evidence-based treatment for gynoid lipodystrophy: A review of the recent literature.

PubMed

Pérez Atamoros, Francisco M; Alcalá Pérez, Daniel; Asz Sigall, Daniel; Ávila Romay, Alfonsina A; Barba Gastelum, José A; de la Peña Salcedo, José A; Escalante Salgado, Pablo E; Gallardo Palacios, Guillermo J; Guerrero-Gonzalez, Guillermo A; Morales De la Cerda, Rodrigo; Ponce Olivera, Rosa María; Rossano Soriano, Fabiola; Solís Tinoco, Eduardo; Welsh Hernández, Esperanza C

2018-04-30

Gynoid lipodystrophy (GLD) is a structural, inflammatory, and biochemical disorder of the subcutaneous tissue causing alterations in the topography of the skin. Commonly known as "cellulite," GLD affects up to 90% of women, practically in all stages of the life cycle, beginning in puberty. It is a clinical condition that considerably affects the patients' quality of life. It is a frequent reason for consultation, although the patients resort to empirical, improvised, nonevidence-based treatments which discourage and can be a source of frustration not only because of the lack of results but also due to the complications derived from those treatments. In this article, a panel of experts from different specialties involved in the management of this clinical skin disorder presents the results of a systematic literature search and of the consensus discussion of the evidence obtained from different treatments currently available. The analysis was divided into topical, systemic, noninvasive, and minimally invasive treatments. © 2018 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.

Partial volume correction of magnetic resonance spectroscopic imaging

NASA Astrophysics Data System (ADS)

Lu, Yao; Wu, Dee; Magnotta, Vincent A.

2007-03-01

The ability to study the biochemical composition of the brain is becoming important to better understand neurodegenerative and neurodevelopmental disorders. Magnetic Resonance Spectroscopy (MRS) can non-invasively provide quantification of brain metabolites in localized regions. The reliability of MRS is limited in part due to partial volume artifacts. This results from the relatively large voxels that are required to acquire sufficient signal-to-noise ratios for the studies. Partial volume artifacts result when a MRS voxel contains a mixture of tissue types. Concentrations of metabolites vary from tissue to tissue. When a voxel contains a heterogeneous tissue composition, the spectroscopic signal acquired from this voxel will consist of the signal from different tissues making reliable measurements difficult. We have developed a novel tool for the estimation of partial volume tissue composition within MRS voxels thus allowing for the correction of partial volume artifacts. In addition, the tool can localize MR spectra to anatomical regions of interest. The tool uses tissue classification information acquired as part of a structural MR scan for the same subject. The tissue classification information is co-registered with the spectroscopic data. The user can quantify the partial volume composition of each voxel and use this information as covariates for metabolite concentrations.

Haplotypes in the promoter region of the CIDEC gene associated with growth traits in Nanyang cattle

USDA-ARS?s Scientific Manuscript database

Cell death-inducing DFFA-like effector c (CIDEC, also known as Fsp27) has emerged as an important regulator of metabolism associated with lipodystrophy, diabetes, and hepatic steatosis. It is required for unilocular lipid droplet formation and optimal energy storage. The mechanism between this gene ...

Disruption of the Arabidopsis CGI-58 homologue produces Chanarin-Dorfman-like lipodystrophy in plants

USDA-ARS?s Scientific Manuscript database

CGI-58 is the defective gene in the human neutral lipid storage disease called Chanarin-Dorfman syndrome. This disorder causes intracellular lipid droplets to accumulate in nonadipose tissues, such as skin and blood cells. Here, disruption of the homologous CGI-58 gene in Arabidopsis thaliana result...

Arabidopsis SEIPIN proteins modulate triacylglycerol accumulation and influence lipid droplet proliferation

USDA-ARS?s Scientific Manuscript database

The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. By contrast to the single SEIPIN genes in humans and yeast, there are three SEIPIN homologues in Arabidopsis thaliana, designated At-SEIPIN1, At-SEIPIN2 and At-SEIPIN3. Here, a yeast (Saccharomy...

Factors associated with severe impact of lipodystrophy on the quality of life of patients infected with HIV-1.

PubMed

Blanch, Jordi; Rousaud, Araceli; Martinez, Esteban; De Lazzari, Elisa; Milinkovic, Ana; Peri, Josep-Maria; Blanco, José-Luis; Jaen, Jesús; Navarro, Victor; Massana, Guillem; Gatell, Josep-Maria

2004-05-15

A standardized questionnaire was used to assess the impact of lipodystrophy (LD) on quality of life (QoL). Eighty-four consecutive asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected outpatients with clinical LD completed a modified version of the Dermatology Life Quality Index (DLQI) survey to measure the impact of body fat changes on their QoL. Body changes influenced dressing for 55 patients (65%), produced feelings of shame for 41 (49%), and disrupted sexual life for 23 (27%). There was a greater impact on the DLQI due to body changes among women, injection drug users, patients with abdominal or breast lipoaccumulation, and patients with a high number of non-LD side effects. Multivariate proportional odds model analysis showed that the severity of non-LD-associated side effects and the presence of breast lipoaccumulation were associated with impaired psychosocial functioning. Specific characteristics of patients, antiretroviral-based side effects, and breast lipoaccumulation exert a greater impact on QoL in HIV-1-infected patients with LD.

[Bezafibrate in an infant with congenital generalized lipodystrophy and severe hypertriglyceridemia].

PubMed

Araújo, Rogério Santiago; Ramos, André de Paula Silva; Borges, Máriton de Araújo Sousa

2013-11-01

Congenital generalized lipodystrophy (CGL) with severe hypertriglyceridemia in a children less than 1 year of age is associated with worse metabolic risk. We used data from patient records, as well as extensive literature research to write the manuscript. We report the case of an infant with typical phenotype of CGL and hypertriglyceridemia of 1,360 mg/dL who was treated with bezafibrate at a dose of 30 to 60 mg/day from age 11 months to 5.5 years old, with a measurement of nadir of triglycerides of 55 mg/dL. Clinical evolution and clinical laboratory tests before and after bezafibrate were carried out over 5 years and 6 months. Phenotype was classified as CGL type 2. Despite the efficient control of hypertriglyceridemia and absence of development of diabetes mellitus, the use of bezafibrate did not prevent the onset of hepatic steatosis during evolution. Hypolipidemic therapy with bezafibrate proved effective in maintaining the levels of triglycerides, cholesterol and its fractions at normal levels, and its use was not correlated with severe side effects during the described period.

13 CFR 107.880 - Assets acquired in liquidation of Portfolio securities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Portfolio securities. 107.880 Section 107.880 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... liquidation of Portfolio securities. You may acquire assets in full or partial liquidation of a Small Business... assets. You must dispose of assets acquired in liquidation of a Portfolio security within a reasonable...

Early lexical and phonological acquisition and its relationships.

PubMed

Wiethan, Fernanda Marafiga; Nóro, Letícia Arruda; Mota, Helena Bolli

2014-01-01

Verifying likely relationships between lexical and phonological development of children aged between 1 year to 1 year, 11 months and 29 days, who were enrolled in public kindergarten schools of Santa Maria (RS). The sample consisted of 18 children of both genders, with typical language development and aged between 1 year to 1 year, 11 months and 29 days, separated in three age subgroups. Visual recordings of spontaneous speech of each child were collected and then lexical analysis regarding the types of the said lexical items and phonological assessment were performed. The number of sounds acquired and partially acquired were counted together, and the 19 sounds and two all phones of Brazilian Portuguese were considered. To the statistical analysis, the tests of Kruskal-Wallis and Wilcoxon were used, with significance level of prelace_LT0.05. When compared the means relating to the acquired sounds and mean of the acquired and partially acquired sounds percentages, there was difference between the first and the second age subgroup, and between the first and the third subgroup. In the comparison of the said lexical items means among the age subgroups, there was difference between the first and the second subgroup, and between the first and the third subgroup again. In the comparison between the said lexical items and acquired and partially acquired sounds in each age subgroup, there was difference only in the age subgroup of 1 year and 8 months to 1 year, 11 months and 29 days, in which the sounds highlighted. The phonological and lexical domains develop as a growing process and influence each other. The Phonology has a little advantage.

Noncosmetic applications of liposuction.

PubMed

Coleman, W P

1988-10-01

Noncosmetic applications of liposuction have continued to appear since its introduction into the United States in 1982. Although the most common use is in removing lipomas, liposuction has also been used for benign symmetric lipomatosis, flap undermining, flap defatting, gynecomastia, pseudogynecomastia, breast reduction, buffalo hump, hypertrophic insulin lipodystrophy, lymphedema, evacuating hematomas, emergency neck defatting for airway restoration, and axillary hyperhidrosis. Other uses remain to be discovered.

Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy

PubMed Central

Shimomura, Iichiro; Hammer, Robert E.; Richardson, James A.; Ikemoto, Shinji; Bashmakov, Yuriy; Goldstein, Joseph L.; Brown, Michael S.

1998-01-01

Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPα, PPARγ, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFα were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans. PMID:9784493

Association of APOC3 polymorphisms with both dyslipidemia and lipoatrophy in HAART-receiving patients.

PubMed

Bonnet, Eric; Bernard, Jacques; Fauvel, Josette; Massip, Patrice; Ruidavets, Jean-Bernard; Perret, Bertrand

2008-02-01

The incidence and the magnitude of lipodystrophy and dyslipidemia in HIV-treated people reported in previous studies are very variable. Several predisposing factors have been identified, but there are few data on genetic factors. To search for a correlation between APOC3 polymorphisms and lipid disorders and lipodystrophy in HIV patients under d4T and protease inhibitors (PI)-containing HAART, we designed a monocenter, cross-sectional study in a University Hospital in Southern France during the period 2001-2004. Forty patients under HAART were included, with d4T for > or = 2 years and PI for > or = 1 year. We determined body mass composition by DXA, lipoprotein markers, and the -455/-482 apo C3 genotypes. Carriers of APOC3 variant alleles (-455 1/-482 1) displayed higher levels of triglycerides (3.72 vs. 2.57 mmol/liter), apo C3 (45.3 vs. 34.5 mg/liter), and apo E (130.2 vs. 66.5 mg/liter) and a lower fat mass (13.9 vs. 19.7%) than patients with nonvariant alleles (-455 0/-482 0). APOC3 polymorphisms might be associated with both dyslipidemia and lipoatrophy in HAART-treated patients.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

PubMed

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia.

PubMed

Wierzbicki, Anthony S; Viljoen, Adie

2016-09-01

Anti-sense oligonucleotide (ASO) therapies are a new development in clinical pharmacology offering greater specificity compared to small molecule inhibitors and the ability to target intracellular process' not susceptible to antibody-based therapies. This article reviews the chemical biology of ASOs and related RNA therapeutics. It then reviews the data on their use to treat hyperlipidaemia. Data on mipomersen - an ASO to apolipoprotein B-100(apoB) licensed for treatment of homozygous familial hypercholesterolaemia (FH) is presented. Few effective therapies are available to reduce atehrogenic lipoprotein (a) levels. An ASO therapy to apolipoprotein(a) (ISIS Apo(a)Rx) specifically reduced lipoprotein (a) levels by up to 78%. Treatment options for patients with familial chylomicronaemia syndrome (lipoprotein lipase deficiency; LPLD) or lipodystrophies are highly limited and often inadequate. Volanesorsen, an ASO to apolipoprotein C-3, shows promise in the treatment of LPLD and severe hypertriglyceridaemia as it increases clearance of triglyceride-rich lipoproteins and can normalise triglycerides in these patients. The uptake of the novel ASO therapies is likely to be limited to selected niche groups or orphan diseases. These will include homozygous FH, severe heterozygous FH for mipomersen; LPLD deficiency and lipodystrophy syndromes for volanesorsen and treatment of patients with high elevated Lp(a) levels.

Replicating and Extending Research on the Partial Assignment Completion Effect: Is Sunk Cost Related to Partial Assignment Completion Strength?

ERIC Educational Resources Information Center

Hawthorn-Embree, Meredith L.; Taylor, Emily P.; Skinner, Christopher H.; Parkhurst, John; Nalls, Meagan L.

2014-01-01

After students acquire a skill, mastery often requires them to choose to engage in assigned academic activities (e.g., independent seatwork, and homework). Although students may be more likely to choose to work on partially completed assignments than on new assignments, the partial assignment completion (PAC) effect may not be very powerful. The…

Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

PubMed

Gilbert, Frédéric; Focquaert, Farah

2015-01-01

This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oligosaccharide composition is similar in drusen and dense deposits in membranoproliferative glomerulonephritis type II.

PubMed

D'souza, Yvonne B; Jones, Carolyn J P; Short, Colin D; Roberts, Ian S D; Bonshek, Richard E

2009-04-01

Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.

Atypical Progeroid Syndrome due to Heterozygous Missense LMNA Mutations

PubMed Central

Garg, Abhimanyu; Subramanyam, Lalitha; Agarwal, Anil K.; Simha, Vinaya; Levine, Benjamin; D'Apice, Maria Rosaria; Novelli, Giuseppe; Crow, Yanick

2009-01-01

Context: Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia are well-recognized allelic autosomal dominant and recessive progeroid disorders, respectively, due to mutations in lamin A/C (LMNA) gene. Heterozygous LMNA mutations have also been reported in a small number of patients with a less well-characterized atypical progeroid syndrome (APS). Objective: The objective of the study was to investigate the underlying genetic and molecular basis of the phenotype of patients presenting with APS. Results: We report 11 patients with APS from nine families, many with novel heterozygous missense LMNA mutations, such as, P4R, E111K, D136H, E159K, and C588R. These and previously reported patients now reveal a spectrum of clinical features including progeroid manifestations such as short stature, beaked nose, premature graying, partial alopecia, high-pitched voice, skin atrophy over the hands and feet, partial and generalized lipodystrophy with metabolic complications, and skeletal anomalies such as mandibular hypoplasia and mild acroosteolysis. Skin fibroblasts from these patients when assessed for lamin A/C expression using epifluorescence microscopy revealed variable nuclear morphological abnormalities similar to those observed in patients with HGPS. However, these nuclear abnormalities in APS patients could not be rescued with 48 h treatment with farnesyl transferase inhibitors, geranylgeranyl transferase inhibitors or trichostatin-A, a histone deacetylase inhibitor. Immunoblots of cell lysates from fibroblasts did not reveal prelamin A accumulation in any of these patients. Conclusions: APS patients have a few overlapping but some distinct clinical features as compared with HGPS and mandibuloacral dysplasia. The pathogenesis of clinical manifestations in APS patients seems not to be related to accumulation of mutant farnesylated prelamin A. PMID:19875478

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels.

PubMed

López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Ma; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R

2015-01-01

Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student's t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001-0.521, p = 0.027). HALS is associated with decreased sTWEAK levels.

Lipodystrophy in HIV patients: its challenges and management approaches.

PubMed

Singhania, Rohit; Kotler, Donald P

2011-01-01

HIV-associated lipodystrophy is a term used to describe a constellation of body composition (lipoatrophy and lipohypertrophy) and metabolic (dyslipidemia and insulin resistance) alterations that accompany highly active antiretroviral therapy. These changes, which resemble metabolic syndrome, have been associated with a variety of adverse outcomes including accelerated cardiovascular disease. The body composition and metabolic changes appear to cluster in HIV infection, although they are distinct alterations and do not necessarily coexist. Epidemiological studies have demonstrated multiple pathogenic influences associated with host, disease, and treatment-related factors. The adverse treatment effects were more prominent in early regimens; continued drug development has led to the application of metabolically safer regimens with equal or greater potency than the regimens being replaced. Disease-related factors include HIV infection as well as inflammation, immune activation, and immune depletion. The body composition changes promote anxiety and depression in patients and may affect treatment adherence. Treatment of dyslipidemia and alterations in glucose metabolism is the same as in non-HIV-infected individuals. Lipoatrophy is managed by strategic choice of antivirals or by antiviral switching, and in some cases by plastic/reconstructive surgery. Lipohypertrophy has been managed mainly by lifestyle modification, ie, a hypocaloric diet and increased exercise. A growth hormone releasing factor, which reduces central fat, has recently become available for clinical use.

Lipodystrophy in HIV patients: its challenges and management approaches

PubMed Central

Singhania, Rohit; Kotler, Donald P

2011-01-01

HIV-associated lipodystrophy is a term used to describe a constellation of body composition (lipoatrophy and lipohypertrophy) and metabolic (dyslipidemia and insulin resistance) alterations that accompany highly active antiretroviral therapy. These changes, which resemble metabolic syndrome, have been associated with a variety of adverse outcomes including accelerated cardiovascular disease. The body composition and metabolic changes appear to cluster in HIV infection, although they are distinct alterations and do not necessarily coexist. Epidemiological studies have demonstrated multiple pathogenic influences associated with host, disease, and treatment-related factors. The adverse treatment effects were more prominent in early regimens; continued drug development has led to the application of metabolically safer regimens with equal or greater potency than the regimens being replaced. Disease-related factors include HIV infection as well as inflammation, immune activation, and immune depletion. The body composition changes promote anxiety and depression in patients and may affect treatment adherence. Treatment of dyslipidemia and alterations in glucose metabolism is the same as in non-HIV-infected individuals. Lipoatrophy is managed by strategic choice of antivirals or by antiviral switching, and in some cases by plastic/reconstructive surgery. Lipohypertrophy has been managed mainly by lifestyle modification, ie, a hypocaloric diet and increased exercise. A growth hormone releasing factor, which reduces central fat, has recently become available for clinical use. PMID:22267946

Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

PubMed

Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

2013-12-01

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

Treatment of facial lipoatrophy with polymethylmethacrylate among patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): impact on the quality of life.

PubMed

Quintas, Rodrigo C S; de França, Emmanuel R; de Petribú, Kátia C L; Ximenes, Ricardo A A; Quintas, Lóren F F M; Cavalcanti, Ernando L F; Kitamura, Marco A P; Magalhães, Kássia A A; Paiva, Késsia C F; Filho, Demócrito B Miranda

2014-04-01

The lipodystrophy syndrome is characterized by selective loss of subcutaneous fat on the face and extremities (lipoatrophy) and/or accumulation of fat around the neck, abdomen, and thorax (lipohypertrophy). The aim of this study has been to assess the impact of polymethylmethacrylate facial treatment on quality of life, self-perceived facial image, and the severity of depressive symptoms in patients living with HIV/AIDS. A non-randomized before and after interventional study was developed. Fifty-one patients underwent facial filling. The self-perceived quality of life, facial image, and degree of depressive symptoms were measured by the Short-Form 36 and HIV/AIDS--Targeted quality of life questionnaires, by a visual analogue scale and by the Beck depression inventory, respectively, before and three months after treatment. Six of the eight domains of Short-Form 36 and eight of the nine dimensions of the HIV/AIDS--Targeted quality of life questionnaires, together with the visual analogue scale and by the Beck depression inventory scores, revealed a statistically significant improvement. The only adverse effects registered were edema and ecchymosis. The treatment of facial lipoatrophy improved the self-perceived quality of life and facial image as well as any depressive symptoms among patients with HIV/AIDS. © 2014 The International Society of Dermatology.

48 CFR 49.603-2 - Fixed-price contracts-partial termination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... certifies that all contract termination inventory (including scrap) has been retained or acquired by the... stating (i) that all subcontract termination inventory (including scrap) has been retained or acquired by... certifies that all items of termination inventory, the costs of which were used in arriving at the amount of...

Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1

PubMed Central

Goldbach-Mansky, R

2012-01-01

The disease-based discovery of the molecular basis for autoinflammatory diseases has led not only to a rapidly growing number of clinically and genetically identifiable disorders, but has unmantled key inflammatory pathways such as the potent role of the alarm cytokine interleukin (IL)-1 in human disease. Following its initial failures in the treatment of sepsis and the moderate success in the treatment of rheumatoid arthritis, IL-1 blocking therapies had a renaissance in the treatment of a number of autoinflammatory conditions, and IL-1 blocking therapies have been Food and Drug Administration (FDA)-approved for the treatment of the autoinflammatory conditions: cryopyrin-associated periodic syndromes (CAPS). CAPS and deficiency of the IL-1 receptor antagonist (DIRA), both genetic conditions with molecular defects in the IL-1 pathway, have provided a pathogenic rationale to IL-1 blocking therapies, and the impressive clinical results confirmed the pivotal role of IL-1 in human disease. Furthermore, IL-1 blocking strategies have shown clinical benefit in a number of other genetically defined autoinflammatory conditions, and diseases with clinical similarities to the monogenic disorders and not yet identified genetic causes. The discovery that IL-1 is not only triggered by infectious danger signals but also by danger signals released from metabolically ‘stressed’ or even dying cells has extended the concept of autoinflammation to disorders such as gout, and those that were previously not considered inflammatory, such as type 2 diabetes, coronary artery disease, obesity and some degenerative diseases, and provided the conceptual framework to target IL-1 in these diseases. Despite the tremendous success of IL-1 blocking therapy, the use of these agents in a wider spectrum of autoinflammatory conditions has uncovered disease subsets that are not responsive to IL-1 blockade, including the recently discovered proteasome-associated autoinflammatory syndromes such as chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperatures (CANDLE), Japanese autoinflammatory syndrome with lipodystrophy (JASL), Nakajo–Nishimura syndrome (NNS) and joint contractures, muscle atrophy, panniculitis induced lipodystrophy (JMP), and urge the continued quest to characterize additional dysregulated innate immune pathways that cause autoinflammatory conditions. PMID:22288582

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

PubMed

Tsuchiya, Naho; Pathipvanich, Panita; Wichukchinda, Nuanjun; Rojanawiwat, Archawin; Auwanit, Wattana; Ariyoshi, Koya; Sawanpanyalert, Pathom

2014-10-30

Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand. All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models. Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification. HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia.

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

PubMed Central

López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Mª; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R.

2015-01-01

Background and Objectives Obesity and HIV-1/HAART–associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. Methods This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student’s t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Results Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001–0.521, p = 0.027). Conclusions HALS is associated with decreased sTWEAK levels. PMID:26658801

Treatment of altered body composition in HIV-associated lipodystrophy: comparison of rosiglitazone, pravastatin, and recombinant human growth hormone.

PubMed

Macallan, Derek C; Baldwin, Christine; Mandalia, Sundihya; Pandol-Kaljevic, Vjera; Higgins, Nadine; Grundy, Alan; Moyle, Graeme J

2008-01-01

Treatment options for HIV-associated lipodystrophy syndrome (HALS) remain limited. The objective of this randomized open-label study was to compare three emerging therapies, rosiglitazone, pravastatin, and growth hormone alone and together, in men and women with HALS. Sixty-four subjects received daily rosiglitazone (4 mg, n = 14), pravastatin (40 mg, n = 11), or rosiglitazone plus pravastatin (n = 13) for 48 weeks or recombinant human growth hormone (rhGH; Serostim 2 mg, 12 weeks, n = 13) alone or combined with rosiglitazone (n = 13). Primary endpoint was body composition change by dual X-ray absorptiometry (DXA) and computed tomography (CT). Rosiglitazone resulted in slow accrual of limb fat detected by DXA (+444 +/- 186 g; p < .05) but not CT. Pravastatin had no consistent significant effects on body composition, although it reduced total and LDL cholesterol. Negative interactions were observed between pravastatin and rosiglitazone. rhGH reduced abdominal fat by CT (-31 +/- 15 cm2, 26%; p < .05) and DXA (-1597 +/- 383 g, 27%; p < .05) and increased trunk and limb lean mass (+10% and +12%, respectively). However, effects largely disappeared within 12 weeks post treatment. rhGH alone impaired insulin sensitivity but not when combined with rosiglitazone. Prolonged rosiglitazone treatment slowly improves lipoatrophy. rhGH rapidly and selectively reduces visceral fat, although effects are short-lived; co-administered rosiglitazone abrogates rhGH-related insulin resistance.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications

PubMed Central

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A.; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C. Ronald

2014-01-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75–81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications.—Vernochet, C., Damilano, F., Mourier, A., Bezy, O., Mori, M. A., Smyth, G., Rosenzweig, A., Larsson, N.-G., Kahn, C. R. Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications. PMID:25005176

Prospective study of a community reintegration programme for patients with acquired chronic brain injury: effects on caregivers' emotional burden and family functioning.

PubMed

Geurtsen, Gert J; van Heugten, Caroline M; Meijer, Ron; Martina, Juan D; Geurts, Alexander C H

2011-01-01

To examine the effects of a residential community reintegration programme for patients with psychosocial problems due to acquired chronic brain injury on caregivers' emotional burden and family functioning. A prospective cohort study with waiting list control and 1-year follow-up. Forty-one caregivers of which 28 female. Mean age was 48 ± 8.3 years and 33 caregivers were parents. A structured residential treatment programme was offered to the patients directed at domestic life, work, leisure time and social interactions. The Involvement Evaluation Questionnaire for Brain Injury (IEQ-BI) for emotional burden, the General Health Questionnaire (GHQ) for psychological health and the Family Assessment Device (FAD) for family functioning were used. There was an overall significant effect of Time for all outcome measures (MANOVA T(2 )= 9.1, F(15,317) = 64.1, p = 0.000). The effect sizes were moderate for three IEQ-BI sub-scales (partial η(2 )= 0.12-0.17) and small for two sub-scales (partial η(2 )= 0.05-0.09). The effect size for GHQ was moderate (partial η(2 )= 0.11). As for FAD no significant time effects were present (partial η(2 )= 0.00-0.04). Emotional burden and psychological health of the caregivers improved significantly when patients with acquired brain injury and psychosocial problems followed a residential community reintegration programme. Family dynamics remained stable.

Leptin in humans: lessons from translational research.

PubMed

Blüher, Susann; Mantzoros, Christos S

2009-03-01

Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects with complete (congenital) leptin deficiency caused by mutations in the leptin gene as well as in humans with relative leptin deficiency, including states of lipoatrophy or negative energy balance and neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in states of exercise-induced weight loss. In those conditions, most neuroendocrine, metabolic, or immune disturbances can be restored by leptin administration. Leptin replacement therapy is thus a promising approach in several disease states, including congenital complete leptin deficiency, states of energy deprivation, including anorexia nervosa or milder forms of hypothalamic amenorrhea, as well as syndromes of insulin resistance seen in conditions such as congenital or acquired lipodystrophy. In contrast, states of energy excess such as garden-variety obesity are associated with hyperleptinemia that reflects either leptin tolerance or leptin resistance. For those conditions, development of leptin sensitizers is currently a focus of pharmaceutical research. This article summarizes our current understanding of leptin's role in human physiology and its potential role as a novel therapeutic option in human disease states associated with a new hormone deficiency, ie, leptin deficiency.

Comparing Efficacy and Costs of Four Facial Fillers in Human Immunodeficiency Virus-Associated Lipodystrophy: A Clinical Trial.

PubMed

Vallejo, Alfonso; Garcia-Ruano, Angela A; Pinilla, Carmen; Castellano, Michele; Deleyto, Esther; Perez-Cano, Rosa

2018-03-01

The objective of this study was to evaluate and compare the safety and effectiveness of four different dermal fillers in the treatment of facial lipoatrophy secondary to human immunodeficiency virus. The authors conducted a clinical trial including 147 patients suffering from human immunodeficiency virus-induced lipoatrophy treated with Sculptra (poly-L-lactic acid), Radiesse (calcium hydroxylapatite), Aquamid (polyacrylamide), or autologous fat. Objective and subjective changes were evaluated during a 24-month follow-up. Number of sessions, total volume injected, and overall costs of treatment were also analyzed. A comparative cost-effectiveness analysis of the treatment options was performed. Objective improvement in facial lipoatrophy, assessed by the surgeon in terms of changes from baseline using the published classification of Fontdevila, was reported in 53 percent of the cases. Patient self-evaluation showed a general improvement after the use of facial fillers. Patients reported being satisfied with the treatment and with the reduced impact of lipodystrophy on their quality of life. Despite the nonsignificant differences observed in the number of sessions and volume, autologous fat showed significantly lower costs than all synthetic fillers (p < 0.05). Surgical treatment of human immunodeficiency virus-associated facial lipoatrophy using dermal fillers is a safe and effective procedure that improves the aesthetic appearance and the quality of life of patients. Permanent fillers and autologous fat achieve the most consistent results over time, with lipofilling being the most cost-effective procedure.

Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints.

PubMed

Rodríguez, Alexander J; Neeman, Teresa; Giles, Aaron G; Mastronardi, Claudio A; Paz Filho, Gilberto

2014-11-01

The clinical manifestations of lipodystrophy syndromes (LS) are hypoleptinemia, hyperglycemia, insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving these pathologies. Currently, there are no data compiling the evidence from the literature, and demonstrating the effect of LRT in LS patients. A systematic review of the MEDLINE and Cochrane Library databases was conducted to identify studies assessing the effect of LRT on metabolic and hepatic endpoints in patients with LS not associated with highly active antiretroviral therapy (HAART) use. Standardized mean differences (SMD) and 95% confidence intervals of pooled results were calculated for overall changes in glucose homeostasis, lipid profile, and hepatic physiology, using an inverse-variance random-effects model. After screening, 12 studies were included for review. Meta-analysis of results from 226 patients showed that LRT decreased fasting glucose [0.75 SMD units (range 0.36-1.13), p=0.0001], HbA1c [0.49 (0.17-0.81), p=0.003], triglycerides [1.00 (0.69-1.31), p<0.00001], total cholesterol [0.62 (0.21-1.02), p=0.003], liver volume [1.06 (0.51-1.61), p=0.0002] and AST [0.41 (0.10-0.73) p=0.01]. In patients with non-HAART LS, LRT improves the outcome of several metabolic and hepatic parameters. Studies were limited by small populations and therefore large prospective trials are needed to validate these findings.

Mechanisms of insulin resistance in obesity

PubMed Central

Ye, Jianping

2014-01-01

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

Mathematical modeling of diphtheria transmission in Thailand.

PubMed

Sornbundit, Kan; Triampo, Wannapong; Modchang, Charin

2017-08-01

In this work, a mathematical model for describing diphtheria transmission in Thailand is proposed. Based on the course of diphtheria infection, the population is divided into 8 epidemiological classes, namely, susceptible, symptomatic infectious, asymptomatic infectious, carrier with full natural-acquired immunity, carrier with partial natural-acquired immunity, individual with full vaccine-induced immunity, and individual with partial vaccine-induced immunity. Parameter values in the model were either directly obtained from the literature, estimated from available data, or estimated by means of sensitivity analysis. Numerical solutions show that our model can correctly describe the decreasing trend of diphtheria cases in Thailand during the years 1977-2014. Furthermore, despite Thailand having high DTP vaccine coverage, our model predicts that there will be diphtheria outbreaks after the year 2014 due to waning immunity. Our model also suggests that providing booster doses to some susceptible individuals and those with partial immunity every 10 years is a potential way to inhibit future diphtheria outbreaks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic and prognostic value of factor VIII binding antibodies in acquired hemophilia A: data from the GTH-AH 01/2010 study.

PubMed

Werwitzke, S; Geisen, U; Nowak-Göttl, U; Eichler, H; Stephan, B; Scholz, U; Holstein, K; Klamroth, R; Knöbl, P; Huth-Kühne, A; Bomke, B; Tiede, A

2016-05-01

Essentials Factor VIII (FVIII) binding IgG detected by ELISA could be an alternative to the Bethesda assay. We studied the performance of anti-FVIII IgG ELISA in patients with acquired hemophilia and controls. Anti-FVIII IgG > 99th percentile of controls was highly sensitive and specific. Patients with high anti-FVIII IgG have a lower chance of achieving remission. Background Acquired hemophilia A is a severe bleeding disorder that requires fast and accurate diagnosis as it occurs often unexpectedly in previously healthy men and women of every age. The Nijmegen-modified Bethesda assay is the diagnostic reference standard for detecting neutralizing autoantibodies against factor VIII (FVIII), but is not widely available, not ideal for quantifying the complex type 2 inhibitors seen in acquired hemophilia, and suffers from high inter-laboratory variability. Objectives To assess the diagnostic and prognostic value of FVIII-binding antibodies as detected by ELISA compared with the Nijmegen Bethesda assay. Methods Samples from the time of first diagnosis and clinical data were available from 102 patients with acquired hemophilia enrolled in the prospective GTH-AH 01/2010 study. Controls (n = 102) were matched for gender and age. Diagnostic cut-offs were determined by receiver-operator curve analysis. The prognostic value was assessed in 92 of the 102 patients by Cox regression analysis of time to partial remission. Results Anti-FVIII IgG above the 99th percentile (> 15 arbitrary units per mL) revealed high sensitivity and specificity (both 0.99; 95% confidence interval, 0.95-1.0) for diagnosing acquired hemophilia. The likelihood of achieving partial remission was related to anti-FVIII IgG concentration (< 300 arbitrary units, 1.0; 300-1050, 0.65; > 1050, 0.39). The Bethesda titer was only associated with the likelihood of partial remission when analyzed in the central laboratory, but not when data from local GTH study sites were used. Conclusion Although the Nijmegen-modified Bethesda assay is the reference standard for demonstrating neutralizing antibodies, the detection of FVIII-binding antibodies by ELISA is similarly sensitive and specific for diagnosing acquired hemophilia. In addition, anti-FVIII IgG may provide prognostic information. © 2016 International Society on Thrombosis and Haemostasis.

Selectively active markers for solving of the partial occlusion problem in matchmoving and chromakeying workflow

NASA Astrophysics Data System (ADS)

Mazurek, Przemysław

2013-09-01

Matchmoving (Match Moving) is the process used for the estimation of camera movements for further integration of acquired video image with computer graphics. The estimation of movements is possible using pattern recognition, 2D and 3D tracking algorithms. The main problem for the workflow is the partial occlusion of markers by the actor, because manual rotoscoping is necessary for fixing of the chroma-keyed footage. In the paper, the partial occlusion problem is solved using the invented, selectively active electronic markers. The sensor network with multiple infrared links detects occlusion state (no-occlusion, partial, full) and switch LED's based markers.

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

Effects of intensive neuropsychological rehabilitation for acquired brain injury.

PubMed

Holleman, Meike; Vink, Martie; Nijland, Rinske; Schmand, Ben

2018-06-01

The objective of the study was to examine the effects of a comprehensive neuropsychological rehabilitation programme (Intensive NeuroRehabilitation, INR) on the emotional and behavioural consequences of acquired brain injury (ABI). The participants were 75 adult patients suffering from ABI (33 traumatic brain injury, 14 stroke, 10 tumour, 6 hypoxia, 12 other), all of whom were admitted to the INR treatment programme. The main outcome measures were: general psychological well-being (Symptom-Checklist-90), depression and anxiety (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, State Trait Anxiety Inventory), and quality of life (Quality of Life in Brain Injury). The study was a non-blinded, waiting-list controlled trial. During the waiting-list period no or minimal care was provided. Multivariate analysis of the main outcome measures showed large effect sizes for psychological well-being (partial η 2  = .191, p < .001), depression (partial η 2  = .168, p < .001), and anxiety (partial η 2  = .182, p < .001), and a moderate effect size for quality of life (partial η 2  = .130, p = .001). Changes on neuropsychological tests did not differ between the groups. It was concluded that the INR programme improved general psychological well-being, depressive symptoms, anxiety, and quality of life. The programme does not affect cognitive functioning.

Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells.

PubMed

Ouyang, Wen; Yang, Chunxu; Zhang, Simin; Liu, Yu; Yang, Bo; Zhang, Junhong; Zhou, Fuxiang; Zhou, Yunfeng; Xie, Conghua

2013-02-01

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a major limitation for its clinical use. The mechanisms of TRAIL resistance have been mostly studied in the context of cell lines that are intrinsically resistant to TRAIL. However, little is known about the molecular alterations that contribute to the development of acquired resistance during treatment with TRAIL. In this study, we established H460R, an isogenic cell line with acquired TRAIL resistance, from the TRAIL‑sensitive human lung cancer cell line H460 to investigate the mechanisms of acquired resistance. The acquired TRAIL‑resistant H460R cells remained sensitive to cisplatin. The mRNA and protein expression levels of death receptor 4 (DR4) and death receptor 5 (DR5) were not altered in either of the TRAIL-treated cell lines. Nevertheless, tests in which the DR4 or DR5 gene was overexpressed or silenced suggest that death receptor expression is necessary but not sufficient for TRAIL‑induced apoptosis. Compared with parental TRAIL-sensitive H460 cells, H460R cells showed a decreased TRAIL-induced translocation of DR4/DR5 into lipid rafts. Further studies showed that nystatin partially prevented lipid raft aggregation and DR4 and DR5 clustering and reduced apoptosis in H460 cells again. Analysis of apoptotic molecules showed that more pro-caspase-8, FADD, caspase-3 and Bid, but less cFLIP in H460 cells than in H460R cells. Our findings suggest that the lack of death receptor redistribution negatively impacts DISC assembly in lipid rafts, which at least partially leads to the development of acquired resistance to TRAIL in H460R cells.

Increased Small-World Network Topology Following Deployment-Acquired Traumatic Brain Injury Associated with the Development of Post-Traumatic Stress Disorder.

PubMed

Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Dobbins, Dorothy L; Rogers, Emily; Godwin, Dwayne W; Taber, Katherine H

2018-05-01

Cross-sectional and longitudinal studies in active duty and veteran cohorts have both demonstrated that deployment-acquired traumatic brain injury (TBI) is an independent risk factor for developing post-traumatic stress disorder (PTSD), beyond confounds such as combat exposure, physical injury, predeployment TBI, and pre-deployment psychiatric symptoms. This study investigated how resting-state brain networks differ between individuals who developed PTSD and those who did not following deployment-acquired TBI. Participants included postdeployment veterans with deployment-acquired TBI history both with and without current PTSD diagnosis. Graph metrics, including small-worldness, clustering coefficient, and modularity, were calculated from individually constructed whole-brain networks based on 5-min eyes-open resting-state magnetoencephalography (MEG) recordings. Analyses were adjusted for age and premorbid IQ. Results demonstrated that participants with current PTSD displayed higher levels of small-worldness, F(1,12) = 5.364, p < 0.039, partial eta squared = 0.309, and Cohen's d = 0.972, and clustering coefficient, F(1, 12) = 12.204, p < 0.004, partial eta squared = 0.504, and Cohen's d = 0.905, than participants without current PTSD. There were no between-group differences in modularity or the number of modules present. These findings are consistent with a hyperconnectivity hypothesis of the effect of TBI history on functional networks rather than a disconnection hypothesis, demonstrating increased levels of clustering coefficient rather than a decrease as might be expected; however, these results do not account for potential changes in brain structure. These results demonstrate the potential pathological sequelae of changes in functional brain networks following deployment-acquired TBI and represent potential neurobiological changes associated with deployment-acquired TBI that may increase the risk of subsequently developing PTSD.

A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus.

PubMed

Barateau, Alice; Vadrot, Nathalie; Vicart, Patrick; Ferreiro, Ana; Mayer, Michèle; Héron, Delphine; Vigouroux, Corinne; Buendia, Brigitte

2017-01-01

A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes (progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy (L-CMD) and lipodystrophy. In culture, the patient's skin fibroblasts entered prematurely into senescence, and some nuclei showed a lamina honeycomb pattern. C2C12 myoblasts were transfected with a construct carrying the patient's mutation; R388P-lamin A (LA) predominantly accumulated within the nucleoplasm and was depleted at the nuclear periphery, altering the anchorage of the inner nuclear membrane protein emerin and the nucleoplasmic protein LAP2-alpha. The mutant LA triggered a frequent and severe nuclear dysmorphy that occurred independently of prelamin A processing, as well as increased histone H3K9 acetylation. Nuclear dysmorphy was not significantly improved when transfected cells were treated with drugs disrupting microtubules or actin filaments or modifying the global histone acetylation pattern. Therefore, releasing any force exerted at the nuclear envelope by the cytoskeleton or chromatin did not rescue nuclear shape, in contrast to what was previously shown in Hutchinson-Gilford progeria due to other LMNA mutations. Our results point to the specific cytotoxic effect of the R388P-lamin A mutant, which is clinically related to a rare and severe multisystemic laminopathy phenotype.

"Surgical" abdomen in a patient with chronic lymphocytic leukemia: a case of acquired angioedema.

PubMed

Jung, Moonjung; Rice, Lawrence

2011-12-01

Acquired angioedema (AAE), an acquired deficiency of C1esterase inhibitor, is a medically treatable condition which can cause severe abdominal pain mimicking an acute surgical abdomen. This disorder is strongly associated with chronic lymphocytic leukemia (CLL) and other indolent lymphoplasmacytic disorders. We describe a patient with known CLL who developed incapacitating, recurrent severe abdominal pains, culminating in partial bowel resection. Signs, symptoms, laboratory and pathologic findings demonstrated AAE. Wider appreciation of the possibility of AAE, particularly in patients with lymphoproliferative disorders, could lead to preventive therapy and spare unnecessary surgery. This is more important now that more effective medical therapies are available.

A prospective study to evaluate a residential community reintegration program for patients with chronic acquired brain injury.

PubMed

Geurtsen, Gert J; van Heugten, Caroline M; Martina, Juan D; Rietveld, Antonius C; Meijer, Ron; Geurts, Alexander C

2011-05-01

To examine the effects of a residential community reintegration program on independent living, societal participation, emotional well-being, and quality of life in patients with chronic acquired brain injury and psychosocial problems hampering societal participation. A prospective cohort study with a 3-month waiting list control period and 1-year follow up. A tertiary rehabilitation center for acquired brain injury. Patients (N=70) with acquired brain injury (46 men; mean age, 25.1y; mean time post-onset, 5.2y; at follow up n=67). A structured residential treatment program was offered directed at improving independence in domestic life, work, leisure time, and social interactions. Community Integration Questionnaire (CIQ), Employability Rating Scale, living situation, school, work situation, work hours, Center for Epidemiological Studies Depression Scale, EuroQOL quality of life scale (2 scales), World Health Organization Quality of Life Scale Abbreviated (WHOQOL-BREF; 5 scales), and the Global Assessment of Functioning (GAF) scale. There was an overall significant time effect for all outcome measures (multiple analysis of variance T(2)=26.16; F(36,557) 134.9; P=.000). There was no spontaneous recovery during the waiting-list period. The effect sizes for the CIQ, Employability Rating Scale, work hours, and GAF were large (partial η(2)=0.25, 0.35, 0.22, and 0.72, respectively). The effect sizes were moderate for 7 of the 8 emotional well-being and quality of life (sub)scales (partial η(2)=0.11-0.20). The WHOQOL-BREF environment subscale showed a small effect size (partial η(2)=0.05). Living independently rose from 25.4% before treatment to 72.4% after treatment and was still 65.7% at follow up. This study shows that a residential community reintegration program leads to significant and relevant improvements of independent living, societal participation, emotional well-being, and quality of life in patients with chronic acquired brain injury and psychosocial problems hampering societal participation. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Quantification of Liver Fat with Magnetic Resonance Imaging

PubMed Central

Reeder, Scott B.; Sirlin, Claude

2010-01-01

Intracellular fat accumulation is common feature of liver disease. Intracellular fat (steatosis) is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

Leptin and Hormones: Energy Homeostasis.

PubMed

Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

2016-09-01

Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

PubMed Central

Park, Hyeong-Kyu; Ahima, Rexford S.

2014-01-01

Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

Crystallographic data processing for free-electron laser sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Thomas A., E-mail: taw@physics.org; Barty, Anton; Stellato, Francesco

2013-07-01

A processing pipeline for diffraction data acquired using the ‘serial crystallography’ methodology with a free-electron laser source is described with reference to the crystallographic analysis suite CrystFEL and the pre-processing program Cheetah. A processing pipeline for diffraction data acquired using the ‘serial crystallography’ methodology with a free-electron laser source is described with reference to the crystallographic analysis suite CrystFEL and the pre-processing program Cheetah. A detailed analysis of the nature and impact of indexing ambiguities is presented. Simulations of the Monte Carlo integration scheme, which accounts for the partially recorded nature of the diffraction intensities, are presented and show thatmore » the integration of partial reflections could be made to converge more quickly if the bandwidth of the X-rays were to be increased by a small amount or if a slight convergence angle were introduced into the incident beam.« less

Automatic segmentation of MR brain images of preterm infants using supervised classification.

PubMed

Moeskops, Pim; Benders, Manon J N L; Chiţ, Sabina M; Kersbergen, Karina J; Groenendaal, Floris; de Vries, Linda S; Viergever, Max A; Išgum, Ivana

2015-09-01

Preterm birth is often associated with impaired brain development. The state and expected progression of preterm brain development can be evaluated using quantitative assessment of MR images. Such measurements require accurate segmentation of different tissue types in those images. This paper presents an algorithm for the automatic segmentation of unmyelinated white matter (WM), cortical grey matter (GM), and cerebrospinal fluid in the extracerebral space (CSF). The algorithm uses supervised voxel classification in three subsequent stages. In the first stage, voxels that can easily be assigned to one of the three tissue types are labelled. In the second stage, dedicated analysis of the remaining voxels is performed. The first and the second stages both use two-class classification for each tissue type separately. Possible inconsistencies that could result from these tissue-specific segmentation stages are resolved in the third stage, which performs multi-class classification. A set of T1- and T2-weighted images was analysed, but the optimised system performs automatic segmentation using a T2-weighted image only. We have investigated the performance of the algorithm when using training data randomly selected from completely annotated images as well as when using training data from only partially annotated images. The method was evaluated on images of preterm infants acquired at 30 and 40weeks postmenstrual age (PMA). When the method was trained using random selection from the completely annotated images, the average Dice coefficients were 0.95 for WM, 0.81 for GM, and 0.89 for CSF on an independent set of images acquired at 30weeks PMA. When the method was trained using only the partially annotated images, the average Dice coefficients were 0.95 for WM, 0.78 for GM and 0.87 for CSF for the images acquired at 30weeks PMA, and 0.92 for WM, 0.80 for GM and 0.85 for CSF for the images acquired at 40weeks PMA. Even though the segmentations obtained using training data from the partially annotated images resulted in slightly lower Dice coefficients, the performance in all experiments was close to that of a second human expert (0.93 for WM, 0.79 for GM and 0.86 for CSF for the images acquired at 30weeks, and 0.94 for WM, 0.76 for GM and 0.87 for CSF for the images acquired at 40weeks). These results show that the presented method is robust to age and acquisition protocol and that it performs accurate segmentation of WM, GM, and CSF when the training data is extracted from complete annotations as well as when the training data is extracted from partial annotations only. This extends the applicability of the method by reducing the time and effort necessary to create training data in a population with different characteristics. Copyright © 2015 Elsevier Inc. All rights reserved.

Hepatic fibrosis and factors associated with liver stiffness in HIV mono-infected individuals

PubMed Central

Ferenci, Tamás; Makara, Mihály; Horváth, Gábor; Szlávik, János; Rupnik, Zsófia; Kormos, Luca; Gerlei, Zsuzsanna; Sulyok, Zita; Vályi-Nagy, István

2017-01-01

Background Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake. Methods We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness. Results Liver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated. Discussion Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations. PMID:28097068

Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients.

PubMed

Ravelli, Angelo; Trail, Lucia; Ferrari, Cristina; Ruperto, Nicolino; Pistorio, Angela; Pilkington, Clarissa; Maillard, Susan; Oliveira, Sheila K; Sztajnbok, Flavio; Cuttica, Ruben; Beltramelli, Matilde; Corona, Fabrizia; Katsicas, Maria Martha; Russo, Ricardo; Ferriani, Virginia; Burgos-Vargas, Ruben; Magni-Manzoni, Silvia; Solis-Valleoj, Eunice; Bandeira, Marcia; Zulian, Francesco; Baca, Vicente; Cortis, Elisabetta; Falcini, Fernanda; Alessio, Maria; Alpigiani, Maria Giannina; Gerloni, Valeria; Saad-Magalhaes, Claudia; Podda, Rosanna; Silva, Clovis A; Lepore, Loredana; Felici, Enrico; Rossi, Federica; Sala, Elena; Martini, Alberto

2010-01-15

To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL). A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Hypertriglyceridemia and Waist Circumference Predict Cardiovascular Risk among HIV Patients: A Cross-Sectional Study

PubMed Central

Janiszewski, Peter M.; Ross, Robert; Despres, Jean-Pierre; Lemieux, Isabelle; Orlando, Gabriella; Carli, Federica; Bagni, Pietro; Menozzi, Marianna; Zona, Stefano; Guaraldi, Giovanni

2011-01-01

Background Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women. Methods 1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast. Results The high TG/high WC men had the most VAT (208.0±94.4 cm2), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3±6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0±97.9 cm2) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9±2.8) by comparison to low TG/low WC women (p<0.05 for all). Conclusions A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients. PMID:21966404

HIV or HIV-Therapy? Causal attributions of symptoms and their impact on treatment decisions among women and men with HIV

PubMed Central

2009-01-01

Objectives Among people with HIV, we examined symptom attribution to HIV or HIV-therapy, awareness of potential side effects and discontinuation of treatment, as well as sex/gender differences. Methods HIV-patients (N = 168, 46% female) completed a comprehensive symptom checklist (attributing each endorsed symptom to HIV, HIV-therapy, or other causes), reported reasons for treatment discontinuations and potential ART-related laboratory abnormalities. Results Main symptom areas were fatigue/sleep/energy, depression/mood, lipodystrophy, and gastrointestinal, dermatological, and neurological problems. Top HIV-attributed symptoms were lack of stamina/energy in both genders, night sweats, depression, mood swings in women; and fatigue, lethargy, difficulties concentrating in men. Women attributed symptoms less frequently to HIV than men, particularly fa-tigue(p < .01). Top treatment-attributed symptoms were lipodystrophy and gastrointestinal problems in both genders. Symptom attribution to HIV-therapy did not differ between genders. Over the past six months, 22% switched/interrupted ART due to side effects. In women, side effect-related treatment decisions were more complex, involving more side effects and substances. Remarkably, women took predominantly protease inhibitor-sparing regimens (p = .05). Both genders reported only 15% of potential ART-related laboratory abnormalities but more than 50% had laboratory abnormalities. Notably, women had fewer elevated renal parameters (p < .01). Conclusions Men may attribute symptoms more often to HIV and maintain a treatment-regimen despite side effects, whereas women may be more prudent in avoiding treatment side effects. Lacking awareness of laboratory abnormalities in both genders potentially indicates gaps in physician-patient communication. Gender differences in causal attributions of symptoms/side effects may influence treatment decisions. PMID:19380286

Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome.

PubMed

Lungu, Andreea O; Zadeh, Elika Safar; Goodling, Anne; Cochran, Elaine; Gorden, Phillip

2012-02-01

The lipodystrophies (LD) are characterized by metabolic abnormalities (insulin resistance, hypertriglyceridemia, and diabetes) and a polycystic ovarian syndrome (PCOS) phenotype. Therapeutic administration of leptin improves insulin sensitivity and the metabolic features. The objective of the study was to investigate whether the PCOS features are corrected by increasing insulin sensitivity as a function of leptin treatment. This was a prospective, open-label trial using leptin replacement in various forms of lipodystrophy. The study was performed at the Clinical Center at the National Institutes of Health. Twenty-three female patients with LD were enrolled in a leptin replacement trial from 2000 to the present. Different parameters were assessed at baseline and after 1 yr of therapy. Patients were treated with leptin for at least 1 yr. We evaluated free testosterone, SHBG, and IGF-I at baseline and after 1 yr of leptin. Testosterone levels decreased from 3.05 ±0.6 ng/ml at baseline to 1.7 ±0.3 ng/ml (P = 0.02). SHBG increased from 14.5 ±2 to 25 ±3.5 nmol/liter after 1 yr of leptin therapy. There were no significant changes in the levels of gonadotropins and ovarian size as a result of leptin replacement therapy. IGF-I increased significantly after leptin therapy from 150 ±14 to 195 ±17. There was a significant decrease in triglycerides and glycosylated hemoglobin in the context of reduced insulin requirements. In the present study, we show that LD may be a model for the common forms of PCOS and that the endocrine features are corrected by leptin therapy, which reduces insulin resistance.

Type 1 diabetes: Syndromes in resource-challenged settings.

PubMed

Nagesh, V Sri; Kalra, Sanjay

2015-06-01

Type 1 Diabetes is a complex disorder that is made more complex by the myriad of co-morbid conditions associated with it. Mauriac Syndrome is a well-known but nowadays uncommon condition that presents with growth retardation secondary to poor glycaemic control. Limited Joint Mobility is an often-missed association of diabetes. Its importance lies in the fact that it can cause significant impairment of fine movements in T1DM children. It also indicates poor glycaemic control over a long period of time and can be used as a surrogate marker for development of diabetic microvascular complications. Anaemia in T1DM is protean and can develop due to a combination of nutritional factors, chronic renal disease, coeliac disease and worm infestation. Management is etiological. Vitamin deficiencies are ubiquitous in T1DM and if left untreated, can lead to neurological, haematological and skeletal dysfunction. The best-known co-morbid conditions are the local site reactions clubbed together under the moniker lipodystrophies. These can be either atrophic or hypertrophic and are usually due to repeated injections at the same site, improper technique and needle re-use. Management is often difficult and they are best prevented by appropriate diabetes education and emphasis on proper injection techniques at the time of T1DM diagnosis, with periodic reinforcement. Amyloidosis is a little known condition that shares a lot of features in common with the lipodystrophies and often needs to be differentiated from lipohypertrophy. T1DM is a disease which is often associated with a poor quality of life and these co-morbid conditions also need to be treated for effective general and psychological well-being.

Correlation between Lumbar Lordosis Angle and Degree of Gynoid Lipodystrophy (Cellulite) in Asymptomatic Women

PubMed Central

Milani, Giovana Barbosa; Filho, A’Dayr Natal; João, Sílvia Maria Amado

2008-01-01

INTRODUCTION Gynoid lipodystrophy (cellulite) has been cited as a common dermatological alteration. It occurs mainly in adult women and tends to gather around the thighs and buttocks. Its presence and severity have been related to many factors, including biotype, age, sex, circulatory changes, and, as some authors have suggested, mechanical alterations such as lumbar hyperlordosis. OBJECTIVE To correlate the degree of cellulite with the angle of lumbar lordosis in asymptomatic women. METHODS Fifty volunteers were evaluated by digital photos, palpation, and thermograph. The degree of cellulite was classified on a scale of 1–4. Analyses were performed on the superior, inferior, right and left buttocks (SRB, IRB, SLB, ILB), and the superior right and left thighs (SRT, SLT). The volunteers underwent a lateral-view X-ray, and the angle of lumbar lordosis was measured using Cobb’s method (inferior endplate of T12 and the superior endplate of S). The data were statistically analyzed using ANOVA and Spearman’s correlation. A significance level of 5% was adopted. RESULTS Volunteers had a mean age of 26.1 ± 4.4 years and a mean body mass index of 20.7 ± 1.9 kg/m2. There was no significant difference in lumbar lordosis angle between those with cellulite classes 2 and 3 (p ≥ 0.297). There was also no correlation between lumbar lordosis angle and the degree of cellulite (p ≥ 0.085 and r ≥ 0.246). CONCLUSIONS The analysis suggests that there is no correlation between the degree of cellulite and the angle of lumbar lordosis as measured using Cobb’s method. PMID:18719762

The Effects of Diet Composition on Body Fat and Hepatic Steatosis in an Animal (Peromyscus californicus) Model of the Metabolic Syndrome

PubMed Central

Krugner-Higby, Lisa; Caldwell, Stephen; Coyle, Kathryn; Bush, Eugene; Atkinson, Richard; Joers, Valerie

2011-01-01

The objective of this research was to determine body composition, total fat content, fat distribution, and serum leptin concentration in hyperlipidemic (high responder, HR) and normolipidemic (low responder, LR) California mice (Peromyscus californicus). In our initial experiments, we sought to determine whether differences in regional fat storage were associated with hyperlipidemia in this species. To further characterize the hepatic steatosis in the mice, we performed 2 additional experiments by using a diet containing 45% of energy as fat. The body fat content of mice fed a low fat-diet (12.3% energy as fat) was higher than that of mice fed a moderate-fat diet (25.8% energy as fat). Total body fat did not differ between HR and LR mice. There was no significant difference between intraabdominal, gonadal, or inguinal fat pad weights. Liver weights of HR mice fed the moderate-fat diet were higher than those of LR mice fed the same diet, and the moderate-fat diet was associated with nonalcoholic fatty liver (NAFL). Mice fed the 45% diet had higher histologic score for steatosis but very little inflammatory response. Chemical analysis indicated increased lipid in the livers of mice fed the high-fat diet compared with those fed the low-fat diet. HR and LR mice had similar serum leptin concentrations. California mice develop NAFL without excess fat accumulation elsewhere. NAFL was influenced by genetic and dietary factors. These mice may be a naturally occuring model of partial lipodystrophy. PMID:21819679

Selection of molecular descriptors with artificial intelligence for the understanding of HIV-1 protease peptidomimetic inhibitors-activity.

PubMed

Sirois, S; Tsoukas, C M; Chou, Kuo-Chen; Wei, Dongqing; Boucher, C; Hatzakis, G E

2005-03-01

Quantitative Structure Activity Relationship (QSAR) techniques are used routinely by computational chemists in drug discovery and development to analyze datasets of compounds. Quantitative numerical methods like Partial Least Squares (PLS) and Artificial Neural Networks (ANN) have been used on QSAR to establish correlations between molecular properties and bioactivity. However, ANN may be advantageous over PLS because it considers the interrelations of the modeled variables. This study focused on the HIV-1 Protease (HIV-1 Pr) inhibitors belonging to the peptidomimetic class of compounds. The main objective was to select molecular descriptors with the best predictive value for antiviral potency (Ki). PLS and ANN were used to predict Ki activity of HIV-1 Pr inhibitors and the results were compared. To address the issue of dimensionality reduction, Genetic Algorithms (GA) were used for variable selection and their performance was compared against that of ANN. Finally, the structure of the optimum ANN achieving the highest Pearson's-R coefficient was determined. On the basis of Pearson's-R, PLS and ANN were compared to determine which exhibits maximum performance. Training and validation of models was performed on 15 random split sets of the master dataset consisted of 231 compounds. For each compound 192 molecular descriptors were considered. The molecular structure and constant of inhibition (Ki) were selected from the NIAID database. Study findings suggested that non-covalent interactions such as hydrophobicity, shape and hydrogen bonding describe well the antiviral activity of the HIV-1 Pr compounds. The significance of lipophilicity and relationship to HIV-1 associated hyperlipidemia and lipodystrophy syndrome warrant further investigation.

Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects.

PubMed

Owen, Katharine R; Groves, Christopher J; Hanson, Robert L; Knowler, William C; Shuldiner, Alan R; Elbein, Steven C; Mitchell, Braxton D; Froguel, Philippe; Ng, Maggie C Y; Chan, Juliana C; Jia, Weiping; Deloukas, Panos; Hitman, Graham A; Walker, Mark; Frayling, Timothy M; Hattersley, Andrew T; Zeggini, Eleftheria; McCarthy, Mark I

2007-03-01

Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial lipodystrophy, a syndrome of monogenic insulin resistance and diabetes. LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components. We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs capturing >90% of common variation) in several large datasets. Analysis of 2,490 U.K. diabetic case and 2,556 control subjects revealed no significant associations at either genotype or haplotype level: the minor allele at rs4641 was no more frequent in case subjects (allelic odds ratio [OR] 1.07 [95% CI 0.98-1.17], P = 0.15). In 390 U.K. trios, family-based association analyses revealed nominally significant overtransmission of the major allele at rs12063564 (P = 0.01), which was not corroborated in other samples. Finally, genotypes for 2,817 additional subjects from the International 1q Consortium revealed no consistent case-control or family-based associations with LMNA variants. Across all our data, the OR for the rs4641 minor allele approached but did not attain significance (1.07 [0.99-1.15], P = 0.08). Our data do not therefore support a major effect of LMNA variation on diabetes risk. However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001).

48 CFR 45.000 - Scope of part.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Government has acquired a lien or title solely because of partial, advance, progress, or performance-based... Section 45.000 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT... Government property to contractors, contractors' management and use of Government property, and reporting...

Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

PubMed Central

Kalra, Satya P.

2013-01-01

Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable glycemia for lifetime. PMID:24251168

Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

PubMed

Kalra, Satya P

2013-10-01

Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable glycemia for lifetime.

Laser, light, and energy devices for cellulite and lipodystrophy.

PubMed

Peterson, Jennifer D; Goldman, Mitchel P

2011-07-01

Cellulite affects all races, and it is estimated that 85% of women older than 20 years have some degree of cellulite. Many currently accepted cellulite therapies target deficiencies in lymphatic drainage and microvascular circulation. Devices using radiofrequency, laser, and light-based energies, alone or in combination and coupled frequently with tissue manipulation, are available for improving cellulite. Laser assisted liposuction may improve cellulite appearance. Although improvement using these devices is temporary, it may last several months. Patients who want smoother skin with less visible cellulite can undergo a series of treatments and then return for additional treatments as necessary. Copyright © 2011 Elsevier Inc. All rights reserved.

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism.

PubMed

Park, Hyeong-Kyu; Ahima, Rexford S

2015-01-01

Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

From wasting to obesity, changes in nutritional concerns in HIV/AIDS.

PubMed

Mankal, Pavan K; Kotler, Donald P

2014-09-01

Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Acquired antiprothrombin antibodies: an unusual cause of bleeding.

PubMed

Carvalho, Cristiana; Viveiro, Carolina; Maia, Paulo; Rezende, Teresa

2013-01-07

Acquired inhibitors of coagulation causing bleeding manifestations are rare in children. They emerge, normally in the context of autoimmune diseases or drug ingestion, but transient and self-limiting cases can occur after viral infection. We describe, an otherwise healthy, 7-year-old girl who had gingival bleeding after a tooth extraction. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were both prolonged with evidence of an immediate acting inhibitor (lupic anticoagulant). Further coagulation studies demonstrated prothrombin (FII) deficiency and prothrombin directed (FII) antibodies. The serological tests to detect an underlying autoimmune disease were all negative. The coagulation studies normalised alongside the disappearance of the antibody. This article presents lupus anticoagulant hypoprothrombinaemia syndrome (LAHS) as a rare case of acquired bleeding diathesis in childhood.

Highly accelerated cardiac cine parallel MRI using low-rank matrix completion and partial separability model

NASA Astrophysics Data System (ADS)

Lyu, Jingyuan; Nakarmi, Ukash; Zhang, Chaoyi; Ying, Leslie

2016-05-01

This paper presents a new approach to highly accelerated dynamic parallel MRI using low rank matrix completion, partial separability (PS) model. In data acquisition, k-space data is moderately randomly undersampled at the center kspace navigator locations, but highly undersampled at the outer k-space for each temporal frame. In reconstruction, the navigator data is reconstructed from undersampled data using structured low-rank matrix completion. After all the unacquired navigator data is estimated, the partial separable model is used to obtain partial k-t data. Then the parallel imaging method is used to acquire the entire dynamic image series from highly undersampled data. The proposed method has shown to achieve high quality reconstructions with reduction factors up to 31, and temporal resolution of 29ms, when the conventional PS method fails.

Transient Reactive Eruptive Lymphangiectasia Following Partial Vulvectomy for Chronic Acquired Lymphangioma.

PubMed

Wirth, Paul J; Lin, Lin

2017-01-01

A 64-year-old white woman was originally diagnosed with histiocytic lymphoma in 1977. She had bilateral lymph node biopsies of the groin, chemotherapy, and radiation therapy after her diagnosis had been confirmed pathologically. She was treated with prednisone and vincristine.

AIDS Knowledge: The Media and the Biology Teacher.

ERIC Educational Resources Information Center

Vener, Arthur M.; Krupka, Lawrence R.

1988-01-01

Reports on a study to determine the level of knowledge college students possessed about Acquired Immune Deficiency Syndrome. Concluded that overall enhancement of knowledge occurred among young adults and that mass media was partially responsible. Lists biological terms necessary for understanding the disease. (RT)

Reliability of the Client-Centeredness of Goal Setting (C-COGS) Scale in Acquired Brain Injury Rehabilitation.

PubMed

Doig, Emmah; Prescott, Sarah; Fleming, Jennifer; Cornwell, Petrea; Kuipers, Pim

2016-01-01

To examine the internal reliability and test-retest reliability of the Client-Centeredness of Goal Setting (C-COGS) scale. The C-COGS scale was administered to 42 participants with acquired brain injury after completion of multidisciplinary goal planning. Internal reliability of scale items was examined using item-partial total correlations and Cronbach's α coefficient. The scale was readministered within a 1-mo period to a subsample of 12 participants to examine test-retest reliability by calculating exact and close percentage agreement for each item. After examination of item-partial total correlations, test items were revised. The revised items demonstrated stronger internal consistency than the original items. Preliminary evaluation of test-retest reliability was fair, with an average exact percent agreement across all test items of 67%. Findings support the preliminary reliability of the C-COGS scale as a tool to evaluate and promote client-centered goal planning in brain injury rehabilitation. Copyright © 2016 by the American Occupational Therapy Association, Inc.

High frequency of empty sella syndrome in children with growth hormone deficiency.

PubMed

Pocecco, M; de Campo, C; Marinoni, S; Tommasini, G; Basso, T; Muzzolini, C; Sacher, B

1989-02-01

Computer-assisted tomography (CT) with 2 mm axial sections and reconstructions was carried out in 31 children affected by GH deficiency (GHD): 18 with idiopathic complete isolated GHD, 3 with idiopathic partial isolated GHD, 2 with idiopathic panhypopituitarism, 4 with isolated acquired GHD and 4 with acquired panhypopituitarism. Density in the intrasellar area on CT corresponded to that of cerebrospinal fluid in 13/20 cases with idiopathic hypopituitarism and in 2/8 cases with acquired hypopituitarism. The overall incidence of primary empty sella syndrome (PESS) in the GH deficient patients studied was thus over 48%, while in children without endocrine dysfunction, it was only 5/213 (2.4%). It is concluded that PESS is more frequent in childhood than assumed until now and that it is frequently associated with GHD.

The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks.

PubMed

Briand, Nolwenn; Guénantin, Anne-Claire; Jeziorowska, Dorota; Shah, Akshay; Mantecon, Matthieu; Capel, Emilie; Garcia, Marie; Oldenburg, Anja; Paulsen, Jonas; Hulot, Jean-Sebastien; Vigouroux, Corinne; Collas, Philippe

2018-04-15

The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigan-type (FPLD2), a lipodystrophic syndrome complicated by early onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2. Genome modeling in fibroblasts from patients with FPLD2 caused by the lamin A R482W mutation reveals repositioning of the mesodermal regulator T/Brachyury locus towards the nuclear center relative to normal fibroblasts, suggesting enhanced activation propensity of the locus in a developmental model of FPLD2. Addressing this issue, we report phenotypic and transcriptional alterations in mesodermal and endothelial differentiation of induced pluripotent stem cells we generated from a patient with R482W-associated FPLD2. Correction of the LMNA mutation ameliorates R482W-associated phenotypes and gene expression. Transcriptomics links endothelial differentiation defects to decreased Polycomb-mediated repression of the T/Brachyury locus and over-activation of T target genes. Binding of the Polycomb repressor complex 2 to T/Brachyury is impaired by the mutated lamin A network, which is unable to properly associate with the locus. This leads to a deregulation of vascular gene expression over time. By connecting a lipodystrophic hotspot lamin A mutation to a disruption of early mesodermal gene expression and defective endothelial differentiation, we propose that the mutation rewires the fate of several lineages, resulting in multi-tissue pathogenic phenotypes.

Browsing at 'Bylot'

NASA Technical Reports Server (NTRS)

2004-01-01

This mosaic, featuring the rock target dubbed 'Bylot,' was acquired by NASA's Mars Exploration Rover Opportunity on sol 194 (Aug. 9, 2004). It consists of four images taken by the rover's microscopic imager. The spherules shown here are less round than the 'blueberries' seen previously in 'Endurance Crater,' perhaps because the minerals coating them are more resistant to erosion. Dark sand is partially covering the rock. The target was in complete shadow when the images were acquired, except for a small area at the upper right, where direct sunlight caused the camera to saturate and excess charge to 'bloom' downward into adjacent pixels.

An outline of main factors of drug resistance influencing cancer therapy.

PubMed

Frączek, Natalia; Bronisz, Iwona; Pietryka, Magdalena; Kępińska, Dorota; Strzała, Patrycja; Mielnicka, Kamila; Korga, Agnieszka; Dudka, Jaroslaw

2016-12-01

Drug resistance in cancer therapy is a multifactorial phenomenon that determines remission or progression. It is known that resistance to used anticancer drugs may be the consequence of drug transport to the cell or intracellular distribution. It may also be the result of its molecular target structural change, apoptosis inhibition or increase in some enzymes activity, e.g. pentose phosphate pathway enzymes. Intrinsic (pre-existed) drug resistance is related to the phenotype of cancer as well as normal cells. Acquired, after partial administration of chemotherapy, type of drug resistance in addition to the starting phenotype is closely linked to the development of new more aggressive clones and adaptive processes. In both, the intrinsic and acquired resistance, role play also mutations. These may be partially spontaneous, but in terms of acquired resistance, they are mostly induced by the exposure to the drugs. The article mentions some traditional mechanisms related to the acquisition of resistance by cancer cells during therapy, through the protein transporters, apoptosis deregulation, angiogenesis and the impact of the tumour microenvironment. We focused however on some more alternative ways of therapy resistance, such as, hypoxia and tumour acidification, cancer stem cells (CSCs), exosomes and radiotherapy resistance. A concise summary of the drug resistance presented in the paper may be an important aspect in studies to increase the effectiveness of cancer therapies.

Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import.

PubMed

Götz, Veronika; Magar, Linda; Dornfeld, Dominik; Giese, Sebastian; Pohlmann, Anne; Höper, Dirk; Kong, Byung-Whi; Jans, David A; Beer, Martin; Haller, Otto; Schwemmle, Martin

2016-03-18

To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees of attenuation in mammalian and avian cells. Additionally, most of the mutant viruses lost the capacity to escape MxA restriction, with the exception of the G16D virus. We show that MxA escape is linked to attenuation by demonstrating that the three substitutions promoting MxA escape disturbed intracellular trafficking of incoming viral ribonucleoprotein complexes (vRNPs), thereby resulting in impaired nuclear import, and that the additional acquired mutations only partially compensate for this import block. We conclude that for adaptation to the human host, AIV must not only overcome MxA restriction but also an associated block in nuclear vRNP import. This inherent difficulty may partially explain the frequent failure of AIV to become pandemic.

Persistent hyperphagia in acquired brain injury; an observational case study of patients receiving inpatient rehabilitation.

PubMed

Rowell, Arleen M; Faruqui, Rafey A

2010-01-01

Morbid hunger or persistent hyperphagia is a relatively rare but potentially life threatening complication of acquired brain injury (ABI). This paper presents findings from an observational case study of patients with hyperphagia receiving inpatient neurobehavioural rehabilitation following their acquired brain injury. The case study has utilized dietetic and medical records of identified patients to confirm the persistent and serious nature of this presentation in order to extract important management principles. The findings confirmed that hyperphagia or morbid hunger posed potentially life-threatening health risks to the patient, primarily around weight control and fluid balance, and risks of aggression towards professional and family carers. Pharmacological or behaviour modification interventions were only partially successful in management of this presentation. The study identified a high need for environmental and cue exposure control in management of this condition.

The long road to leptin.

PubMed

Friedman, Jeffrey

2016-12-01

Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients. Leptin acts on neurons in the hypothalamus and elsewhere to elicit its effects, and mutations that affect the function of this neural circuit cause Mendelian forms of obesity. Leptin levels fall during starvation and elicit adaptive responses in many other physiologic systems, the net effect of which is to reduce energy expenditure. These effects include cessation of menstruation, insulin resistance, alterations of immune function, and neuroendocrine dysfunction, among others. Some or all of these effects are also seen in patients with constitutively low leptin levels, such as occur in lipodystrophy. Leptin is an approved treatment for generalized lipodystrophy, a condition associated with severe metabolic disease, and has also shown potential for the treatment of other types of diabetes. In addition, leptin restores reproductive capacity and increases bone mineral density in patients with hypothalamic amenorrhea, an infertility syndrome in females. Most obese patients have high endogenous levels of leptin, in some instances as a result of mutations in the neural circuit on which leptin acts, though in most cases, the pathogenesis of leptin resistance is not known. Obese patients with leptin resistance show a variable response to exogenous leptin but may respond to a combination of leptin plus amylin. Overall, the identification of leptin has provided a framework for studying the pathogenesis of obesity in the general population, clarified the nature of the biologic response to starvation, and helped to advance our understanding of the neural mechanisms that control feeding.

The frequency of low muscle mass and its overlap with low bone mineral density and lipodystrophy in individuals with HIV--a pilot study using DXA total body composition analysis.

PubMed

Buehring, Bjoern; Kirchner, Elizabeth; Sun, Zhiyuan; Calabrese, Leonard

2012-01-01

As a result of the advances in antiretroviral therapy, the life span of human immunodeficiency virus (HIV)-infected patients has increased dramatically. Attendant to these effects are signs of premature aging with notable changes in the musculoskeletal system. Although changes in bone and fat distribution have been studied extensively, far less is known about changes in muscle. This study examined the extent of low muscle mass (LMM) and its relationship with low bone mineral density (BMD) and lipodystrophy (LD) in HIV-positive males. As such, HIV-positive males on therapy or treatment naive underwent dual-energy X-ray absorptiometry total body composition measurements. Appendicular lean mass/(height)2 and lowest 20% of residuals from regression analysis were used to define LMM. BMD criteria defined osteopenia/osteoporosis, and the percent central fat/percent lower extremity ratio defined LD. Several potential risk factors were assessed through chart review. Sixty-six males (57 with treatment and 9 treatment naive) volunteered. Treated individuals were older than naive (44 vs 34 yr) and had HIV longer (108 vs 14 mo). When definitions for sarcopenia (SP) in elderly individuals were applied, the prevalence of LMM was 21.9% and 18.8% depending on the definition used. Low BMD was present in 68.2% of participants. LD with a cutoff of 1.5 and 1.961 was present in 54.7% and 42.2% of participants, respectively. LMM and LD were negatively associated. In conclusion, this study shows that LMM is common in males with HIV and that SP affecting muscle function could be present in a substantial number of individuals. Future research needs to examine what impact decreased muscle mass and function has on morbidity, physical function, and quality of life in individuals with HIV. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Rehabilitation of a patient with complete mandibulectomy and partial glossectomy.

PubMed

Meyerson, M D; Johnson, B H; Weitzman, R S

1980-05-01

Following a number of radiologic and surgical procedures for the treatment of oral cancer, a patient with severe facial disfigurement and alteration of the vocal tract acquired acceptable speech. Consultation among referring physicians and speech pathologists can aid such a patient by facilitating the rehabilitative process through improvement of communicative skills.

26 CFR 1.1502-21T - Net operating losses (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Net operating losses (temporary). 1.1502-21T...) INCOME TAX (CONTINUED) INCOME TAXES Computation of Consolidated Items § 1.1502-21T Net operating losses...)(B). (C) Partial waiver of carryback period for 2001 and 2002 losses—(1) Application. The acquiring...

Measurement of moisture, soluble solids, and sucrose content and mechanical properties in sugar beet using portable visible and near-infrared spectroscopy

USDA-ARS?s Scientific Manuscript database

Visible and near-infrared spectroscopy, coupled with partial least squares regression, was used to predict the moisture, soluble solids and sucrose content and mechanical properties of sugar beet. Interactance spectra were acquired from both intact and sliced beets, using two portable spectrometers ...

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

PubMed Central

Gonzaga, Vivian Fonseca; Lisboa, Gustavo Sabino; Frare, Eduardo Osório

2017-01-01

Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA. PMID:29333168

Auto-Detection of Partial Discharges in Power Cables by Descrete Wavelet Transform

NASA Astrophysics Data System (ADS)

Yasuda, Yoh; Hara, Takehisa; Urano, Koji; Chen, Min

One of the serious problems that may happen in power XLPE cables is destruction of insulator. The best and conventional way to prevent such a crucial accident is generally supposed to ascertain partial corona discharges occurring at small void in organic insulator. However, there are some difficulties to detect those partial discharges because of existence of external noises in detected data, whose patterns are hardly identified at a glance. By the reason of the problem, there have been a number of researches on the way of development to accomplish detecting partial discharges by employing neural network (NN) system, which is widely known as the system for pattern recognition. We have been developing the NN system of the auto-detection for partial discharges, which we actually input numerical data of waveform itself into and obtained appropriate performance from. In this paper, we employed Descrete Wavelet Transform (DWT) to acquire more detailed transformed data in order to put them into the NN system. Employing DWT, we became able to express the waveform data in time-frequency space, and achieved effective detectiton of partial discharges by NN system. We present here the results using DWT analysis for partial discharges and noise signals which we obtained actually. Moreover, we present results out of the NN system which were dealt with those transformed data.

Adipose tissue expandability and the early origins of PCOS.

PubMed

de Zegher, Francis; Lopez-Bermejo, Abel; Ibáñez, Lourdes

2009-11-01

The most prevalent phenotypes of polycystic ovary syndrome (PCOS) are characterized by insulin resistance and androgen excess. The adipose tissue (AT) expandability hypothesis explains the development of insulin resistance in obesity and in cases of AT deficit. In line with this hypothesis, we propose that hyperinsulinemic androgen excess in PCOS is often underpinned by exhaustion of the capacity to expand subcutaneous AT in a metabolically safe way. Such exhaustion might occur when a positive energy imbalance meets a normal fat-storage capacity and/or when a normal energy balance faces a low fat storage capacity. This concept thus explains how PCOS phenotypes might result from obesity, prenatal growth restraint or a genetic lipodystrophy, or, experimentally, from prenatal androgen excess.

Human immunodeficiency virus endocrinopathy

PubMed Central

Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

2011-01-01

Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

Challenges to diagnosis of HIV-associated wasting.

PubMed

Kotler, Donald

2004-12-01

There is a wide variability in the clinical presentation of the protein energy malnutrition often characterized as wasting in patients infected with HIV. Moreover, the clinical presentation has evolved over time. Initially, protein energy malnutrition was characterized by profound weight loss and depletion of body cell mass (BCM). Recently, unrelated concurrent metabolic abnormalities, such as lipodystrophy, may complicate the diagnosis of HIV wasting. Although measures of BCM are relatively accurate for the diagnosis of HIV wasting, the optimal tools for assessing BCM are not necessarily available to the clinician. From the practical standpoint, HIV wasting may be a self-evident diagnosis in advanced stages, but effective interpretation of the early signs of HIV wasting requires familiarity with other complications included in the differential diagnosis.

[Antioxidant activity of hepatotropic preparations in the treatment of chronic diseases of the liver].

PubMed

Loginov, A S; Matiushin, B N; Sukhareva, G V; Tkachev, V D

1988-01-01

Hepatotropic drugs were shown to decrease blood lipid peroxidation activity (LPO) in patients with chronic diffuse liver diseases. A positive time course of LPO indices was noted in the treatment of chronic active hepatitis and liver cirrhosis of moderate activity. Comparison of antioxidant features of the drugs were suggestive of a noticeable effect of trophopar and essential in patients with chronic active hepatitis, trophopar in patients with liver lipodystrophy, and drugs of a silimarina series in patients with liver cirrhosis. Under clinical conditions the effect of the drugs on LPO processes was less noticeable than in experiments in vitro. It is assumed that the pharmacological effect of the hepatotropic drugs is associated with their antioxidant activity.

Simulation of the modulation transfer function dependent on the partial Fourier fraction in dynamic contrast enhancement magnetic resonance imaging.

PubMed

Takatsu, Yasuo; Ueyama, Tsuyoshi; Miyati, Tosiaki; Yamamura, Kenichirou

2016-12-01

The image characteristics in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) depend on the partial Fourier fraction and contrast medium concentration. These characteristics were assessed and the modulation transfer function (MTF) was calculated by computer simulation. A digital phantom was created from signal intensity data acquired at different contrast medium concentrations on a breast model. The frequency images [created by fast Fourier transform (FFT)] were divided into 512 parts and rearranged to form a new image. The inverse FFT of this image yielded the MTF. From the reference data, three linear models (low, medium, and high) and three exponential models (slow, medium, and rapid) of the signal intensity were created. Smaller partial Fourier fractions, and higher gradients in the linear models, corresponded to faster MTF decline. The MTF more gradually decreased in the exponential models than in the linear models. The MTF, which reflects the image characteristics in DCE-MRI, was more degraded as the partial Fourier fraction decreased.

Laryngeal paralysis in dogs: an update on recent knowledge.

PubMed

Kitshoff, Adriaan M; Van Goethem, Bart; Stegen, Ludo; Vandekerckhov, Peter; de Rooster, Hilde

2013-04-05

Laryngeal paralysis is the effect of an inability to abduct the arytenoid cartilages during inspiration, resulting in respiratory signs consistent with partial airway obstruction. The aetiology of the disease can be congenital (hereditary laryngeal paralysis or congenital polyneuropathy), or acquired (trauma, neoplasia, polyneuropathy, endocrinopathy). The most common form of acquired laryngeal paralysis (LP) is typically seen in old, large breed dogs and is a clinical manifestation of a generalised peripheral polyneuropathy recently referred to as geriatric onset laryngeal paralysis polyneuropathy. Diagnosing LP based on clinical signs, breed and history has a very high sensitivity (90%) and can be confirmed bylaryngeal inspection. Prognosis after surgical correction depends on the aetiology: traumatic cases have a good prognosis, whereas tumour-induced or polyneuropathy-induced LP has a guarded prognosis. Acquired idiopathic LP is a slow progressive disease, with dogs reaching median survival times of 3-5 years after surgical correction.

Malignant melanoma with preserved hairs: a snap shot could suggest the development from an acquired melanocytic nevus.

PubMed

Kiyohara, Takahiro; Kouraba, Sachio; Takahashi, Hidenori; Kawasaki, Takeo; Takeuchi, Akiteru; Kumakiri, Masanobu

2010-02-01

63-year-old man presented with a dome-shaped, black nodule on his right forehead, where hairs were preserved. The black surface tone measured 7 mm in diameter and spread irregularly from the periphery of the nodule. He had been conscious of the preceding, black macule for approximately 50 years. A snap shot of the patient in adolescence showed a tiny, black macule, which was a few millimeters in diameter. Histological examination demonstrated irregular proliferation of melanoma cells from the epidermis to the dermis. Partially, there were well-circumscribed, oval nests composed of nevus cells in the acanthotic epidermis and follicles. Nevus cells were also seen in the dermal component, presenting a burnt-out appearance. In this case, the small final size, the preserved hairs and the snap shot suggested a preceding, acquired melanocytic nevus. Malignant melanoma could arise from acquired melanocytic nevus.

Mitigation of near-band balanced steady-state free precession through-plane flow artifacts using partial dephasing.

PubMed

Datta, Anjali; Cheng, Joseph Y; Hargreaves, Brian A; Baron, Corey A; Nishimura, Dwight G

2018-06-01

To mitigate artifacts from through-plane flow at the locations of steady-state stopbands in balanced steady-state free precession (SSFP) using partial dephasing. A 60° range in the phase accrual during a TR was created over the voxel by slightly unbalancing the slice-select dephaser. The spectral profiles of SSFP with partial dephasing for various constant flow rates and during pulsatile flow were simulated to determine if partial dephasing decreases through-plane flow artifacts originating near SSFP dark bands while maintaining on-resonant signal. Simulations were then validated in a flow phantom. Lastly, phase-cycled SSFP cardiac cine images were acquired with and without partial dephasing in six subjects. Partial dephasing decreased the strength and non-linearity of the dependence of the signal at the stopbands on the through-plane flow rate. It thus mitigated hyper-enhancement from out-of-slice signal contributions and transient-related artifacts caused by variable flow both in the phantom and in vivo. In six volunteers, partial dephasing noticeably decreased artifacts in all of the phase-cycled cardiac cine datasets. Partial dephasing can mitigate the flow artifacts seen at the stopbands in balanced SSFP while maintaining the sequence's desired signal. By mitigating hyper-enhancement and transient-related artifacts originating from the stopbands, partial dephasing facilitates robust multiple-acquisition phase-cycled SSFP in the heart. Magn Reson Med 79:2944-2953, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Needles in the Haystack: Finding Content Worth Preparing for Workplace Learning with the KEP Model

ERIC Educational Resources Information Center

Thalmann, Stefan; Maier, Ronald

2017-01-01

Knowledge transfer between employees is a primary concern in organizations. Employees create or acquire content that partially represents knowledge. These knowledge elements are specific to the context in and for which they are created and rarely address the learning needs of other employees in other work situations. Organizations therefore need…

Acquisition of Three Word Knowledge Aspects through Reading

ERIC Educational Resources Information Center

Daskalovska, Nina

2016-01-01

A number of studies have shown that second or foreign language learners can acquire vocabulary through reading. The aim of the study was to investigate (a) the effects of reading an authentic novel on the acquisition of 3 aspects of word knowledge: spelling, meaning, and collocation; (b) the influence of reading on the acquisition of partial and…

The role of disability self-concept in adaptation to congenital or acquired disability.

PubMed

Bogart, Kathleen R

2014-02-01

Current theories of adaptation to disability do not address differences in adaptation to congenital or acquired disability. Although people with congenital disabilities are generally assumed to be better adapted than people with acquired disabilities, few studies have tested this, and even fewer have attempted to explain the mechanisms behind these differences. This study tested the proposition that whether a disability is congenital or acquired plays an important role in the development of the disability self-concept (consisting of disability identity and disability self-efficacy), which in turn, affects satisfaction with life. It was predicted that disability self-concept would be better developed among people with congenital, compared with acquired disabilities, predicting greater satisfaction with life in those with acquired conditions. 226 participants with congenital and acquired mobility disabilities completed a cross-sectional online questionnaire measuring satisfaction with life, self-esteem, disability identity, disability self-efficacy, and demographic information. Self-esteem, disability identity, disability self-efficacy, and income were significant predictors of satisfaction with life. Congenital onset predicted higher satisfaction with life; disability identity and disability self-efficacy, but not self-esteem, partially mediated the relationship. Findings highlight the distinction between adaptation to congenital versus acquired disability and the importance of disability self-concept, which are underresearched constructs. Results suggest that rather than attempting to "normalize" individuals with disabilities, health care professionals should foster their disability self-concept. Possible ways to improve disability self-concept are discussed, such as involvement in the disability community and disability pride. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Chairside multi-unit restoration of a quadrant using the new Cerec 3D software.

PubMed

Ender, A; Wiedhahn, K; Mörmann, W H

2003-01-01

The new Cerec 3D design software for inlays and partial and full crowns simplifies work when producing several restorations in one session. Quite significant progress has been achieved, in that the entire row of teeth of a quadrant can be acquired completely and displayed by successively overlapping optical impressions. The digital working model of a quadrant in which all preparations are acquired is the result. The restorations can be designed individually and inserted virtually. Thanks to virtual insertion, the proximal contacts to neighboring restorations can be designed perfectly and all restorations finally designed, milled, and inserted in one sitting. This method provides a significant rationalization effect.

CT reconstruction from portal images acquired during volumetric-modulated arc therapy

NASA Astrophysics Data System (ADS)

Poludniowski, G.; Thomas, M. D. R.; Evans, P. M.; Webb, S.

2010-10-01

Volumetric-modulated arc therapy (VMAT), a form of intensity-modulated arc therapy (IMAT), has become a topic of research and clinical activity in recent years. As a form of arc therapy, portal images acquired during the treatment fraction form a (partial) Radon transform of the patient. We show that these portal images, when used in a modified global cone-beam filtered backprojection (FBP) algorithm, allow a surprisingly recognizable CT-volume to be reconstructed. The possibility of distinguishing anatomy in such VMAT-CT reconstructions suggests that this could prove to be a valuable treatment position-verification tool. Further, some potential for local-tomography techniques to improve image quality is shown.

Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier Diffusion Tensor Imaging.

PubMed

Truong, Trong-Kha; Song, Allen W; Chen, Nan-Kuei

2015-01-01

In most diffusion tensor imaging (DTI) studies, images are acquired with either a partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence, in order to shorten the echo time and increase the signal-to-noise ratio (SNR). However, eddy currents induced by the diffusion-sensitizing gradients can often lead to a shift of the echo in k-space, resulting in three distinct types of artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition and reconstruction scheme, capable of generating high-quality and high-SNR DTI data without eddy current-induced artifacts. This new scheme consists of three components, respectively, addressing the three distinct types of artifacts. First, a k-space energy-anchored DTI sequence is designed to recover eddy current-induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial-Fourier reconstruction is used to eliminate artificial signal elevation (i.e., Type 2 artifact) associated with the conventional partial-Fourier reconstruction. Third, a signal intensity correction is applied to remove artificial signal modulations due to eddy current-induced erroneous T2(∗) -weighting (i.e., Type 3 artifact). These systematic improvements will greatly increase the consistency and accuracy of DTI measurements, expanding the utility of DTI in translational applications where quantitative robustness is much needed.

Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier Diffusion Tensor Imaging

PubMed Central

Truong, Trong-Kha; Song, Allen W.; Chen, Nan-kuei

2015-01-01

In most diffusion tensor imaging (DTI) studies, images are acquired with either a partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence, in order to shorten the echo time and increase the signal-to-noise ratio (SNR). However, eddy currents induced by the diffusion-sensitizing gradients can often lead to a shift of the echo in k-space, resulting in three distinct types of artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition and reconstruction scheme, capable of generating high-quality and high-SNR DTI data without eddy current-induced artifacts. This new scheme consists of three components, respectively, addressing the three distinct types of artifacts. First, a k-space energy-anchored DTI sequence is designed to recover eddy current-induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial-Fourier reconstruction is used to eliminate artificial signal elevation (i.e., Type 2 artifact) associated with the conventional partial-Fourier reconstruction. Third, a signal intensity correction is applied to remove artificial signal modulations due to eddy current-induced erroneous T 2 ∗-weighting (i.e., Type 3 artifact). These systematic improvements will greatly increase the consistency and accuracy of DTI measurements, expanding the utility of DTI in translational applications where quantitative robustness is much needed. PMID:26413505

Paradoxical adipose hyperplasia secondary to cryolipolysis: An underreported entity?

PubMed

Singh, Selina M; Geddes, Elizabeth R C; Boutrous, Sean G; Galiano, Robert D; Friedman, Paul M

2015-08-01

Cryolipolysis is a non-invasive, safe, and effective treatment for localized fat reduction. Paradoxical adipose hyperplasia (PAH) is a rare adverse effect in which patients develop painless, firm, and well-demarcated tissue masses in the treatment areas approximately 3-6 months following cryolipolysis. The incidence of PAH has been estimated at 0.0051% or 1 in 20,000 treated patients. We report two cases of PAH seen in our practice, which may suggest the incidence is greater than previously reported. A 44-year-old man underwent cryolipolysis for unwanted fat in the pectoral region. At 4 month follow-up, the patient had well-demarcated tissue growth in the treatment areas. He elected to undergo additional cryolipolysis treatment to the areas. Two months later, he was found to have further tissue growth in the treatment areas. The patient then underwent corrective treatment with liposuction. A 52-year-old man underwent cryolipolysis for unwanted lower abdominal fat. At one year follow-up, he had a well-demarcated, subcutaneous mass on the lower abdomen corresponding to the treatment site. The patient elected to undergo corrective treatment with liposuction. Adipose tissue samples from the treated and non-treated areas, for control, were collected, processed, and stained to evaluate cellularity and tissue structure. In our practice, the incidence of PAH is 0.47% or 2 in 422 cryolipolysis treatments. This is 100 times greater than the device manufacturer's reported incidence. Histopathologic examination of the subcutaneous tissue mass showed an increased number of adipocytes, fibrosis, and scar tissue in the treated areas when compared to controls. No lipoblasts, a marker of malignant neoplastic proliferation, were identified on the histopathologic examination of the affected tissues. The incidence of PAH is likely underreported. Further investigation is necessary to elucidate its mechanism of action. By understanding the pathogenesis, this rare adverse effect may be avoided, or even utilized as a therapeutic alternative for the treatment of congenital or acquired lipodystrophy. © 2015 Wiley Periodicals, Inc.

Congenital defects of the pericardium.

PubMed

Drury, Nigel E; De Silva, Ravi J; Hall, Roger M O; Large, Stephen R

2007-04-01

Congenital defects of the pericardium are rare, but when they are reported they are frequently associated with other cardiac lesions. We describe a case of partial pericardial defect found incidentally at surgery for closure of an ostium primum atrial septal defect. Proposed mechanisms of pericardial defect development are discussed and we suggest that associations with congenital and acquired heart disease are mostly circumstantial.

Consistency of forest presence and biomass predictions modeled across overlapping spatial and temporal extents

Treesearch

Mark D. Nelson; Sean Healey; W. Keith Moser; J.G. Masek; Warren Cohen

2011-01-01

We assessed the consistency across space and time of spatially explicit models of forest presence and biomass in southern Missouri, USA, for adjacent, partially overlapping satellite image Path/Rows, and for coincident satellite images from the same Path/Row acquired in different years. Such consistency in satellite image-based classification and estimation is critical...

Resonance behavior of atomic and molecular photoionization amplitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherepkov, N. A.; Kuznetsov, V. V.; Semenov, S. K.

The behavior of the partial photoionization amplitudes with a given orbital angular momentum l in the complex plane in resonances is studied. In the autoionization resonances the trajectory of the amplitude in the complex plane corresponds to a circle. With increasing photoelectron energy the amplitude moves about a circle in the counterclockwise direction. The new expressions for the partial amplitudes in the resonance are proposed which are similar to the Fano form but contain the 'partial' profile parameters which are connected with the Fano parameter q by a simple relation. In the giant dipole resonances the amplitudes in the complexmore » plane also move about a circle in the counterclockwise direction provided the Coulomb phase is excluded from the amplitude. In the correlational resonances created by channel interactions with the giant dipole resonance the trajectories of the amplitudes acquire a loop about which the amplitudes move in the counterclockwise direction. Very similar behavior of partial photoionization amplitudes in the complex plane is demonstrated also for the dipole transitions from the K shells of the N{sub 2} molecule in the {sigma}* shape resonance.« less

Spatial frequency domain imaging of burn wounds in a preclinical model of graded burn severity

NASA Astrophysics Data System (ADS)

Nguyen, John Quan; Crouzet, Christian; Mai, Tuan; Riola, Kathleen; Uchitel, Daniel; Liaw, Lih-Huei; Bernal, Nicole; Ponticorvo, Adrien; Choi, Bernard; Durkin, Anthony J.

2013-06-01

Frequent monitoring of early-stage burns is necessary for deciding optimal treatment and management. Both superficial and full thickness burns are relatively easy to diagnose based on clinical observation. In between these two extremes are superficial-partial thickness and deep-partial thickness burns. These burns, while visually similar, differ dramatically in terms of clinical treatment and are known to progress in severity over time. The objective of this study was to determine the potential of spatial frequency domain imaging (SFDI) for noninvasively mapping quantitative changes in chromophore and optical properties that may be an indicative of burn wound severity. A controlled protocol of graded burn severity was developed and applied to 17 rats. SFDI data was acquired at multiple near-infrared wavelengths over a course of 3 h. Burn severity was verified using hematoxylin and eosin histology. From this study, we found that changes in water concentration (edema), deoxygenated hemoglobin concentration, and optical scattering (tissue denaturation) to be statistically significant at differentiating superficial partial-thickness burns from deep-partial thickness burns.

Leveraging EAP-Sparsity for Compressed Sensing of MS-HARDI in (k, q)-Space.

PubMed

Sun, Jiaqi; Sakhaee, Elham; Entezari, Alireza; Vemuri, Baba C

2015-01-01

Compressed Sensing (CS) for the acceleration of MR scans has been widely investigated in the past decade. Lately, considerable progress has been made in achieving similar speed ups in acquiring multi-shell high angular resolution diffusion imaging (MS-HARDI) scans. Existing approaches in this context were primarily concerned with sparse reconstruction of the diffusion MR signal S(q) in the q-space. More recently, methods have been developed to apply the compressed sensing framework to the 6-dimensional joint (k, q)-space, thereby exploiting the redundancy in this 6D space. To guarantee accurate reconstruction from partial MS-HARDI data, the key ingredients of compressed sensing that need to be brought together are: (1) the function to be reconstructed needs to have a sparse representation, and (2) the data for reconstruction ought to be acquired in the dual domain (i.e., incoherent sensing) and (3) the reconstruction process involves a (convex) optimization. In this paper, we present a novel approach that uses partial Fourier sensing in the 6D space of (k, q) for the reconstruction of P(x, r). The distinct feature of our approach is a sparsity model that leverages surfacelets in conjunction with total variation for the joint sparse representation of P(x, r). Thus, our method stands to benefit from the practical guarantees for accurate reconstruction from partial (k, q)-space data. Further, we demonstrate significant savings in acquisition time over diffusion spectral imaging (DSI) which is commonly used as the benchmark for comparisons in reported literature. To demonstrate the benefits of this approach,.we present several synthetic and real data examples.

Identification and Severity Determination of Wheat Stripe Rust and Wheat Leaf Rust Based on Hyperspectral Data Acquired Using a Black-Paper-Based Measuring Method.

PubMed

Wang, Hui; Qin, Feng; Ruan, Liu; Wang, Rui; Liu, Qi; Ma, Zhanhong; Li, Xiaolong; Cheng, Pei; Wang, Haiguang

2016-01-01

It is important to implement detection and assessment of plant diseases based on remotely sensed data for disease monitoring and control. Hyperspectral data of healthy leaves, leaves in incubation period and leaves in diseased period of wheat stripe rust and wheat leaf rust were collected under in-field conditions using a black-paper-based measuring method developed in this study. After data preprocessing, the models to identify the diseases were built using distinguished partial least squares (DPLS) and support vector machine (SVM), and the disease severity inversion models of stripe rust and the disease severity inversion models of leaf rust were built using quantitative partial least squares (QPLS) and support vector regression (SVR). All the models were validated by using leave-one-out cross validation and external validation. The diseases could be discriminated using both distinguished partial least squares and support vector machine with the accuracies of more than 99%. For each wheat rust, disease severity levels were accurately retrieved using both the optimal QPLS models and the optimal SVR models with the coefficients of determination (R2) of more than 0.90 and the root mean square errors (RMSE) of less than 0.15. The results demonstrated that identification and severity evaluation of stripe rust and leaf rust at the leaf level could be implemented based on the hyperspectral data acquired using the developed method. A scientific basis was provided for implementing disease monitoring by using aerial and space remote sensing technologies.

Identification and Severity Determination of Wheat Stripe Rust and Wheat Leaf Rust Based on Hyperspectral Data Acquired Using a Black-Paper-Based Measuring Method

PubMed Central

Ruan, Liu; Wang, Rui; Liu, Qi; Ma, Zhanhong; Li, Xiaolong; Cheng, Pei; Wang, Haiguang

2016-01-01

It is important to implement detection and assessment of plant diseases based on remotely sensed data for disease monitoring and control. Hyperspectral data of healthy leaves, leaves in incubation period and leaves in diseased period of wheat stripe rust and wheat leaf rust were collected under in-field conditions using a black-paper-based measuring method developed in this study. After data preprocessing, the models to identify the diseases were built using distinguished partial least squares (DPLS) and support vector machine (SVM), and the disease severity inversion models of stripe rust and the disease severity inversion models of leaf rust were built using quantitative partial least squares (QPLS) and support vector regression (SVR). All the models were validated by using leave-one-out cross validation and external validation. The diseases could be discriminated using both distinguished partial least squares and support vector machine with the accuracies of more than 99%. For each wheat rust, disease severity levels were accurately retrieved using both the optimal QPLS models and the optimal SVR models with the coefficients of determination (R2) of more than 0.90 and the root mean square errors (RMSE) of less than 0.15. The results demonstrated that identification and severity evaluation of stripe rust and leaf rust at the leaf level could be implemented based on the hyperspectral data acquired using the developed method. A scientific basis was provided for implementing disease monitoring by using aerial and space remote sensing technologies. PMID:27128464

SEGMA: An Automatic SEGMentation Approach for Human Brain MRI Using Sliding Window and Random Forests

PubMed Central

Serag, Ahmed; Wilkinson, Alastair G.; Telford, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Anblagan, Devasuda; Macnaught, Gillian; Semple, Scott I.; Boardman, James P.

2017-01-01

Quantitative volumes from brain magnetic resonance imaging (MRI) acquired across the life course may be useful for investigating long term effects of risk and resilience factors for brain development and healthy aging, and for understanding early life determinants of adult brain structure. Therefore, there is an increasing need for automated segmentation tools that can be applied to images acquired at different life stages. We developed an automatic segmentation method for human brain MRI, where a sliding window approach and a multi-class random forest classifier were applied to high-dimensional feature vectors for accurate segmentation. The method performed well on brain MRI data acquired from 179 individuals, analyzed in three age groups: newborns (38–42 weeks gestational age), children and adolescents (4–17 years) and adults (35–71 years). As the method can learn from partially labeled datasets, it can be used to segment large-scale datasets efficiently. It could also be applied to different populations and imaging modalities across the life course. PMID:28163680

False homozygous HLA genotyping results due to copy number neutral loss of heterozygosity in acquired aplastic anaemia.

PubMed

Heyrman, Bert; De Becker, Ann; Verheyden, Sonja; Demanet, Christian

2017-03-02

The aim of this case report is to draw attention on possible false human leucocyte antigen (HLA) genotyping in acquired aplastic anaemia prior to allogeneic haematopoietic stem cell transplantation. In acquired aplastic anaemia loss of heterozygosity (LOH) of chromosome 6p is known to occur in around 12%. We report false HLA genotyping results due to LOH and a coinciding steep rise in neutrophils following filgrastim stimulation in a patient with very severe aplastic anaemia. At diagnosis we obtained heterozygous results on peripheral blood. Failing to reach a partial response at 6 months with immune-suppressive therapy we repeated HLA genotyping, obtaining homozygous results. Repeated testing confirmed loss of HLA genotype heterozygosity. HLA genotyping on cells obtained by a buccal swab confirmed the previous HLA heterozygosity. A second course of filgrastim at the time of homozygous HLA genotyping resulted in a steep rise in neutrophils. Stopping filgrastim resulted in an equally steep drop. 2017 BMJ Publishing Group Ltd.

77 FR 51107 - Mineral Range, Inc.-Acquisition and Operation Exemption-Rail Line of Lake Superior & Ishpeming...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-23

..., Inc. (MRI), a noncarrier, has filed a verified notice of exemption under 49 CFR 1150.31 to acquire...). MRI now seeks to reinstitute rail service over Segment 2 as a successor in interest to LSI, an action... recreational trail and is not at issue here.\\1\\ \\1\\ MRI simultaneously filed a petition for partial vacation of...

Evaluation and Management of Dyslipidemia in Patients with HIV Infection

PubMed Central

Green, Michael L

2002-01-01

OBJECTIVE Persons with HIV infection develop metabolic abnormalities related to their antiretroviral therapy and HIV infection itself. The objective of this study was to summarize the emerging evidence for the incidence, etiology, health risks, and treatment of dyslipidemias in HIV disease. DESIGN Systematic review of original research with quantitative synthesis. MAIN RESULTS Dyslipidemia is common in persons with HIV infection on highly active antiretroviral therapy (HAART), but methodologic differences between studies preclude precise estimates of prevalence and incidence. The typical pattern includes elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides, which may be markedly elevated. The dyslipidemia may be associated with lipodystrophy, insulin resistance, and, rarely, frank diabetes mellitus. Exposure to protease inhibitors (PIs) is associated with this entire range of metabolic abnormalities. PI-naïve patients on nucleoside reverse transcriptase inhibitors (NRTIs) may develop lipodystrophy, insulin resistance, hypercholesterolemia, and possibly modest elevations in triglycerides but not severe hypertriglyceridemia, which appears to be linked to PIs alone. Most studies have not found an association between CD4 lymphocyte count or HIV viral load and lipid abnormalities. The pathogenesis is incompletely understood and appears to be multifactorial. There are insufficient data to definitively support an increased coronary heart disease risk in patients with HIV-related dyslipidemia. However, some of the same metabolic abnormalities remain firmly established risk factors in other populations. Patients on HAART with severe hypertriglyceridemia may develop pancreatitis or other manifestations of the chylomicronemia syndrome. Some of the metabolic derangements (particularly hypertriglyceridemia) may improve upon replacing a PI with a non-nucleoside reverse transcriptase inhibitor. The limited experience suggests that fibrates, pravastatin, and atorvastatin can safely treat lipid abnormalities in HIV-infected patients. CONCLUSIONS Patients with HIV infection on HAART should be screened for lipid disorders, given their incidence, potential for morbidity, and possible long-term cardiovascular risk. Treatment decisions are complex and must include assessments of cardiac risk, HIV infection status, reversibility of the dyslipidemia, and the effectiveness and toxicities of lipid-lowering medications. The multiple potential drug interactions with antiretroviral or other HIV-related medications should be considered in lipid-lowering drug selection and monitoring. PMID:12390557

Cardiovascular risk and dyslipidemia among persons living with HIV: a review.

PubMed

Maggi, Paolo; Di Biagio, Antonio; Rusconi, Stefano; Cicalini, Stefania; D'Abbraccio, Maurizio; d'Ettorre, Gabriella; Martinelli, Canio; Nunnari, Giuseppe; Sighinolfi, Laura; Spagnuolo, Vincenzo; Squillace, Nicola

2017-08-09

Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

PubMed

Masuka, Josiah T; Chipangura, Precious; Nyambayo, Priscilla P; Stergachis, Andy; Khoza, Star

2018-01-01

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for psychosis. There is a need to carefully manage TB/HIV co-infected patients, due to the higher risk of adverse drug reactions which may lead to poor treatment adherence and outcomes.

Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization.

PubMed

Brier, Matthew R; Mitra, Anish; McCarthy, John E; Ances, Beau M; Snyder, Abraham Z

2015-11-01

Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Partial covariance based functional connectivity computation using Ledoit-Wolf covariance regularization

PubMed Central

Brier, Matthew R.; Mitra, Anish; McCarthy, John E.; Ances, Beau M.; Snyder, Abraham Z.

2015-01-01

Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a complicated covariance structure. Partial covariance assesses the unique variance shared between two brain regions excluding any widely shared variance, hence is appropriate for the analysis of multivariate fMRI datasets. However, calculation of partial covariance requires inversion of the covariance matrix, which, in most functional connectivity studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf shrinkage (L2 regularization) to invert the high dimensional BOLD covariance matrix. We investigate the network organization and brain-state dependence of partial covariance-based functional connectivity. Although RSNs are conventionally defined in terms of shared variance, removal of widely shared variance, surprisingly, improved the separation of RSNs in a spring embedded graphical model. This result suggests that pair-wise unique shared variance plays a heretofore unrecognized role in RSN covariance organization. In addition, application of partial correlation to fMRI data acquired in the eyes open vs. eyes closed states revealed focal changes in uniquely shared variance between the thalamus and visual cortices. This result suggests that partial correlation of resting state BOLD time series reflect functional processes in addition to structural connectivity. PMID:26208872

Road Signs Detection and Recognition Utilizing Images and 3d Point Cloud Acquired by Mobile Mapping System

NASA Astrophysics Data System (ADS)

Li, Y. H.; Shinohara, T.; Satoh, T.; Tachibana, K.

2016-06-01

High-definition and highly accurate road maps are necessary for the realization of automated driving, and road signs are among the most important element in the road map. Therefore, a technique is necessary which can acquire information about all kinds of road signs automatically and efficiently. Due to the continuous technical advancement of Mobile Mapping System (MMS), it has become possible to acquire large number of images and 3d point cloud efficiently with highly precise position information. In this paper, we present an automatic road sign detection and recognition approach utilizing both images and 3D point cloud acquired by MMS. The proposed approach consists of three stages: 1) detection of road signs from images based on their color and shape features using object based image analysis method, 2) filtering out of over detected candidates utilizing size and position information estimated from 3D point cloud, region of candidates and camera information, and 3) road sign recognition using template matching method after shape normalization. The effectiveness of proposed approach was evaluated by testing dataset, acquired from more than 180 km of different types of roads in Japan. The results show a very high success in detection and recognition of road signs, even under the challenging conditions such as discoloration, deformation and in spite of partial occlusions.

Evaluation of Dietary Intake, Leisure-Time Physical Activity, and Metabolic Profile in Women with Mutation in the LMNA Gene.

PubMed

Monteiro, Luciana; Foss-Freitas, Maria Cristina; Navarro, Anderson; Pereira, Francisco; Coeli, Fernanda; Carneseca, Estela; Júnior, Renan Montenegro; Foss, Milton

2017-01-01

Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat, which is associated with insulin-resistant diabetes. The Dunnigan variety (FPLD2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. The aim of this study was to assess and compare the dietary intake, leisure-time physical activity (LTPA), and biochemical measurements (glucose, A1C, and plasma lipids) in women with FPLD2 and without (control group, CG) and to examine the associations between dietary intake and biochemical measurements (BM). LTPA was measured with a questionnaire and metabolic equivalent (MET) hours per week (hours/week) were calculated. Dietary intake by the 3-day recall method and clinical laboratory parameters were collected. Characteristics of women with FPLD2: 35.8 ± 13.9 years, fat mass = 10 ± 2.3 kg and fat free mass = 41.4 ± 4.5 kg (p < 0.05). Women with FPLD2 showed a smaller intake of energy (kcal), lipids, and carbohydrates and a large intake of protein (p < 0.01) compared to CG. Comparing the 2 groups in terms of LTPA, 78% of women with FPLD2 performed insufficient physical activity. In addition, they had a higher levels of glucose, A1C, and triglycerides (TG) and lower levels of high-density lipoprotein (HDL). There was no correlation between dietary intake and biochemical measurements. Women with FPLD2 have a lower intake of energy (kcal), lipids, and carbohydrates and greater changes in biochemical measurements. Because this is a rare disease, future studies are needed with encouragement of the practice of physical activity and of healthy eating habits, preventing the onset of diseases.

Partially confined configuration for the growth of semiconductor crystals from the melt in zero-gravity environment

NASA Technical Reports Server (NTRS)

Lagowski, J.; Gatos, H. C.; Dabkowski, F. P.

1985-01-01

A novel partially confined configuration is proposed for the crystal growth of semiconductors from the melt, including those with volatile constituents. A triangular prism is employed to contain the growth melt. Due to surface tension, the melt will acquire a cylindrical-like shape and thus contact the prism along three parallel lines. The three empty spaces between the cylindrical melt and the edges of the prism will accommodate the expansion of the solidifying semiconductor, and in the case of semiconductor compounds with a volatile constituent, will permit the presence of the desired vapor phase in contact with the melt for controlling the melt stoichiometry. Theoretical and experimental evidence in support of this new type of confinement is presented.

[Utility of atazanavir in special populations].

PubMed

Antela López, Antonio

2008-12-01

ART (antiretroviral therapy) currently continues to indefinitely prolong the survival of patients who live with HIV. Due to this, we are increasingly faced with specific problems that previously did not have time to develop or did not have the importance that they have now, and which are related to the existence of special patient populations. Examples of situations that characterise these special populations are: co-infection with hepatitis virus B and/or C, pregnancy, lipodystrophy, cardiovascular risk, renal failure, treatment of children and adolescents, immigrant health care, and the management of patients receiving methadone replacement therapy, among others. In this article we review the role that Atazanavir (ATV) can play in the ART of patients in the situations mentioned, except those that are already dealt with specifically in other articles, such as co-infection by hepatitis virus B and/or C.

Evaluation of Alternative Means of Implementing Section 1362 of the National Flood Insurance Act of 1968.

DTIC Science & Technology

1981-03-01

Near the Regulated Floodplain. Research paper submitted in partial fulfillment of the requirements for the deuree of Master of Science , Dept. of...discretionary funds, and private corporations and foundations . 17. Soldiers Grove, Wisconsin. The city has begun to acquire its central business...for single-farily homes) * Data on Federal Disaster relief expenditures analyzed for this study ** Estimated average acturial rate of critical

The Systemic Acquired Resistance Regulator OsNPR1 Attenuates Growth by Repressing Auxin Signaling through Promoting IAA-Amido Synthase Expression1[OPEN

PubMed Central

2016-01-01

Systemic acquired resistance is a long-lasting and broad-spectrum disease resistance to pathogens. Our previous study demonstrated that overexpression of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (OsNPR1), a master gene for systemic acquired resistance in rice (Oryza sativa), greatly enhanced resistance to bacterial blight caused by Xanthomonas oryzae pv oryzae. However, the growth and development of the OsNPR1 overexpression (OsNPR1-OX) plants were restrained, and the mechanism remained elusive. In this study, we dissected the OsNPR1-induced growth inhibition. We found that the OsNPR1-OX lines displayed phenotypes mimicking auxin-defective mutants, with decreases in root system, seed number and weight, internode elongation, and tiller number. Whole-genome expression analysis revealed that genes related to the auxin metabolism and signaling pathway were differentially expressed between the OsNPR1-OX and wild-type plants. Consistently, the indole-3-acetic acid (IAA) content was decreased and the auxin distribution pattern was altered in OsNPR1-OX plants. Importantly, we found that some GH3 family members, in particular OsGH3.8 coding IAA-amido synthetase, were constitutively up-regulated in OsNPR1-OX plants. Decreased OsGH3.8 expression by RNA interference could partially restore IAA level and largely rescue the restrained growth and development phenotypes but did not affect the disease resistance of OsNPR1-OX plants. Taken together, we revealed that OsNPR1 affects rice growth and development by disrupting the auxin pathway at least partially through indirectly up-regulating OsGH3.8 expression. PMID:27378815

Failure of colostral immunoglobulin transfer as an explanation for most infections and deaths of neonatal foals.

PubMed

McGuire, T C; Crawford, T B; Hallowell, A L; Macomber, L E

1977-06-01

Failure in colostral immunoglobulin G (IgG) transfer was found in 9 of 87 Thoroughbred foals. Seven (78%) of these 9 foals acquired infections requiring therapy. Twelve of the foals had partial failure in colostral IgG transfer, and 3 of these had infections requiring therapy. The remaining 66 foals had normal transfer of colostral IgG, and only 2 had detectable infections. The failure of colostral IgG transfer was attributable to nursing problems in only one case. When presuckle postpartum colostrum was collected, 2 of 4 failures of colostral IgG transfer and 4 of 6 partial failures of colostral IgG transfer were explained by low colostral IgG content. Of 11 foals from various other sources and dying of infection before 2 weeks of age, 6 had failure of colostral IgG transfer (less than 200 mg IgG/100 ml serum), and 4 had partial failure (200-400 mg IgG/100 ml serum).

Acquired dysfibrinogenemia secondary to multiple myeloma.

PubMed

Kotlín, Roman; Sobotková, Alzbeta; Riedel, Tomás; Salaj, Peter; Suttnar, Jirí; Reicheltová, Zuzana; Májek, Pavel; Khaznadar, Tarek; Dyr, Jan E

2008-01-01

Abnormal coagulation properties indicative of a dysfibrinogen were found in the plasma of a 72-year-old male with multiple myeloma (IgGkappa, stage IIIA). The patient had high paraprotein concentration (85.75 g/l) and prolonged thrombin time (76.8 s), activated partial thromboplastin time (39.5 s), prothrombin time (23.5 s) and reptilase time (72.0 s). The fibrinogen level was increased. The fibrin polymerization induced by both thrombin and reptilase was impaired. Scanning electron microscopy revealed abnormal clot morphology. After six months of treatment, the paraprotein level decreased (19.48 g/l) and coagulation normalized as well as fibrin polymerization and fibrin clot morphology. It was found that the paraprotein interacts with the gamma-chain of fibrinogen. Acquired dysfibrinogenemia associated with multiple myeloma was diagnosed in the 72-year-old patient.

A software tool for automatic classification and segmentation of 2D/3D medical images

NASA Astrophysics Data System (ADS)

Strzelecki, Michal; Szczypinski, Piotr; Materka, Andrzej; Klepaczko, Artur

2013-02-01

Modern medical diagnosis utilizes techniques of visualization of human internal organs (CT, MRI) or of its metabolism (PET). However, evaluation of acquired images made by human experts is usually subjective and qualitative only. Quantitative analysis of MR data, including tissue classification and segmentation, is necessary to perform e.g. attenuation compensation, motion detection, and correction of partial volume effect in PET images, acquired with PET/MR scanners. This article presents briefly a MaZda software package, which supports 2D and 3D medical image analysis aiming at quantification of image texture. MaZda implements procedures for evaluation, selection and extraction of highly discriminative texture attributes combined with various classification, visualization and segmentation tools. Examples of MaZda application in medical studies are also provided.

MRI-guided brain PET image filtering and partial volume correction

NASA Astrophysics Data System (ADS)

Yan, Jianhua; Chu-Shern Lim, Jason; Townsend, David W.

2015-02-01

Positron emission tomography (PET) image quantification is a challenging problem due to limited spatial resolution of acquired data and the resulting partial volume effects (PVE), which depend on the size of the structure studied in relation to the spatial resolution and which may lead to over or underestimation of the true tissue tracer concentration. In addition, it is usually necessary to perform image smoothing either during image reconstruction or afterwards to achieve a reasonable signal-to-noise ratio. Typically, an isotropic Gaussian filtering (GF) is used for this purpose. However, the noise suppression is at the cost of deteriorating spatial resolution. As hybrid imaging devices such as PET/MRI have become available, the complementary information derived from high definition morphologic images could be used to improve the quality of PET images. In this study, first of all, we propose an MRI-guided PET filtering method by adapting a recently proposed local linear model and then incorporate PVE into the model to get a new partial volume correction (PVC) method without parcellation of MRI. In addition, both the new filtering and PVC are voxel-wise non-iterative methods. The performance of the proposed methods were investigated with simulated dynamic FDG brain dataset and 18F-FDG brain data of a cervical cancer patient acquired with a simultaneous hybrid PET/MR scanner. The initial simulation results demonstrated that MRI-guided PET image filtering can produce less noisy images than traditional GF and bias and coefficient of variation can be further reduced by MRI-guided PET PVC. Moreover, structures can be much better delineated in MRI-guided PET PVC for real brain data.

Hidden physics models: Machine learning of nonlinear partial differential equations

NASA Astrophysics Data System (ADS)

Raissi, Maziar; Karniadakis, George Em

2018-03-01

While there is currently a lot of enthusiasm about "big data", useful data is usually "small" and expensive to acquire. In this paper, we present a new paradigm of learning partial differential equations from small data. In particular, we introduce hidden physics models, which are essentially data-efficient learning machines capable of leveraging the underlying laws of physics, expressed by time dependent and nonlinear partial differential equations, to extract patterns from high-dimensional data generated from experiments. The proposed methodology may be applied to the problem of learning, system identification, or data-driven discovery of partial differential equations. Our framework relies on Gaussian processes, a powerful tool for probabilistic inference over functions, that enables us to strike a balance between model complexity and data fitting. The effectiveness of the proposed approach is demonstrated through a variety of canonical problems, spanning a number of scientific domains, including the Navier-Stokes, Schrödinger, Kuramoto-Sivashinsky, and time dependent linear fractional equations. The methodology provides a promising new direction for harnessing the long-standing developments of classical methods in applied mathematics and mathematical physics to design learning machines with the ability to operate in complex domains without requiring large quantities of data.

Correlation between hepatobiliary scintigraphy and surgery or postmortem examination findings in dogs and cats with extrahepatic biliary obstruction, partial obstruction, or patency of the biliary system: 18 cases (1995-2004).

PubMed

Head, Laurie L; Daniel, Gregory B

2005-11-15

To evaluate the usefulness of serum biochemical variables and scintigraphic study results for differentiating between dogs and cats with complete extrahepatic biliary obstruction (EHO) and those with partial EHO or patent bile ducts. Retrospective case series. 17 dogs and 1 cat. Animals that underwent hepatobiliary scintigraphy and had either surgical or postmortem confirmation of the degree of bile duct patency were included. Scintigraphic images were evaluated and biliary tracts were classified as patent, partially obstructed but patent, or obstructed. Surgery or postmortem examination was considered the gold standard for diagnosis, and compared with those findings, sensitivity and specificity of scintigraphy were calculated. With absence of radioactivity in the intestinal tract as the diagnostic criterion for EHO, the sensitivity and specificity of scintigraphic diagnosis were both 83% when final images were acquired at 19 to 24 hours, compared with 100% and 33%, respectively, when 180 minutes was used as the cutoff time. Animals with partial biliary obstruction had less intestinal radioactivity that arrived later than that observed in animals with patent biliary tracts. Animals in which intestinal radioactivity has not been observed after the standard 3 to 4 hours should undergo additional scintigraphic imaging. Findings in animals with partial biliary obstruction include delayed arrival of radioactivity and less radioactivity in the intestine. Distinguishing between complete and partial biliary tract obstruction is important because animals with partial obstruction may respond favorably to medical management and should not be given an erroneous diagnosis of complete obstruction.

Hexagonal undersampling for faster MRI near metallic implants.

PubMed

Sveinsson, Bragi; Worters, Pauline W; Gold, Garry E; Hargreaves, Brian A

2015-02-01

Slice encoding for metal artifact correction acquires a three-dimensional image of each excited slice with view-angle tilting to reduce slice and readout direction artifacts respectively, but requires additional imaging time. The purpose of this study was to provide a technique for faster imaging around metallic implants by undersampling k-space. Assuming that areas of slice distortion are localized, hexagonal sampling can reduce imaging time by 50% compared with conventional scans. This work demonstrates this technique by comparisons of fully sampled images with undersampled images, either from simulations from fully acquired data or from data actually undersampled during acquisition, in patients and phantoms. Hexagonal sampling is also shown to be compatible with parallel imaging and partial Fourier acquisitions. Image quality was evaluated using a structural similarity (SSIM) index. Images acquired with hexagonal undersampling had no visible difference in artifact suppression from fully sampled images. The SSIM index indicated high similarity to fully sampled images in all cases. The study demonstrates the ability to reduce scan time by undersampling without compromising image quality. © 2014 Wiley Periodicals, Inc.

Comparison of pre/post-operative CT image volumes to preoperative digitization of partial hepatectomies: a feasibility study in surgical validation

NASA Astrophysics Data System (ADS)

Dumpuri, Prashanth; Clements, Logan W.; Li, Rui; Waite, Jonathan M.; Stefansic, James D.; Geller, David A.; Miga, Michael I.; Dawant, Benoit M.

2009-02-01

Preoperative planning combined with image-guidance has shown promise towards increasing the accuracy of liver resection procedures. The purpose of this study was to validate one such preoperative planning tool for four patients undergoing hepatic resection. Preoperative computed tomography (CT) images acquired before surgery were used to identify tumor margins and to plan the surgical approach for resection of these tumors. Surgery was then performed with intraoperative digitization data acquire by an FDA approved image-guided liver surgery system (Pathfinder Therapeutics, Inc., Nashville, TN). Within 5-7 days after surgery, post-operative CT image volumes were acquired. Registration of data within a common coordinate reference was achieved and preoperative plans were compared to the postoperative volumes. Semi-quantitative comparisons are presented in this work and preliminary results indicate that significant liver regeneration/hypertrophy in the postoperative CT images may be present post-operatively. This could challenge pre/post operative CT volume change comparisons as a means to evaluate the accuracy of preoperative surgical plans.

Berardinelli–Seip syndrome: highlight of treatment challenge

PubMed Central

Ferraria, Nélia; Pedrosa, Cristina; Amaral, Daniela; Lopes, Lurdes

2013-01-01

Berardinelli–Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal-recessive disease characterised by lipoatrophy and associated with deregulations of glycidic and lipid metabolism. We report three BSCL cases with its typical clinical picture and complications. Clinically, they all show marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. Two cases present attention deficit hyperactivity and developmental learning disorders; another patient has hypertrophic myocardiopathy and polycystic ovary syndrome. In all the cases AGPAT2 was the identified mutation. All the cases present hypertriglyceridemia. One case has developed hyperinsulinism controlled with metformin and another case already has type 2 diabetes with a difficult clinical control. There is no curative treatment and the current treatment options are based only on symptomatic control of the complications. Recently, published studies showed that leptin-replacement therapy appears a promising tool in the metabolic correction of BSCL complications, highlighting the importance of further investigations in BSCL treatment. PMID:23362058

Lipotoxicity, fatty acid uncoupling and mitochondrial carrier function.

PubMed

Rial, Eduardo; Rodríguez-Sánchez, Leonor; Gallardo-Vara, Eunate; Zaragoza, Pilar; Moyano, Eva; González-Barroso, M Mar

2010-01-01

Diseases like obesity, diabetes or generalized lipodystrophy cause a chronic elevation of circulating fatty acids that can become cytotoxic, a condition known as lipotoxicity. Fatty acids cause oxidative stress and alterations in mitochondrial structure and function. The uncoupling of the oxidative phosphorylation is one of the most recognized deleterious fatty acid effects and several metabolite transporters are known to mediate in their action. The fatty acid interaction with the carriers leads to membrane depolarization and/or the conversion of the carrier into a pore. The result is the opening of the permeability transition pore and the initiation of apoptosis. Unlike the other members of the mitochondrial carrier superfamily, the eutherian uncoupling protein UCP1 has evolved to achieve its heat-generating capacity in the physiological context provided by the brown adipocyte and therefore it is activated by the low fatty acid concentrations generated by the noradrenaline-stimulated lipolysis. Copyright © 2010 Elsevier B.V. All rights reserved.

Pancreatic Islet Responses to Metabolic Trauma

PubMed Central

Burke, Susan J.; Karlstad, Michael D.; Collier, J. Jason

2016-01-01

Carbohydrate, lipid, and protein metabolism are largely controlled by the interplay of various hormones, which includes those secreted by the pancreatic islets of Langerhans. While typically representing only 1–2% of the total pancreatic mass, the islets have a remarkable ability to adapt to disparate situations demanding a change in hormone release, such as peripheral insulin resistance. There are many different routes to the onset of insulin resistance, including obesity, lipodystrophy, glucocorticoid excess, and the chronic usage of atypical anti-psychotic drugs. All of these situations are coupled to an increase in pancreatic islet size, often with a corresponding increase in insulin production. These adaptive responses within the islets are ultimately intended to maintain glycemic control and to promote macronutrient homeostasis during times of stress. Herein, we review the consequences of specific metabolic trauma that lead to insulin resistance and the corresponding adaptive alterations within the pancreatic islets. PMID:26974425

The nuclear lamina in health and disease.

PubMed

Dobrzynska, Agnieszka; Gonzalo, Susana; Shanahan, Catherine; Askjaer, Peter

2016-05-03

The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases.

Juvenile Dermatomyositis: Key Roles of Muscle Magnetic Resonance Imaging and Early Aggressive Treatment.

PubMed

Corral-Magaña, O; Bauzá-Alonso, A F; Escudero-Góngora, M M; Lacruz, L; Martín-Santiago, A

2017-09-12

Juvenile dermatomyositis is a rare systemic connective tissue disease with onset during childhood. It presents clinically with proximal muscle weakness and characteristic skin involvement. Diagnosis is based on the Bohan and Peter criteria, though many authors are now substituting biopsy with muscle magnetic resonance imaging (MRI) for both diagnosis and follow-up. Without intensive early treatment, complications such as calcinosis cutis and lipodystrophy can develop in the chronic phases of the disease. Early recognition is therefore key to management. We present a series of 5 patients who were diagnosed with Juvenile dermatomyositis on muscle MRI without undergoing muscle biopsy and who received early treatment. We draw attention to the usefulness of muscle MRI for the diagnosis of muscle involvement and to the importance of early initiation of intensive treatment to prevent complications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

[HIV infection in France in 2012: reality, risks and challenges for a chronic multisystem disease].

PubMed

Blot, M; Piroth, L

2012-06-01

Thirty years after the discovery of HIV and 15 years since the advent of Highly Active Antiretroviral Therapy (HAART), the features of HIV infection have evolved and need a new approach, which is both more comprehensive and specialized. Indeed, the burden of a chronic disease with multiple determining features has replaced the rapidly fatal infection of the past, which was almost exclusively related to the effects of immunosuppression. Physicians have to be concerned with "new risks" associated with treatment side effects; the consequences of ongoing inflammation and ageing of the HIV-infected population. These include metabolic, cardiovascular, neurocognitive and renal disease as well as lipodystrophy and malignancy. Antiretroviral treatment has been a major step forward, subject to accessibility, tolerance and adherence, but it has not solved all the problems associated with this infection, as it becomes a chronic illness. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes?

PubMed

Mansilla, Eduardo; Díaz Aquino, Vanina; Zambón, Daniel; Marin, Gustavo Horacio; Mártire, Karina; Roque, Gustavo; Ichim, Thomas; Riordan, Neil H; Patel, Amit; Sturla, Flavio; Larsen, Gustavo; Spretz, Rubén; Núñez, Luis; Soratti, Carlos; Ibar, Ricardo; van Leeuwen, Michiel; Tau, José María; Drago, Hugo; Maceira, Alberto

2011-01-01

One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.

Could Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?

PubMed Central

Mansilla, Eduardo; Díaz Aquino, Vanina; Zambón, Daniel; Marin, Gustavo Horacio; Mártire, Karina; Roque, Gustavo; Ichim, Thomas; Riordan, Neil H.; Patel, Amit; Sturla, Flavio; Larsen, Gustavo; Spretz, Rubén; Núñez, Luis; Soratti, Carlos; Ibar, Ricardo; van Leeuwen, Michiel; Tau, José María; Drago, Hugo; Maceira, Alberto

2011-01-01

One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies. PMID:21716667

Metabolic effects of the HIV protease inhibitor--saquinavir in differentiating human preadipocytes.

PubMed

Bociąga-Jasik, Monika; Polus, Anna; Góralska, Joanna; Czech, Urszula; Gruca, Anna; Śliwa, Agnieszka; Garlicki, Aleksander; Mach, Tomasz; Dembińska-Kieć, Aldona

2013-01-01

The iatrogenic, HIV-related lipodystrophy is associated with development of the significant metabolic and cardiovascular complications. The underlying mechanisms of antiretroviral (ARV) drugs are not completely explored. The aim of the study was to characterize effects of the protease inhibitor (PI)--saquinavir (SQV) on metabolic functions, and gene expression during differentiation in cells (Chub-S7) culture. SQV in concentrations observed during antiretroviral therapy (ART) significantly decreased mitochondrial membrane potential (MMP), oxygen consumption and ATP generation. The effects were greater in already differentiated cells. This was accompanied by characteristic changes in the expression of the genes involved in endoplasmic reticulum (ER) stress, and differentiation (lipid droplet formation) process such as: WNT10a, C/EBPa, AFT4, CIDEC, ADIPOQ, LPIN1. The results indicate that SQV affects not only metabolic (mitochondrial) activity of adipocytes, but affects the expression of genes related to differentiation and to a lesser extent to cell apoptosis.

Bone disorders associated with the human immunodeficiency virus: pathogenesis and management.

PubMed

Qaqish, Roula B; Sims, Keri A

2004-10-01

Bone disorders such as osteopenia, osteoporosis, and osteonecrosis have been reported in patients infected with the human immunodeficiency virus (HIV), but the etiology and mechanism of these disorders are unknown. The prevalence estimates vary widely among studies and may be influenced by the presence or absence of antiretroviral therapy and lipodystrophy, severity of HIV disease, and overlapping bone loss risk factors. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in patients with HIV who have risks for bone disease are important strategies in preventing osteopenia and osteoporosis in HIV-infected patients. Management of osteopenia and osteoporosis is still being evaluated. Administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be reasonable in treating osteoporosis; however, surgical intervention is the only method for treating symptomatic osteonecrosis.

Modelling acquired dyslexia: a software tool for developing grapheme-phoneme correspondences.

PubMed Central

D'Autrechy, C. L.; Reggia, J. A.; Berndt, R. S.

1991-01-01

In extending a computer model of acquired dyslexia, it has become necessary to develop a way to group printed characters in a word so that the character groups essentially have a one-to-one correspondence with the word's phonemes (speech sounds). This requires deriving a set of correspondences (legal character groupings, legal associations of character groups with phonemes, etc.) that yield a single grouping or "segmentation" of characters when applied to any English word. To facilitate and partially automate this task, a segmentation program has been developed that uses an interchangeable set of correspondences. The program segments words according to these correspondences and tabulates their success over large sets of words. The program has been used successfully to segment a 20,000 word corpus, demonstrating that this approach can be used effectively and efficiently. PMID:1807611

A New Model of Jupiter's Magnetic Field From Juno's First Nine Orbits

NASA Astrophysics Data System (ADS)

Connerney, J. E. P.; Kotsiaros, S.; Oliversen, R. J.; Espley, J. R.; Joergensen, J. L.; Joergensen, P. S.; Merayo, J. M. G.; Herceg, M.; Bloxham, J.; Moore, K. M.; Bolton, S. J.; Levin, S. M.

2018-03-01

A spherical harmonic model of the magnetic field of Jupiter is obtained from vector magnetic field observations acquired by the Juno spacecraft during its first nine polar orbits about the planet. Observations acquired during eight of these orbits provide the first truly global coverage of Jupiter's magnetic field with a coarse longitudinal separation of 45° between perijoves. The magnetic field is represented with a degree 20 spherical harmonic model for the planetary ("internal") field, combined with a simple model of the magnetodisc for the field ("external") due to distributed magnetospheric currents. Partial solution of the underdetermined inverse problem using generalized inverse techniques yields a model ("Juno Reference Model through Perijove 9") of the planetary magnetic field with spherical harmonic coefficients well determined through degree and order 10, providing the first detailed view of a planetary dynamo beyond Earth.

Partial 'Seminole' Panorama (False Color)

NASA Technical Reports Server (NTRS)

2005-01-01

This view from Spirit's panoramic camera is assembled from frames acquired on Martian days, or sols, 672 and 673 (Nov. 23 and 24, 2005) from the rover's position near an outcrop called 'Seminole.' The view is a southward-looking portion of a larger panorama still being completed. This is a false-color version to emphasize geological differences. It is a composite of images shot through three different filters, admitting light of wavelengths 750 nanometers, 530 nanometers and 430 nanometers.

Technique for bone volume measurement from human femur head samples by classification of micro-CT image histograms.

PubMed

Marinozzi, Franco; Bini, Fabiano; Marinozzi, Andrea; Zuppante, Francesca; De Paolis, Annalisa; Pecci, Raffaella; Bedini, Rossella

2013-01-01

Micro-CT analysis is a powerful technique for a non-invasive evaluation of the morphometric parameters of trabecular bone samples. This elaboration requires a previous binarization of the images. A problem which arises from the binarization process is the partial volume artifact. Voxels at the external surface of the sample can contain both bone and air so thresholding operates an incorrect estimation of volume occupied by the two materials. The aim of this study is the extraction of bone volumetric information directly from the image histograms, by fitting them with a suitable set of functions. Nineteen trabecular bone samples were extracted from femoral heads of eight patients subject to a hip arthroplasty surgery. Trabecular bone samples were acquired using micro-CT Scanner. Hystograms of the acquired images were computed and fitted by Gaussian-like functions accounting for: a) gray levels produced by the bone x-ray absorption, b) the portions of the image occupied by air and c) voxels that contain a mixture of bone and air. This latter contribution can be considered such as an estimation of the partial volume effect. The comparison of the proposed technique to the bone volumes measured by a reference instrument such as by a helium pycnometer show the method as a good way for an accurate bone volume calculation of trabecular bone samples.

Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

PubMed Central

Petoumenos, Kathy; Worm, Signe W; Fontas, Eric; Weber, Rainer; De Wit, Stephane; Bruyand, Mathias; Reiss, Peter; El-Sadr, Wafaa; Monforte, Antonella D'Arminio; Friis-Møller, Nina; Lundgren, Jens D; Law, Matthew G

2012-01-01

Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2. Conclusions The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham. PMID:23078769

Sphaeridiotrema globulus and Sphaeridiotrema pseudoglobulus (Digenea): Species Differentiation Based On mtDNA (Barcode) and Partial LSU–rDNA Sequences

USGS Publications Warehouse

Bergmame, Laura; Huffman, Jane; Cole, Rebecca; Dayanandan, Selvadurai; Tkach, Vasyl; McLaughlin, J. Daniel

2011-01-01

Flukes belonging to Sphaeridiotrema are important parasites of waterfowl, and 2 morphologically similar species Sphaeridiotrema globulus and Sphaeridiotrema pseudoglobulus, have been implicated in waterfowl mortality in North America. Cytochrome oxidase I (barcode region) and partial LSU-rDNA sequences from specimens of S. globulus and S. pseudoglobulus, obtained from naturally and experimentally infected hosts from New Jersey and Quebec, respectively, confirmed that these species were distinct. Barcode sequences of the 2 species differed at 92 of 590 nucleotide positions (15.6%) and the translated sequences differed by 13 amino acid residues. Partial LSU-rDNA sequences differed at 29 of 1,208 nucleotide positions (2.4%). Additional barcode sequences from specimens collected from waterfowl in Wisconsin and Minnesota and morphometric data obtained from specimens acquired along the north shore of Lake Superior revealed the presence of S. pseudoglobulus in these areas. Although morphometric data suggested the presence of S. globulus in the Lake Superior sample, it was not found among the specimens sequenced from Wisconsin or Minnesota.

Sphaeridiotrema globulus and Sphaeridiotrema pseudoglobulus (Digenea): Species Differentiation Based on mtDNA (Barcode) and Partial LSUrDNA Sequences

USGS Publications Warehouse

Bergmame, L.; Huffman, J.; Cole, R.; Dayanandan, S.; Tkach, V.; McLaughlin, J.D.

2011-01-01

Flukes belonging to Sphaeridiotrema are important parasites of waterfowl, and 2 morphologically similar species Sphaeridiotrema globulus and Sphaeridiotrema pseudoglobulus, have been implicated in waterfowl mortality in North America. Cytochrome oxidase I (barcode region) and partial LSU-rDNA sequences from specimens of S. globulus and S. pseudoglobulus, obtained from naturally and experimentally infected hosts from New Jersey and Quebec, respectively, confirmed that these species were distinct. Barcode sequences of the 2 species differed at 92 of 590 nucleotide positions (15.6%) and the translated sequences differed by 13 amino acid residues. Partial LSU-rDNA sequences differed at 29 of 1,208 nucleotide positions (2.4%). Additional barcode sequences from specimens collected from waterfowl in Wisconsin and Minnesota and morphometric data obtained from specimens acquired along the north shore of Lake Superior revealed the presence of S. pseudoglobulus in these areas. Although morphometric data suggested the presence of S. globulus in the Lake Superior sample, it was not found among the specimens sequenced from Wisconsin or Minnesota. ?? 2011 American Society of Parasitologists.

[Peripheral refraction and retinal contour in congenital and acquired high myopia].

PubMed

Tarutta, E P; Markosyan, G A; Milash, S V

to perform a comparative study of peripheral refraction and retinal contour in patients with congenital versus acquired high myopia. A total of 30 patients (60 eyes) with high myopia aged 8 to 18 years (11.2±0.32 years on average) were examined. The patients were divided into 2 groups. Group 1 consisted of 21 patients (42 eyes) with acquired myopia of -6.0 to -10.25 diopters (-7.55±0.17 diopters on average), group 2 - of 9 patients (18 eyes) with congenital myopia of -8.75 to -28.75 diopters (-16.39±1.24 diopters on average). Using the Grand Seiko WR-5100K binocular open-field autoref/keratometer (Japan), relative peripheral refraction was assessed with account to relative peripheral eye length measured by the IOL Master partial coherent interferometer ('Carl Zeiss', Germany) at 15° and 30° nasally and temporally from the foveal center along the horizontal meridian. In acquired myopia, relative peripheral refraction and relative peripheral eye length readings evidenced the formation of peripheral hyperopic defocus in all examined zones. Congenital high myopia cases were notable for myopic defocus at 15° of the nasal retina (N15 zone): -0.67±0.33 diopters against the eye length change of -0.33±0.13 mm. The research helped identify retinal contour changes characteristic of congenital myopia and indicative of posterior pole irregularity.

Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure

PubMed Central

Mohan, Joanne; Hopkins, John; Mabbott, Neil A

2005-01-01

The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node. PMID:16108824

Development of a Dedicated Radiotherapy Unit with Real-Time Image Guidance and Motion Management for Accelerated Partial Breast Irradiation

DTIC Science & Technology

2012-08-01

respiratory motions using 4D tagged magnetic resonance imaging ( MRI ) data and 4D high-resolution respiratory-gated CT data respectively. Both...dimensional segmented human anatomy. Medical Physics, 1994. 21(2): p. 299-302. 6. Zubal, I.G., et al. High resolution, MRI -based, segmented...the beam direction. T2-weighted images were acquired after 24 hours with a 3T- MRI scanner using a turbo spin-echo sequence. Imaging parameters were

Optical solitons, nonlinear self-adjointness and conservation laws for the cubic nonlinear Shrödinger's equation with repulsive delta potential

NASA Astrophysics Data System (ADS)

Baleanu, Dumitru; Inc, Mustafa; Aliyu, Aliyu Isa; Yusuf, Abdullahi

2017-11-01

In this paper, the complex envelope function ansatz method is used to acquire the optical solitons to the cubic nonlinear Shrödinger's equation with repulsive delta potential (δ-NLSE). The method reveals dark and bright optical solitons. The necessary constraint conditions which guarantee the existence of the solitons are also presented. We studied the δ-NLSE by analyzing a system of partial differential equations (PDEs) obtained by decomposing the equation into real and imaginary components. We derive the Lie point symmetry generators of the system and prove that the system is nonlinearly self-adjoint with an explicit form of a differential substitution satisfying the nonlinear self-adjoint condition. Then we use these facts to establish a set of conserved vectors for the system using the general Cls theorem presented by Ibragimov. Some interesting figures for the acquired solutions are also presented.

Ships and Maritime Targets Observation Campaigns Using Available C- and X-Band SAR Satellite

NASA Astrophysics Data System (ADS)

Velotto, Domenico; Bentes, Carlos; Lehner, Susanne

2015-04-01

Obviously, radar resolution and swath width are two very important factors when it comes to synthetic aperture radar (SAR) maritime targets detections. The dilemma of using single polarization SAR imagery with higher resolution and coverage or quad- (or dual- polarimetric) imagery with its richness of information, is still unsolved when it comes to this application.In the framework of ESA project MARISS and EU project DOLPHIN, in situ campaigns aimed at solving this dilemma have been carried out. Single and multi- polarimetric SAR data acquired by TerraSAR-X, RADARSAT-2 and COSMO-SkyMed have been acquired with close time gaps and partial coverage overlap. In this way several moving and non-moving maritime targets have been imaged with different polarization, geometry and working frequency. Available ground truth reports provided by Automatic Identification System (AIS) data, nautical chart and wind farm location are used to validate the different types of maritime targets.

Acquired perforating dermatosis in a patient with Poland syndrome.

PubMed

Fistarol, Susanna K; Itin, Peter H

2003-01-01

Acquired perforating dermatosis (APD) is characterized by umbilicated 1- to 10-mm-measuring papulonodules with a central adherent oystershell-like keratotic plug, typically on the dorsa of the hands, forearms and over the knees. APD is associated with systemic diseases, especially diabetes mellitus and/or renal failure. Histologically the lesions show transepidermal elimination of altered dermal components into a cup-shaped epidermal depression. We present a 69-year-old man with coexisting APD and Poland syndrome (PS), an association not yet described. PS (OMIM 173800) is a rare congenital anomaly consisting of unilateral partial or total absence of the greater pectoralis muscle and ipsilateral symbrachydactyly. Most cases of PS are sporadic as it was in our case. Our patient had, in addition, an untreated diabetic condition, hyperuricaemia, dilated cardiomyopathy and a very recent pulmonary embolism. He responded to therapy with allopurinol. Copyright 2003 S. Karger AG, Basel

Automatic mapping of strip mine operations from spacecraft data. [Ohio

NASA Technical Reports Server (NTRS)

Rogers, R. H. (Principal Investigator); Reed, L. E.; Pettyjohn, W. A.

1974-01-01

The author has identified the following significant results. Computer techniques were applied to process ERTS tapes acquired over coal mining operations in southeastern Ohio on 21 August 1972 and 3 September 1973. ERTS products obtained included geometrically-correct map overlays, at scales from 1:24,000 to 1:250,000, showing stripped earth, partially reclaimed earth, water, and natural vegetation. Computer-generated tables listing the area covered by each land-water category in square kilometers were also produced. By comparing these mapping products, the study demonstrates the capability of ERTS to monitor changes in the extent of stripping and reclamation. NASA C-130 photography acquired on 7 September 1973 when compared with the ERTS products generated from the 3 September 1973 tape established the categorization accuracy to be better than 90%. It is estimated that the stripping and reclamation maps and data were produced from the ERTS CCTs at a tenth of the cost of conventional techniques.

Spectroscopic approach for dynamic bioanalyte tracking with minimal concentration information

NASA Astrophysics Data System (ADS)

Spegazzini, Nicolas; Barman, Ishan; Dingari, Narahara Chari; Pandey, Rishikesh; Soares, Jaqueline S.; Ozaki, Yukihiro; Dasari, Ramachandra Rao

2014-11-01

Vibrational spectroscopy has emerged as a promising tool for non-invasive, multiplexed measurement of blood constituents - an outstanding problem in biophotonics. Here, we propose a novel analytical framework that enables spectroscopy-based longitudinal tracking of chemical concentration without necessitating extensive a priori concentration information. The principal idea is to employ a concentration space transformation acquired from the spectral information, where these estimates are used together with the concentration profiles generated from the system kinetic model. Using blood glucose monitoring by Raman spectroscopy as an illustrative example, we demonstrate the efficacy of the proposed approach as compared to conventional calibration methods. Specifically, our approach exhibits a 35% reduction in error over partial least squares regression when applied to a dataset acquired from human subjects undergoing glucose tolerance tests. This method offers a new route at screening gestational diabetes and opens doors for continuous process monitoring without sample perturbation at intermediate time points.

Southern Quebec in Late Winter

NASA Technical Reports Server (NTRS)

2002-01-01

These images of Canada's Quebec province were acquired by the Multi-angle Imaging SpectroRadiometer on March 4, 2001. The region's forests are a mixture of coniferous and hardwood trees, and 'sugar-shack' festivities are held at this time of year to celebrate the beginning of maple syrup production. The large river visible in the images is the northeast-flowing St. Lawrence. The city of Montreal is located near the lower left corner, and Quebec City, at the upper right, is near the mouth of the partially ice-covered St. Lawrence Seaway.

Both spectral and angular information are retrieved for every scene observed by MISR. The left-hand image was acquired by the instrument's vertical-viewing (nadir) camera, and is a false-color spectral composite from the near-infrared, red, and blue bands. The right-hand image is a false-color angular composite using red band data from the 60-degree backward-viewing, nadir, and 60-degree forward-viewing cameras. In each case, the individual channels of data are displayed as red, green, and blue, respectively.

Much of the ground remains covered or partially covered with snow. Vegetation appears red in the left-hand image because of its high near-infrared brightness. In the multi-angle composite, vegetated areas appear in shades of green because they are brighter at nadir, possibly as a result of an underlying blanket of snow which is more visible from this direction. Enhanced forward scatter from the smooth water surface results in bluer hues, whereas urban areas look somewhat orange, possibly due to the effect of vertical structures which preferentially backscatter sunlight.

The data were acquired during Terra orbit 6441, and cover an area measuring 275 kilometers x 310 kilometers.

MISR was built and is managed by NASA's Jet Propulsion Laboratory, Pasadena, CA, for NASA's Office of Earth Science, Washington, DC. The Terra satellite is managed by NASA's Goddard Space Flight Center, Greenbelt, MD. JPL is a division of the California Institute of Technology.

Dual-modality imaging of function and physiology

NASA Astrophysics Data System (ADS)

Hasegawa, Bruce H.; Iwata, Koji; Wong, Kenneth H.; Wu, Max C.; Da Silva, Angela; Tang, Hamilton R.; Barber, William C.; Hwang, Andrew B.; Sakdinawat, Anne E.

2002-04-01

Dual-modality imaging is a technique where computed tomography or magnetic resonance imaging is combined with positron emission tomography or single-photon computed tomography to acquire structural and functional images with an integrated system. The data are acquired during a single procedure with the patient on a table viewed by both detectors to facilitate correlation between the structural and function images. The resulting data can be useful for localization for more specific diagnosis of disease. In addition, the anatomical information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can be used to improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems also are being developed for biological research that involves small animals. The small-animal dual-modality systems offer advantages for measurements that currently are performed invasively using autoradiography and tissue sampling. By acquiring the required data noninvasively, dual-modality imaging has the potential to allow serial studies in a single animal, to perform measurements with fewer animals, and to improve the statistical quality of the data.

Reconstruction of acquired sub-total ear defects with autologous costal cartilage.

PubMed

Harris, P A; Ladhani, K; Das-Gupta, R; Gault, D T

1999-06-01

Acquired sub-total ear defects are common and challenging to reconstruct. We report the use of an autologous costal cartilage framework to reconstruct sub-total defects involving all anatomical regions of the ear. Twenty-eight partially damaged ears in 27 patients were reconstructed with this technique. The defects resulted from bites (14), road traffic accidents (five), burns (four), iatrogenic causes (four) and chondritis following minor trauma (one). Computerised image analysis revealed a median of 31% (range 13-72%) ear loss. An autologous costal cartilage framework was fashioned in all cases. If adequate local skin was available, this was draped over the framework, but in nine cases preliminary tissue expansion was used and in a further three cases with significant scarring, the framework was covered with a temporoparietal fascial flap. Clinical assessment after ear reconstruction was undertaken, scoring for symmetry, the helical rim, the antihelical fold, the lobe position and a 'natural look' to produce a four-point scale; 11 were excellent, 12 were good, two were fair and three were poor. Our experience suggests that formal delayed reconstruction with autologous costal cartilage is to be recommended when managing acquired, sub-total ear deformity.

Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib.

PubMed

Ignatius Ou, Sai-Hong; Azada, Michele; Hsiang, David J; Herman, June M; Kain, Tatiana S; Siwak-Tapp, Christina; Casey, Cameron; He, Jie; Ali, Siraj M; Klempner, Samuel J; Miller, Vincent A

2014-04-01

Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment. Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib. In a second case, we identified a secondary acquired ALK G1202R, which also confers resistance to alectinib (CH5424802/RO5424802), a second-generation ALK inhibitor that can inhibit ALK gatekeeper L1196M mutation in vitro. ALK G1202R is located at the solvent front of the ALK kinase domain and exhibits a high level of resistance to all other ALK inhibitors currently in clinical development in vitro. Comprehensive genomic profiling of resistant tumor is increasingly important in tailoring treatment decisions after disease progression on crizotinib in ALK+ NSCLC given the promise of second-generation ALK inhibitors and other therapeutic strategies.

A new integrated dual time-point amyloid PET/MRI data analysis method.

PubMed

Cecchin, Diego; Barthel, Henryk; Poggiali, Davide; Cagnin, Annachiara; Tiepolt, Solveig; Zucchetta, Pietro; Turco, Paolo; Gallo, Paolo; Frigo, Anna Chiara; Sabri, Osama; Bui, Franco

2017-11-01

In the initial evaluation of patients with suspected dementia and Alzheimer's disease, there is no consensus on how to perform semiquantification of amyloid in such a way that it: (1) facilitates visual qualitative interpretation, (2) takes the kinetic behaviour of the tracer into consideration particularly with regard to at least partially correcting for blood flow dependence, (3) analyses the amyloid load based on accurate parcellation of cortical and subcortical areas, (4) includes partial volume effect correction (PVEC), (5) includes MRI-derived topographical indexes, (6) enables application to PET/MRI images and PET/CT images with separately acquired MR images, and (7) allows automation. A method with all of these characteristics was retrospectively tested in 86 subjects who underwent amyloid ( 18 F-florbetaben) PET/MRI in a clinical setting (using images acquired 90-110 min after injection, 53 were classified visually as amyloid-negative and 33 as amyloid-positive). Early images after tracer administration were acquired between 0 and 10 min after injection, and later images were acquired between 90 and 110 min after injection. PVEC of the PET data was carried out using the geometric transfer matrix method. Parametric images and some regional output parameters, including two innovative "dual time-point" indexes, were obtained. Subjects classified visually as amyloid-positive showed a sparse tracer uptake in the primary sensory, motor and visual areas in accordance with the isocortical stage of the topographic distribution of the amyloid plaque (Braak stages V/VI). In patients classified visually as amyloid-negative, the method revealed detectable levels of tracer uptake in the basal portions of the frontal and temporal lobes, areas that are known to be sites of early deposition of amyloid plaques that probably represented early accumulation (Braak stage A) that is typical of normal ageing. There was a strong correlation between age and the indexes of the new dual time-point amyloid imaging method in amyloid-negative patients. The method can be considered a valuable tool in both routine clinical practice and in the research setting as it will standardize data regarding amyloid deposition. It could potentially also be used to identify early amyloid plaque deposition in younger subjects in whom treatment could theoretically be more effective.

Dictionary Learning for Data Recovery in Positron Emission Tomography

PubMed Central

Valiollahzadeh, SeyyedMajid; Clark, John W.; Mawlawi, Osama

2015-01-01

Compressed sensing (CS) aims to recover images from fewer measurements than that governed by the Nyquist sampling theorem. Most CS methods use analytical predefined sparsifying domains such as Total variation (TV), wavelets, curvelets, and finite transforms to perform this task. In this study, we evaluated the use of dictionary learning (DL) as a sparsifying domain to reconstruct PET images from partially sampled data, and compared the results to the partially and fully sampled image (baseline). A CS model based on learning an adaptive dictionary over image patches was developed to recover missing observations in PET data acquisition. The recovery was done iteratively in two steps: a dictionary learning step and an image reconstruction step. Two experiments were performed to evaluate the proposed CS recovery algorithm: an IEC phantom study and five patient studies. In each case, 11% of the detectors of a GE PET/CT system were removed and the acquired sinogram data were recovered using the proposed DL algorithm. The recovered images (DL) as well as the partially sampled images (with detector gaps) for both experiments were then compared to the baseline. Comparisons were done by calculating RMSE, contrast recovery and SNR in ROIs drawn in the background, and spheres of the phantom as well as patient lesions. For the phantom experiment, the RMSE for the DL recovered images were 5.8% when compared with the baseline images while it was 17.5% for the partially sampled images. In the patients’ studies, RMSE for the DL recovered images were 3.8%, while it was 11.3% for the partially sampled images. Our proposed CS with DL is a good approach to recover partially sampled PET data. This approach has implications towards reducing scanner cost while maintaining accurate PET image quantification. PMID:26161630

Dictionary learning for data recovery in positron emission tomography

NASA Astrophysics Data System (ADS)

Valiollahzadeh, SeyyedMajid; Clark, John W., Jr.; Mawlawi, Osama

2015-08-01

Compressed sensing (CS) aims to recover images from fewer measurements than that governed by the Nyquist sampling theorem. Most CS methods use analytical predefined sparsifying domains such as total variation, wavelets, curvelets, and finite transforms to perform this task. In this study, we evaluated the use of dictionary learning (DL) as a sparsifying domain to reconstruct PET images from partially sampled data, and compared the results to the partially and fully sampled image (baseline). A CS model based on learning an adaptive dictionary over image patches was developed to recover missing observations in PET data acquisition. The recovery was done iteratively in two steps: a dictionary learning step and an image reconstruction step. Two experiments were performed to evaluate the proposed CS recovery algorithm: an IEC phantom study and five patient studies. In each case, 11% of the detectors of a GE PET/CT system were removed and the acquired sinogram data were recovered using the proposed DL algorithm. The recovered images (DL) as well as the partially sampled images (with detector gaps) for both experiments were then compared to the baseline. Comparisons were done by calculating RMSE, contrast recovery and SNR in ROIs drawn in the background, and spheres of the phantom as well as patient lesions. For the phantom experiment, the RMSE for the DL recovered images were 5.8% when compared with the baseline images while it was 17.5% for the partially sampled images. In the patients’ studies, RMSE for the DL recovered images were 3.8%, while it was 11.3% for the partially sampled images. Our proposed CS with DL is a good approach to recover partially sampled PET data. This approach has implications toward reducing scanner cost while maintaining accurate PET image quantification.

Use of IT platform in determination of efficiency of mining machines

NASA Astrophysics Data System (ADS)

Brodny, Jarosław; Tutak, Magdalena

2018-01-01

Determination of effective use of mining devices has very significant meaning for mining enterprises. High costs of their purchase and tenancy cause that these enterprises tend to the best use of possessed technical potential. However, specifics of mining production causes that this process not always proceeds without interferences. Practical experiences show that determination of objective measure of utilization of machine in mining enterprise is not simple. In the paper a proposition for solution of this problem is presented. For this purpose an IT platform and overall efficiency model OEE were used. This model enables to evaluate the machine in a range of its availability performance and quality of product, and constitutes a quantitative tool of TPM strategy. Adapted to the specificity of mining branch the OEE model together with acquired data from industrial automatic system enabled to determine the partial indicators and overall efficiency of tested machines. Studies were performed for a set of machines directly use in coal exploitation process. They were: longwall-shearer and armoured face conveyor, and beam stage loader. Obtained results clearly indicate that degree of use of machines by mining enterprises are unsatisfactory. Use of IT platforms will significantly facilitate the process of registration, archiving and analytical processing of the acquired data. In the paper there is presented methodology of determination of partial indices and total OEE together with a practical example of its application for investigated machines set. Also IT platform was characterized for its construction, function and application.

Imaging the equilibrium state and magnetization dynamics of partially built hard disk write heads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valkass, R. A. J., E-mail: rajv202@ex.ac.uk; Yu, W.; Shelford, L. R.

Four different designs of partially built hard disk write heads with a yoke comprising four repeats of NiFe (1 nm)/CoFe (50 nm) were studied by both x-ray photoemission electron microscopy (XPEEM) and time-resolved scanning Kerr microscopy (TRSKM). These techniques were used to investigate the static equilibrium domain configuration and the magnetodynamic response across the entire structure, respectively. Simulations and previous TRSKM studies have made proposals for the equilibrium domain configuration of similar structures, but no direct observation of the equilibrium state of the writers has yet been made. In this study, static XPEEM images of the equilibrium state of writer structures weremore » acquired using x-ray magnetic circular dichroism as the contrast mechanism. These images suggest that the crystalline anisotropy dominates the equilibrium state domain configuration, but competition with shape anisotropy ultimately determines the stability of the equilibrium state. Dynamic TRSKM images were acquired from nominally identical devices. These images suggest that a longer confluence region may hinder flux conduction from the yoke into the pole tip: the shorter confluence region exhibits clear flux beaming along the symmetry axis, whereas the longer confluence region causes flux to conduct along one edge of the writer. The observed variations in dynamic response agree well with the differences in the equilibrium magnetization configuration visible in the XPEEM images, confirming that minor variations in the geometric design of the writer structure can have significant effects on the process of flux beaming.« less

Prototype volumetric ultrasound tomography image guidance system for prone stereotactic partial breast irradiation: proof-of-concept

NASA Astrophysics Data System (ADS)

Chiu, Tsuicheng D.; Parsons, David; Zhang, Yue; Hrycushko, Brian; Zhao, Bo; Chopra, Rajiv; Kim, Nathan; Spangler, Ann; Rahimi, Asal; Timmerman, Robert; Jiang, Steve B.; Lu, Weiguo; Gu, Xuejun

2018-03-01

Accurate dose delivery in stereotactic partial breast irradiation (S-PBI) is challenging because of the target position uncertainty caused by breast deformation, the target volume changes caused by lumpectomy cavity shrinkage, and the target delineation uncertainty on simulation computed tomography (CT) images caused by poor soft tissue contrast. We have developed a volumetric ultrasound tomography (UST) image guidance system for prone position S-PBI. The system is composed of a novel 3D printed rotation water tank, a patient-specific resin breast immobilization cup, and a 1D array ultrasound transducer. Coronal 2D US images were acquired in 5° increments over a 360° range, and planes were acquired every 2 mm in elevation. A super-compounding technique was used to reconstruct the image volume. The image quality of UST was evaluated with a BB-1 breast phantom and BioZorb surgical marker, and the results revealed that UST offered better soft tissue contrast than CT and similar image quality to MR. In the evaluated plane, the size and location of five embedded objects were measured and compared to MR, which is considered as the ground truth. Objects’ diameters and the distances between objects in UST differ by approximately 1 to 2 mm from those in MR, which showed that UST offers the image quality required for S-PBI. In future work we will develop a robotic system that will be ultimately implemented in the clinic.

Prototype volumetric ultrasound tomography image guidance system for prone stereotactic partial breast irradiation: proof-of-concept.

PubMed

Chiu, Tsuicheng D; Parsons, David; Zhang, Yue; Hrycushko, Brian; Zhao, Bo; Chopra, Rajiv; Kim, Nathan; Spangler, Ann; Rahimi, Asal; Timmerman, Robert; Jiang, Steve B; Lu, Weiguo; Gu, Xuejun

2018-03-01

Accurate dose delivery in stereotactic partial breast irradiation (S-PBI) is challenging because of the target position uncertainty caused by breast deformation, the target volume changes caused by lumpectomy cavity shrinkage, and the target delineation uncertainty on simulation computed tomography (CT) images caused by poor soft tissue contrast. We have developed a volumetric ultrasound tomography (UST) image guidance system for prone position S-PBI. The system is composed of a novel 3D printed rotation water tank, a patient-specific resin breast immobilization cup, and a 1D array ultrasound transducer. Coronal 2D US images were acquired in 5° increments over a 360° range, and planes were acquired every 2 mm in elevation. A super-compounding technique was used to reconstruct the image volume. The image quality of UST was evaluated with a BB-1 breast phantom and BioZorb surgical marker, and the results revealed that UST offered better soft tissue contrast than CT and similar image quality to MR. In the evaluated plane, the size and location of five embedded objects were measured and compared to MR, which is considered as the ground truth. Objects' diameters and the distances between objects in UST differ by approximately 1 to 2 mm from those in MR, which showed that UST offers the image quality required for S-PBI. In future work we will develop a robotic system that will be ultimately implemented in the clinic.

Hugoniot measurements of double-shocked precompressed dense xenon plasmas

NASA Astrophysics Data System (ADS)

Zheng, J.; Chen, Q. F.; Gu, Y. J.; Chen, Z. Y.

2012-12-01

The current partially ionized plasmas models for xenon show substantial differences since the description of pressure and thermal ionization region becomes a formidable task, prompting the need for an improved understanding of dense xenon plasmas behavior at above 100 GPa. We performed double-shock compression experiments on dense xenon to determine accurately the Hugoniot up to 172 GPa using a time-resolved optical radiation method. The planar strong shock wave was produced using a flyer plate impactor accelerated up to ˜6 km/s with a two-stage light-gas gun. The time-resolved optical radiation histories were acquired by using a multiwavelength channel optical transience radiance pyrometer. Shock velocity was measured and mass velocity was determined by the impedance-matching methods. The experimental equation of state of dense xenon plasmas are compared with the self-consistent fluid variational calculations of dense xenon in the region of partial ionization over a wide range of pressures and temperatures.

Does cultural exposure partially explain the association between personality and political orientation?

PubMed

Xu, Xiaowen; Mar, Raymond A; Peterson, Jordan B

2013-11-01

Differences in political orientation are partly rooted in personality, with liberalism predicted by Openness to Experience and conservatism by Conscientiousness. Since Openness is positively associated with intellectual and creative activities, these may help shape political orientation. We examined whether exposure to cultural activities and historical knowledge mediates the relationship between personality and political orientation. Specifically, we examined the mediational role of print exposure (Study 1), film exposure (Study 2), and knowledge of American history (Study 3). Studies 1 and 2 found that print and film exposure mediated the relationships Openness to Experience and Conscientiousness have with political orientation. In Study 3, knowledge of American history mediated the relationship between Openness and political orientation, but not the association between Conscientiousness and political orientation. Exposure to culture, and a corollary of this exposure in the form of acquiring knowledge, can therefore partially explain the associations between personality and political orientation.

Microstructural Features in Corroded Celtic Iron Age Sword Blades

NASA Astrophysics Data System (ADS)

Ghiara, G.; Piccardo, P.; Campodonico, S.; Carnasciali, M. M.

2014-05-01

Archaeological artefacts made from iron and steel are often of critical importance for archaeometallurgical studies, which aim to understand the process of manufacturing, as the nearly complete alloy mineralization does not allow for any type of metallographic interpretation. In this study, three Iron Age sword blades dated from the second century BC (LaTène B2/D1) found in the archaeological site of Tintignac (Commune de Naves, Corrèze, France), were investigated. A multianalytical approach was employed to acquire a complete range of data from the partially or totally corroded objects. Analyses were carried out with the use of light optical microscopy, micro Raman spectroscopy, and scanning electron microscopy equipped with energy-dispersive x-ray spectroscopy (EDXS). Remnants of metallographic features—ghost microstructure—in the corrosion layers of the blades were observed, allowing for a partial reconstruction of the manufacturing process.

Optimal vaccination and bednet maintenance for the control of malaria in a region with naturally acquired immunity.

PubMed

Prosper, Olivia; Ruktanonchai, Nick; Martcheva, Maia

2014-07-21

Following over two decades of research, the malaria vaccine candidate RTS,S has reached the final stages of vaccine trials, demonstrating an efficacy of roughly 50% in young children. Regions with high malaria prevalence tend to have high levels of naturally acquired immunity (NAI) to severe malaria; NAI is caused by repeated exposure to infectious bites and results in large asymptomatic populations. To address concerns about how these vaccines will perform in regions with existing NAI, we developed a simple malaria model incorporating vaccination and NAI. Typically, if the basic reproduction number (R0) for malaria is greater than unity, the disease will persist; otherwise, the disease will become extinct. However, analysis of this model revealed that NAI, compounded by a subpopulation with only partial protection to malaria, may render vaccination efforts ineffective and potentially detrimental to malaria control, by increasing R0 and increasing the likelihood of malaria persistence even when R0<1. The likelihood of this scenario increases when non-immune infected individuals are treated disproportionately compared with partially immune individuals - a plausible scenario since partially immune individuals are more likely to be asymptomatically infected. Consequently, we argue that active case-detection of asymptomatic infections is a critical component of an effective malaria control program. We then investigated optimal vaccination and bednet control programs under two endemic settings with varying levels of naturally acquired immunity: a typical setting under which prevalence decays when R0<1, and a setting in which subthreshold endemic equilibria exist. A qualitative comparison of the optimal control results under the first setting revealed that the optimal policy differs depending on whether the goal is to reduce total morbidity, or to reduce clinical infections. Furthermore, this comparison dictates that control programs should place less effort in vaccination as the level of NAI in a population, and as disease prevalence, increases. In the second setting, we demonstrated that the optimal policy is able to confer long-term benefits with a 10-year control program by pushing the system into a new state where the disease-free equilibrium becomes the attracting equilibrium. While this result suggests that one can theoretically achieve long-term benefits with a short-term strategy, we illustrate that in this second setting, a small environmental change, or the introduction of new cases via immigration, places the population at high risk for a malaria epidemic. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anarchic Yukawas and top partial compositeness: the flavour of a successful marriage

NASA Astrophysics Data System (ADS)

Cacciapaglia, Giacomo; Cai, Haiying; Flacke, Thomas; Lee, Seung J.; Parolini, Alberto; Serôdio, Hugo

2015-06-01

The top quark can be naturally singled out from other fermions in the Standard Model due to its large mass, of the order of the electroweak scale. We follow this reasoning in models of pseudo Nambu Goldstone Boson composite Higgs, which may derive from an underlying confining dynamics. We consider a new class of flavour models, where the top quark obtains its mass via partial compositeness, while the lighter fermions acquire their masses by a deformation of the dynamics generated at a high flavour scale. One interesting feature of such scenario is that it can avoid all the flavour constraints without the need of flavour symmetries, since the flavour scale can be pushed high enough. We show that both flavour conserving and violating constraints can be satisfied with top partial compositeness without invoking any flavour symmetry for the up-type sector, in the case of the minimal SO(5)/SO(4) coset with top partners in the four-plet and singlet of SO(4). In the down-type sector, some degree of alignment is required if all down-type quarks are elementary. We show that taking the bottom quark partially composite provides a dynamical explanation for the hierarchy causing this alignment. We present explicit realisations of this mechanism which do not require to include additional bottom partner fields. Finally, these conclusions are generalised to scenarios with non-minimal cosets and top partners in larger representations.

Digital tomosynthesis mammography using a parallel maximum-likelihood reconstruction method

NASA Astrophysics Data System (ADS)

Wu, Tao; Zhang, Juemin; Moore, Richard; Rafferty, Elizabeth; Kopans, Daniel; Meleis, Waleed; Kaeli, David

2004-05-01

A parallel reconstruction method, based on an iterative maximum likelihood (ML) algorithm, is developed to provide fast reconstruction for digital tomosynthesis mammography. Tomosynthesis mammography acquires 11 low-dose projections of a breast by moving an x-ray tube over a 50° angular range. In parallel reconstruction, each projection is divided into multiple segments along the chest-to-nipple direction. Using the 11 projections, segments located at the same distance from the chest wall are combined to compute a partial reconstruction of the total breast volume. The shape of the partial reconstruction forms a thin slab, angled toward the x-ray source at a projection angle 0°. The reconstruction of the total breast volume is obtained by merging the partial reconstructions. The overlap region between neighboring partial reconstructions and neighboring projection segments is utilized to compensate for the incomplete data at the boundary locations present in the partial reconstructions. A serial execution of the reconstruction is compared to a parallel implementation, using clinical data. The serial code was run on a PC with a single PentiumIV 2.2GHz CPU. The parallel implementation was developed using MPI and run on a 64-node Linux cluster using 800MHz Itanium CPUs. The serial reconstruction for a medium-sized breast (5cm thickness, 11cm chest-to-nipple distance) takes 115 minutes, while a parallel implementation takes only 3.5 minutes. The reconstruction time for a larger breast using a serial implementation takes 187 minutes, while a parallel implementation takes 6.5 minutes. No significant differences were observed between the reconstructions produced by the serial and parallel implementations.

Changes in the Tinnitus Handicap Questionnaire After Cochlear Implantation

PubMed Central

Pan, Tao; Tyler, Richard S.; Ji, Haihong; Coelho, Claudia; Gehringer, Anne K.; Gogel, Stephanie A.

2010-01-01

Purpose To determine (a) changes in the Tinnitus Handicap Questionnaire (THQ) for patients using cochlear implants, (b) differences between patients who receive total or partial relief, and (c) identifiable characteristics of those who report tinnitus after implantation. Method Pre- and postoperatively, 244 adults were administered the THQ when they reported tinnitus. Results Of the 153 patients who had tinnitus preoperatively, 94 (61%) patients reported total suppression and 59 (39%) reported a partial reduction. In 91 patients who did not have tinnitus before implantation, 11 (12%) reported tinnitus postimplantation. The THQ score decreased from 41% preimplant to 30% postimplant. The largest reductions involved social handicap and hearing. Patients with a more severe hearing loss might be more likely to experience an exacerbation of their tinnitus. We were not able to clearly identify differences between patients who received total or partial relief and the characteristics of patients who reported tinnitus after implantation. Those who acquired tinnitus had the shortest duration hearing loss (5.6 years) and were the oldest (63 years). The average THQ score of patients getting tinnitus was 29%. Conclusions Most tinnitus patients benefit from receiving a cochlear implant. PMID:19949236

The Search for Exotic Mesons in gamma p -> pi+pi+pi-n with CLAS at Jefferson Lab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craig Bookwalter

2011-12-01

The {pi}{sub 1}(1600), a J{sup PC} = 1{sup {-+}} exotic meson has been observed by experiments using pion beams. Theorists predict that photon beams could produce gluonic hybrid mesons, of which the {pi}{sub 1}(1600) is a candidate, at enhanced levels relative to pion beams. The g12 rungroup at Jefferson Lab's CEBAF Large Acceptance Spectrometer (CLAS) has recently acquired a large photoproduction dataset, using a liquid hydrogen target and tagged photons from a 5.71 GeV electron beam. A partial-wave analysis of 502K {gamma}p {yields} {pi}{sup +}{pi}{sup +}{pi}{sup -}n events selected from the g12 dataset has been performed, and preliminary fit resultsmore » show strong evidence for well-known states such as the a{sub 1}(1260), a{sub 2}(1320), and {pi}{sub 2}(1670). However, we observe no evidence for the production of the {pi}{sub 1}(1600) in either the partial-wave intensities or the relative complex phase between the 1{sup {-+}} and the 2{sup {-+}} (corresponding to the {pi}{sub 2}) partial waves.« less

Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study.

PubMed

Luo, Cheng; Qiu, Chuan; Guo, Zhiwei; Fang, Jiajia; Li, Qifu; Lei, Xu; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Zhou, Dong; Yao, Dezhong

2011-01-01

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.

Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

PubMed

Rocha, Nuno; Bulger, David A; Frontini, Andrea; Titheradge, Hannah; Gribsholt, Sigrid Bjerge; Knox, Rachel; Page, Matthew; Harris, Julie; Payne, Felicity; Adams, Claire; Sleigh, Alison; Crawford, John; Gjesing, Anette Prior; Bork-Jensen, Jette; Pedersen, Oluf; Barroso, Inês; Hansen, Torben; Cox, Helen; Reilly, Mary; Rossor, Alex; Brown, Rebecca J; Taylor, Simeon I; McHale, Duncan; Armstrong, Martin; Oral, Elif A; Saudek, Vladimir; O'Rahilly, Stephen; Maher, Eamonn R; Richelsen, Bjørn; Savage, David B; Semple, Robert K

2017-04-19

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies.

A TALEN genome editing system to generate human stem cell-based disease models

PubMed Central

Ding, Qiurong; Lee, Youn-Kyoung; Schaefer, Esperance A. K.; Peters, Derek T.; Veres, Adrian; Kim, Kevin; Kuperwasser, Nicolas; Motola, Daniel L.; Meissner, Torsten B.; Hendriks, William T.; Trevisan, Marta; Gupta, Rajat M.; Moisan, Annie; Banks, Eric; Friesen, Max; Schinzel, Robert T.; Xia, Fang; Tang, Alexander; Xia, Yulei; Figueroa, Emmanuel; Wann, Amy; Ahfeldt, Tim; Daheron, Laurence; Zhang, Feng; Rubin, Lee L.; Peng, Lee F.; Chung, Raymond T.; Musunuru, Kiran; Cowan, Chad A.

2012-01-01

SUMMARY Transcription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter of which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease—dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor neuron death, and hepatitis C infection. We find little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease. PMID:23246482

The nuclear lamina in health and disease

PubMed Central

Dobrzynska, Agnieszka; Gonzalo, Susana; Shanahan, Catherine; Askjaer, Peter

2016-01-01

ABSTRACT The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases. PMID:27158763

Nuclear lamina remodelling and its implications for human disease.

PubMed

Chojnowski, Alexandre; Ong, Peh Fern; Dreesen, Oliver

2015-06-01

The intermediate filament A- and B-type lamins are key architectural components of the nuclear lamina, a proteinaceous meshwork that lies underneath the inner nuclear membrane. In the past decade, many different monogenic human diseases have been linked to mutations in various components of the nuclear lamina. Mutations in LMNA (encoding lamin A and C) cause a variety of human diseases, collectively called laminopathies. These include cardiomyopathies, muscular dystrophies, lipodystrophies and progeroid syndromes. In addition, elevated levels of lamin B1, attributable to genomic duplications of the LMNB1 locus, cause adult-onset autosomal dominant leukodystrophy. The molecular mechanism(s) enabling the mutations and perturbations of the nuclear lamina to give rise to such a wide variety of diseases that affect various tissues remains unclear. The composition of the nuclear lamina changes dynamically during development, between cell types and even within the same cell during differentiation and ageing. Here, we discuss the functional and cellular aspects of lamina remodelling and their implications for the tissue-specific nature of laminopathies.

The Potential of Leptin for Treating Diabetes and Its Mechanism of Action

PubMed Central

Coppari, Roberto; Bjørbæk, Christian

2014-01-01

Following the discovery of leptin in 1994, major research efforts have brought us much closer to a fuller understanding of the cellular and molecular mechanisms underlying the biological effects of the hormone. Interestingly, leptin exerts potent anti-diabetic actions that are independent of its effects on body weight and food intake. In particular, leptin can correct diabetes in animal models of either diabetes mellitus type 1 (T1DM) or type 2 (T2DM). In addition, long-term leptin-replacement therapy is well tolerated and dramatically improves glycemic control, insulin sensitivity, and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. Together, these results have spurred enthusiasm for the use of leptin therapy to treat humans suffering from diabetes mellitus. Here, we review current understandings of these glucoregulatory functions of leptin, with particular emphasis on its central mechanisms of action, lessons from clinical studies and discuss possible therapeutic applications of leptin in the treatment of T1DM and T2DM. PMID:22935803

Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

PubMed Central

da Cunha, Joel; Maselli, Luciana Morganti Ferreira; Stern, Ana Carolina Bassi; Spada, Celso; Bydlowski, Sérgio Paulo

2015-01-01

For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results. PMID:25964872

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

PubMed Central

Schleinitz, Dorit

2015-01-01

Adipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the “protective” allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed. PMID:26859657

The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets.

PubMed

Romanauska, Anete; Köhler, Alwin

2018-06-13

The inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. Here, we show that the INM is an adaptable membrane territory capable of lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets from the INM and is characterized by lipid exchange through Seipin-dependent membrane bridges. We identify the genetic circuit for nuclear lipid droplet synthesis and a role of these organelles in regulating this circuit by sequestration of a transcription factor. Our findings suggest a link between INM metabolism and genome regulation and have potential relevance for human lipodystrophy. Copyright © 2018 Elsevier Inc. All rights reserved.

A geometric level set model for ultrasounds analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarti, A.; Malladi, R.

We propose a partial differential equation (PDE) for filtering and segmentation of echocardiographic images based on a geometric-driven scheme. The method allows edge-preserving image smoothing and a semi-automatic segmentation of the heart chambers, that regularizes the shapes and improves edge fidelity especially in presence of distinct gaps in the edge map as is common in ultrasound imagery. A numerical scheme for solving the proposed PDE is borrowed from level set methods. Results on human in vivo acquired 2D, 2D+time,3D, 3D+time echocardiographic images are shown.

Isolation of Campylobacter fetus subsp. jejuni from migratory waterfowl.

PubMed Central

Luechtefeld, N A; Blaser, M J; Reller, L B; Wang, W L

1980-01-01

Since the sources from which humans acquire Campylobacter enteritis are only partially known, we studied the frequency of carriage of Campylobacter fetus subsp. jejuni in migratory waterfowl. Cecal contents of various species of wild ducks were cultured on selective media that contained antibiotics to inhibit normal flora. Thirty-five percent of the 445 ducks cultured harbored C. fetus subsp. jejuni. Migratory waterfowl are yet another reservoir for this enteric pathogen and may be of public health importance for humans in the contamination of water or when used as food. PMID:7217334

Tsugaru Iwaki Skyline, Japan

NASA Image and Video Library

2018-05-03

The Tsugaru Iwaki Skyline is a toll road in northern Japan, which partially ascends Mount Iwaki stratovolcano, and is notable for its steep gradient and 69 hairpin turns. The road ascends 806 meters over an average gradient of 8.66%, with some sections going up to 10%. The Tsugaru Iwaki Skyline has been considered one of the most dangerous mountain roads in the world. (Wikipedia) The image was acquired May 26, 2015, and is located at 40.6 degrees north, 140.3 degrees east. https://photojournal.jpl.nasa.gov/catalog/PIA22385

Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.

PubMed

Zhou, Libin; Chen, Tingting; Li, Guoxi; Wu, Chaoming; Wang, Conghui; Li, Lin; Sha, Sha; Chen, Lei; Liu, George; Chen, Ling

2016-01-27

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin deficiency causes deficits in spatial memory and hippocampal LTP induction. Neuronal seipin deficiency selectively suppresses AMPA receptor expression, ERK-CREB phosphorylation with the decline of PPARγ. The PPARγ agonist rosiglitazone can ameliorate spatial cognitive deficits and rescue the LTP induction in seipin knock-out mice by restoring AMPA receptor expression and ERK-CREB activities. Copyright © 2016 the authors 0270-6474/16/361242-12$15.00/0.

Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL).

PubMed

Elouej, Sahar; Beleza-Meireles, Ana; Caswell, Richard; Colclough, Kevin; Ellard, Sian; Desvignes, Jean Pierre; Béroud, Christophe; Lévy, Nicolas; Mohammed, Shehla; De Sandre-Giovannoli, Annachiara

2017-06-01

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 patients with MDPL have been reported in the literature and among them 14 patients have been characterized at the molecular level. Twelve unrelated patients carried a recurrent in-frame deletion of a single codon (p.Ser605del) and two other patients carried a novel heterozygous mutation in exon 13 (p.Arg507Cys). Additionally and interestingly, germline mutations of the same gene have been involved in familial polyposis and colorectal cancer (CRC) predisposition. We describe a male and a female patient with MDPL respectively affected with mild and severe phenotypes. Both of them showed mandibular hypoplasia, a beaked nose with bird-like facies, prominent eyes, a small mouth, growth retardation, muscle and skin atrophy, but the female patient showed such a severe and early phenotype that a first working diagnosis of Hutchinson-Gilford Progeria was made. The exploration was performed by direct sequencing of POLD1 gene exon 15 in the male patient with a classical MDPL phenotype and by whole exome sequencing in the female patient and her unaffected parents. Exome sequencing identified in the latter patient a de novo heterozygous undescribed mutation in the POLD1 gene (NM_002691.3: c.3209T>A), predicted to cause the missense change p.Ile1070Asn in the ZnF2 (Zinc Finger 2) domain of the protein. This mutation was not reported in the 1000 Genome Project, dbSNP and Exome sequencing databases. Furthermore, the Isoleucine1070 residue of POLD1 is highly conserved among various species, suggesting that this substitution may cause a major impairment of POLD1 activity. For the second patient, affected with a typical MDPL phenotype, direct sequencing of POLD1 exon 15 revealed the recurrent in-frame deletion (c.1812_1814del, p.S605del). Our work highlights that mutations in different POLD1 domains can lead to phenotypic variability, ranging from dominantly inherited cancer predisposition syndromes, to mild MDPL phenotypes without lifespan reduction, to very severe MDPL syndromes with major premature aging features. These results also suggest that POLD1 gene testing should be considered in patients presenting with severe progeroid features. Copyright © 2017 Elsevier Inc. All rights reserved.

A Blended Learning Experience for Teaching Microbiology

PubMed Central

Sancho, Pilar; Corral, Ricardo; Rivas, Teresa; González, María Jesús; Chordi, Andrés

2006-01-01

Objectives To create a virtual laboratory system in which experimental science students could learn required skills and competencies while overcoming such challenges as time limitations, high cost of resources, and lack of feedback often encountered in a traditional laboratory setting. Design A blended learning experience that combines traditional practices and e-learning was implemented to teach microbiological methods to pharmacy students. Virtual laboratory modules were used to acquire nonmanual skills such as visual and mental skills for data reading, calculations, interpretation of the results, deployment of an analytical protocol, and reporting results. Assesment Learning achievement was evaluated by questions about microbiology case-based problems. Students' perceptions were obtained by assessment questionnaire. Conclusion By combining different learning scenarios, the acquisition of the necessary but otherwise unreachable competences was achieved. Students achieved similar grades in the modules whose initiation was in the virtual laboratory to the grades they achieved with the modules whose complete or partial initiation took place in the laboratory. The knowledge acquired was satisfactory and the participants valued the experience. PMID:17149449

The acquired preparedness risk model applied to smoking in 5th grade children.

PubMed

Combs, Jessica L; Spillane, Nichea S; Caudill, Leann; Stark, Brittany; Smith, Gregory T

2012-03-01

The very early onset of smoking predicts numerous health problems. The authors conducted the first test of one risk model for elementary school age smoking, known as the acquired preparedness (AP) model of risk, in a cross-sectional sample of 309 5th grade children. The model posits that (a) impulsivity-related personality traits contribute to risk for a variety of risky, maladaptive behaviors; (b) smoking expectancies confer risk only for smoking; and (c) the personality traits contribute to the formation of high risk expectancies for reinforcement from smoking, which in turn increases the likelihood of early onset smoking. The model was supported: the high-risk personality traits distinguished children engaging in any risky, maladaptive behavior from other children, and the smoking expectancies differentiated smokers from all other children. The relationship between personality tendencies to act rashly when experiencing intense positive or negative emotions and smoker status was partially mediated by expectancies for reinforcement from smoking. This model should be investigated longitudinally. Copyright © 2011. Published by Elsevier Ltd.

Historical record of Landsat global coverage

USGS Publications Warehouse

Goward, Samuel; Arvidson, Terry; Williams, Darrel; Faundeen, John; Irons, James; Franks, Shannon

2006-01-01

The long-term, 34+ year record of global Landsat remote sensing data is a critical resource to study the Earth system and human impacts on this system. The National Satellite Land Remote Sensing Data Archive (NSLRSDA) is charged by public law to: “maintain a permanent, comprehensive Government archive of global Landsat and other land remote sensing data for long-term monitoring and study of the changing global environment” (U.S. Congress, 1992). The advisory committee for NSLRSDA requested a detailed analysis of observation coverage within the U.S. Landsat holdings, as well as that acquired and held by International Cooperator (IC) stations. Our analyses, to date, have found gaps of varying magnitude in U.S. holdings of Landsat global coverage data, which appear to reflect technical or administrative variations in mission operations. In many cases it may be possible to partially fill these gaps in U.S. holdings through observations that were acquired and are now being held at International Cooperator stations.

Development and transfer of vocabulary knowledge in Spanish-speaking language minority preschool children.

PubMed

Goodrich, J Marc; Lonigan, Christopher J; Kleuver, Cherie G; Farver, Joann M

2016-09-01

In this study we evaluated the predictive validity of conceptual scoring. Two independent samples of Spanish-speaking language minority preschoolers (Sample 1: N = 96, mean age = 54·51 months, 54·3% male; Sample 2: N = 116, mean age = 60·70 months, 56·0% male) completed measures of receptive, expressive, and definitional vocabulary in their first (L1) and second (L2) languages at two time points approximately 9-12 months apart. We examined whether unique L1 and L2 vocabulary at time 1 predicted later L2 and L1 vocabulary, respectively. Results indicated that unique L1 vocabulary did not predict later L2 vocabulary after controlling for initial L2 vocabulary. An identical pattern of results emerged for L1 vocabulary outcomes. We also examined whether children acquired translational equivalents for words known in one language but not the other. Results indicated that children acquired translational equivalents, providing partial support for the transfer of vocabulary knowledge across languages.

Galectin-8 induces partial epithelial–mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin–Darby canine kidney cells

PubMed Central

Oyanadel, Claudia; Holmes, Christopher; Pardo, Evelyn; Retamal, Claudio; Shaughnessy, Ronan; Smith, Patricio; Cortés, Priscilla; Bravo-Zehnder, Marcela; Metz, Claudia; Feuerhake, Teo; Romero, Diego; Roa, Juan Carlos; Montecinos, Viviana; Soza, Andrea; González, Alfonso

2018-01-01

Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial–mesenchymal-transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective β1-integrins involved in EMT and is overexpressed by certain carcinomas. Here we show that Gal-8 overexpression or exogenous addition promotes proliferation, migration, and invasion in nontumoral Madin–Darby canine kidney (MDCK) cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the epidermal growth factor receptor (EGFR), likely triggered by α5β1integrin binding. Under subconfluent conditions, Gal-8–overexpressing MDCK cells (MDCK-Gal-8H) display hallmarks of EMT, including decreased E-cadherin and up-regulated expression of vimentin, fibronectin, and Snail, as well as increased β-catenin activity. Changes related to migration/invasion included higher expression of α5β1 integrin, extracellular matrix-degrading MMP13 and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) protease systems. Gal-8–stimulated FAK/EGFR pathway leads to proteasome overactivity characteristic of cancer cells. Yet MDCK-Gal-8H cells still develop apical/basolateral polarity reverting EMT markers and proteasome activity under confluence. This is due to the opposite segregation of Gal-8 secretion (apical) and β1-integrins distribution (basolateral). Strikingly, MDCK-Gal-8H cells acquired tumorigenic potential, as reflected in anchorage-independent growth in soft agar and tumor generation in immunodeficient NSG mice. Therefore, Gal-8 can promote oncogenic-like transformation of epithelial cells through partial and reversible EMT, accompanied by higher proliferation, migration/invasion, and tumorigenic properties. PMID:29298841

Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

PubMed Central

Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

2016-01-01

Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

Clinical experience with a 3D surface patient setup system for alignment of partial-breast irradiation patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bert, Christoph; Metheany, Katherine G.; Doppke, Karen P.

2006-03-15

Purpose: To assess the utility of surface imaging on patient setup for accelerated partial-breast irradiation (APBI). Methods and Material: A photogrammetry system was used in parallel to APBI setup by laser and portal imaging. Surface data were acquired after laser and port-film setup for 9 patients. Surfaces were analyzed in comparison to a reference surface from the first treatment session by use of rigid transformations. The surface model after laser setup was used in a simulated photogrammetry setup procedure. In addition, breathing data were acquired by surface acquisition at a frame rate of 7 Hz. Results: Mean 3D displacement wasmore » 7.3 mm (SD, 4.4 mm) and 7.6 mm (SD, 4.2 mm) for laser and port film, respectively. Simulated setup with the photogrammetry system yielded mean displacement of 1 mm (SD, 1.2 mm). Distance analysis resulted in mean distances of 3.7 mm (SD, 4.9 mm), 4.3 mm (SD, 5.6 mm), and 1.6 mm (SD, 2.4 mm) for laser, port film, and photogrammetry, respectively. Breathing motion at isocenter was smaller than 3.7 mm, with a mean of 1.9 mm (SD, 1.1 mm). Conclusions: Surface imaging for PBI setup appears promising. Alignment of the 3D breast surface achieved by stereo-photogrammetry shows greater breast topology congruence than when patients are set up by laser or portal imaging. A correlation of breast surface and CTV must be quantitatively established.« less

Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model.

PubMed

Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

2016-09-01

Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction.

Rapid Delivery of Cocaine Facilitates Acquisition of Self-Administration in Rats: An Effect Masked by Paired Stimuli

PubMed Central

Schindler, Charles W.; Cogan, Elizabeth S.; Thorndike, Eric B.; Panlilio, Leigh V.

2011-01-01

In general, faster infusions of cocaine are more likely to support behavior related to abuse than are slower infusions. However, some studies of cocaine self-administration in rats have failed to support this finding, possibly because the effect was masked by other factors. One such factor may be the pairing of a stimulus with the infusion, a procedure that is known to facilitate acquisition of drug self-administration. We compared fast and slow infusions by allowing groups of rats to acquire cocaine self-administration at a dose of 1 mg/kg/infusion, delivered over different durations (1.8 or 100 sec). Two groups were trained with either short or long infusions paired with a visual stimulus change (lights off), and two other groups were trained with short or long durations but with no stimulus change. Both groups trained with a paired stimulus acquired cocaine self-administration. With no stimulus change, the rats trained with the 1.8-sec infusion acquired cocaine self-administration at a rate comparable to the two groups that were trained with a paired stimulus. However, most rats in the group trained with the 100-sec infusion that was not accompanied by a stimulus change failed to acquire cocaine self-administration. The stimulus itself did not support responding. These results indicate that infusing a given dose of cocaine over a longer duration reduces its ability to support self-administration, but drug-paired stimuli can partially mask this effect by enhancing the effectiveness of slow infusions. PMID:21600912

Rapid delivery of cocaine facilitates acquisition of self-administration in rats: an effect masked by paired stimuli.

PubMed

Schindler, Charles W; Cogan, Elizabeth S; Thorndike, Eric B; Panlilio, Leigh V

2011-09-01

In general, faster infusions of cocaine are more likely to support behavior related to abuse than are slower infusions. However, some studies of cocaine self-administration in rats have failed to support this finding, possibly because the effect was masked by other factors. One such factor may be the pairing of a stimulus with the infusion, a procedure that is known to facilitate acquisition of drug self-administration. We compared fast and slow infusions by allowing groups of rats to acquire cocaine self-administration at a dose of 1mg/kg/infusion, delivered over different durations (1.8 or 100 s). Two groups were trained with either short or long infusions paired with a visual stimulus change (lights off), and two other groups were trained with short or long durations but with no stimulus change. Both groups trained with a paired stimulus acquired cocaine self-administration. With no stimulus change, the rats trained with the 1.8-s infusion acquired cocaine self-administration at a rate comparable to the two groups that were trained with a paired stimulus. However, most rats in the group trained with the 100-s infusion that was not accompanied by a stimulus change failed to acquire cocaine self-administration. The stimulus itself did not support responding. These results indicate that infusing a given dose of cocaine over a longer duration reduces its ability to support self-administration, but drug-paired stimuli can partially mask this effect by enhancing the effectiveness of slow infusions. Published by Elsevier Inc.

Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells.

PubMed

Kuuluvainen, Emilia; Domènech-Moreno, Eva; Niemelä, Elina H; Mäkelä, Tomi P

2018-06-01

In cancer, oncogene activation is partly mediated by acquired superenhancers, which therefore represent potential targets for inhibition. Superenhancers are enriched for BRD4 and Mediator, and both BRD4 and the Mediator MED12 subunit are disproportionally required for expression of superenhancer-associated genes in stem cells. Here we show that depletion of Mediator kinase module subunit MED12 or MED13 together with MED13L can be used to reduce expression of cancer-acquired superenhancer genes, such as the MYC gene, in colon cancer cells, with a concomitant decrease in proliferation. Whereas depletion of MED12 or MED13/MED13L caused a disproportional decrease of superenhancer gene expression, this was not seen with depletion of the kinases cyclin-dependent kinase 9 (CDK8) and CDK19. MED12-MED13/MED13L-dependent superenhancer genes were coregulated by β-catenin, which has previously been shown to associate with MED12. Importantly, β-catenin depletion caused reduced binding of MED12 at the MYC superenhancer. The effect of MED12 or MED13/MED13L depletion on cancer-acquired superenhancer gene expression was more specific than and partially distinct from that of BRD4 depletion, with the most efficient inhibition seen with combined targeting. These results identify a requirement of MED12 and MED13/MED13L for expression of acquired superenhancer genes in colon cancer, implicating these Mediator subunits as potential therapeutic targets for colon cancer, alone or together with BRD4. Copyright © 2018 American Society for Microbiology.

Experimental Measurement of Frozen and Partially Melted Water Droplet Impact Dynamics

NASA Technical Reports Server (NTRS)

Palacios, Jose; Yan, Sihong; Tan, Jason; Kreeger, Richard E.

2014-01-01

High-speed video of single frozen water droplets impacting a surface was acquired. The droplets diameter ranged from 0.4 mm to 0.9 mm and impacted at velocities ranging from 140 m/sec to 309 m/sec. The techniques used to freeze the droplets and launch the particles against the surfaces is described in this paper. High-speed video was used to quantify the ice accretion area to the surface for varying impact angles (30 deg, 45 deg, 60 deg), impacting velocities, and break-up angles. An oxygen /acetylene cross-flow flame used to ensure partial melting of the traveling frozen droplets is also discussed. A linear relationship between impact angle and ice accretion is identified for fully frozen particles. The slope of the relationship is affected by impact speed. Perpendicular impacts, i.e. 30 deg, exhibited small differences in ice accretion for varying velocities, while an increase of 60% in velocity from 161 m/sec to 259 m/sec, provided an increase on ice accretion area of 96% at an impact angle of 60 deg. The increase accretion area highlights the importance of impact angle and velocity on the ice accretion process of ice crystals. It was experimentally observed that partial melting was not required for ice accretion at the tested velocities when high impact angles were used (45 and 60 deg). Partially melted droplets doubled the ice accretion areas on the impacting surface when 0.0023 Joules were applied to the particle. The partially melted state of the droplets and a method to quantify the percentage increase in ice accretion area is also described in the paper.

PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.

PubMed

Yahiaoui, Anella; Meadows, Sarah A; Sorensen, Rick A; Cui, Zhi-Hua; Keegan, Kathleen S; Brockett, Robert; Chen, Guang; Quéva, Christophe; Li, Li; Tannheimer, Stacey L

2017-01-01

Activated B-cell-like diffuse large B-cell lymphoma relies on B-cell receptor signaling to drive proliferation and survival. Downstream of the B-cell receptor, the key signaling kinases Bruton's tyrosine kinase and phosphoinositide 3-kinase δ offer opportunities for therapeutic intervention by agents such as ibrutinib, ONO/GS-4059, and idelalisib. Combination therapy with such targeted agents could provide enhanced efficacy due to complimentary mechanisms of action. In this study, we describe both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma. Significant tumor regression was observed with a combination of PI3Kδ and Bruton's tyrosine kinase inhibitors in the mouse TMD8 xenograft. Acquired resistance to idelalisib in the TMD8 cell line occurred by loss of phosphatase and tensin homolog and phosphoinositide 3-kinase pathway upregulation, but not by mutation of PIK3CD. Sensitivity to idelalisib could be restored by combining idelalisib and ONO/GS-4059. Further evaluation of targeted inhibitors revealed that the combination of idelalisib and the phosphoinositide-dependent kinase-1 inhibitor GSK2334470 or the AKT inhibitor MK-2206 could partially overcome resistance. Characterization of acquired Bruton's tyrosine kinase inhibitor resistance revealed a novel tumor necrosis factor alpha induced protein 3 mutation (TNFAIP3 Q143*), which led to a loss of A20 protein, and increased p-IκBα. The combination of idelalisib and ONO/GS-4059 partially restored sensitivity in this resistant line. Additionally, a mutation in Bruton's tyrosine kinase at C481F was identified as a mechanism of resistance. The combination activity observed with idelalisib and ONO/GS-4059, taken together with the ability to overcome resistance, could lead to a new therapeutic option in activated B-cell-like diffuse large B-cell lymphoma. A clinical trial is currently underway to evaluate the combination of idelalisib and ONO/GS-4059 (NCT02457598).

Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer.

PubMed

Dominguez-Bello, Maria G; De Jesus-Laboy, Kassandra M; Shen, Nan; Cox, Laura M; Amir, Amnon; Gonzalez, Antonio; Bokulich, Nicholas A; Song, Se Jin; Hoashi, Marina; Rivera-Vinas, Juana I; Mendez, Keimari; Knight, Rob; Clemente, Jose C

2016-03-01

Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section-delivered babies.

Does individualism help explain differences in employers' stigmatizing attitudes toward disability across Chinese and American cities?

PubMed

Rao, Deepa; Horton, Randall A; Tsang, Hector W H; Shi, Kan; Corrigan, Patrick W

2010-11-01

Stigmatizing attitudes toward people with disabilities can jeopardize such individuals' well-being and recovery through denial of employment and community isolation. By shaping social norms that define group membership, the construct of individualism may partially explain differences in stigmatizing attitudes across cultures. Further, widespread globalization has brought intensely individualistic social practices to certain segments of non-Western cultures. This paper examines whether the construct of individualism can help to explain cross-cultural differences in stigmatizing attitudes observed between American and Chinese employers. Employers (N = 879) from Beijing, Hong Kong, and Chicago provided information on their attitudes toward hiring people with disabilities, and path analyses were conducted to examine potential mediating relationships. Path analyses indicated that vertical individualism, along with perceived responsibility for acquiring a condition, partially mediated the relationship between culture and employers' negative attitudes about job candidates with disabilities. These results suggested that greater espousal of competitive and individualist values may drive stigmatizing attitudes across cultures. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Does Individualism Help Explain Differences in Employers' Stigmatizing Attitudes Toward Disability Across Chinese and American Cities?

PubMed Central

Rao, Deepa; Horton, Randall A.; Tsang, Hector W.H.; Shi, Kan; Corrigan, Patrick W.

2011-01-01

Purpose Stigmatizing attitudes toward people with disabilities can jeopardize such individuals' well-being and recovery through denial of employment and community isolation. By shaping social norms that define group membership, the construct of individualism may partially explain differences in stigmatizing attitudes across cultures. Further, widespread globalization has brought intensely individualistic social practices to certain segments of non-Western cultures. This paper examines whether the construct of individualism can help to explain cross-cultural differences in stigmatizing attitudes observed between American and Chinese employers. Design Employers (N = 879) from Beijing, Hong Kong, and Chicago provided information on their attitudes toward hiring people with disabilities, and Path Analyses were conducted to examine potential mediating relationships. Results Path analyses indicated that vertical individualism, along with perceived responsibility for acquiring a condition, partially mediated the relationship between culture and employers' negative attitudes about job candidates with disabilities. Conclusion These results suggested that greater espousal of competitive and individualist values may drive stigmatizing attitudes across cultures. PMID:21171794

Comparative Analysis of Mass Spectral Similarity Measures on Peak Alignment for Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry

PubMed Central

2013-01-01

Peak alignment is a critical procedure in mass spectrometry-based biomarker discovery in metabolomics. One of peak alignment approaches to comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) data is peak matching-based alignment. A key to the peak matching-based alignment is the calculation of mass spectral similarity scores. Various mass spectral similarity measures have been developed mainly for compound identification, but the effect of these spectral similarity measures on the performance of peak matching-based alignment still remains unknown. Therefore, we selected five mass spectral similarity measures, cosine correlation, Pearson's correlation, Spearman's correlation, partial correlation, and part correlation, and examined their effects on peak alignment using two sets of experimental GC×GC-MS data. The results show that the spectral similarity measure does not affect the alignment accuracy significantly in analysis of data from less complex samples, while the partial correlation performs much better than other spectral similarity measures when analyzing experimental data acquired from complex biological samples. PMID:24151524

Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

PubMed

Ma, W; Zhang, T-F; Lu, P; Lu, S H

2014-01-01

Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

Direct determination of danofloxacin and flumequine in milk by use of fluorescence spectrometry in combination with partial least-squares calibration.

PubMed

Murillo Pulgarín, J A; Alañón Molina, A; Boras, N

2013-03-20

A new method for the simultaneous determination of danofloxacin and flumequine in milk samples was developed by using the nonlinear variable-angle synchronous fluorescence technique to acquire data and a partial least-squares chemometric algorithm to process them. A calibration set of standard samples was designed by combination of a factorial design with two levels per factor and a central star design. Whey was used as the third component of the calibration matrix. In order to assess the goodness of the proposed method, a prediction set of 11 synthetic samples was analyzed, obtaining recovery percentages between 96.1% and 104.0%. Limits of detection, calculated by means of a new criterion, were 0.90 and 12.4 ng mL(-1) for danofloxacin and flumequine, respectively. Finally, the simultaneous determination of both fluoroquinoles in milk samples containing the analytes was successfully carried out, obtaining an average recovery percentage of 99.3 ± 4.4 for danofloxacin and 100.7 ± 4.4.

Low-Tidal-Volume Ventilation in the Acute Respiratory Distress Syndrome

PubMed Central

Malhotra, Atul

2008-01-01

A 55-year-old man who is 178 cm tall and weighs 95 kg is hospitalized with community-acquired pneumonia and progressively severe dyspnea. His arterial oxygen saturation while breathing 100% oxygen through a face mask is 76%; a chest radiograph shows diffuse alveolar infiltrates with air bronchograms. He is intubated and receives mechanical ventilation; ventilator settings include a tidal volume of 1000 ml, a positive end-expiratory pressure (PEEP) of 5 cm of water, and a fraction of inspired oxygen (FiO2) of 0.8. With these settings, peak airway pressure is 50 to 60 cm of water, plateau airway pressure is 38 cm of water, partial pressure of arterial oxygen is 120 mm Hg, partial pressure of carbon dioxide is 37 mm Hg, and arterial blood pH is 7.47. The diagnosis of the acute respiratory distress syndrome (ARDS) is made. An intensive care specialist evaluates the patient and recommends changing the current ventilator settings and implementing a low-tidal-volume ventilation strategy. PMID:17855672

Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

PubMed

Ahlgren, André; Wirestam, Ronnie; Petersen, Esben Thade; Ståhlberg, Freddy; Knutsson, Linda

2014-09-01

Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low-resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1 -based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high-resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra-subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low-resolution partial volume estimation in connection with ASL perfusion estimation is feasible, and provides a promising tool for decoupling perfusion and tissue volume. Copyright © 2014 John Wiley & Sons, Ltd.

Magnetic Evidence for a Partially Differentiated Carbonaceous Chondrite Parent Body and Possible Implications for Asteroid 21 Lutetia

NASA Astrophysics Data System (ADS)

Weiss, Benjamin; Carporzen, L.; Elkins-Tanton, L.; Shuster, D. L.; Ebel, D. S.; Gattacceca, J.; Binzel, R. P.

2010-10-01

The origin of remanent magnetization in the CV carbonaceous chondrite Allende has been a longstanding mystery. The possibility of a core dynamo like that known for achondrite parent bodies has been discounted because chondrite parent bodies are assumed to be undifferentiated. Here we report that Allende's magnetization was acquired over several million years (Ma) during metasomatism on the parent planetesimal in a > 20 microtesla field 8-9 Ma after solar system formation. This field was present too recently and directionally stable for too long to have been the generated by the protoplanetary disk or young Sun. The field intensity is in the range expected for planetesimal core dynamos (Weiss et al. 2010), suggesting that CV chondrites are derived from the outer, unmelted layer of a partially differentiated body with a convecting metallic core (Elkins-Tanton et al. 2010). This suggests that asteroids with differentiated interiors could be present today but masked under chondritic surfaces. In fact, CV chondrites are spectrally similar to many members of the Eos asteroid family whose spectral diversity has been interpreted as evidence for a partially differentiated parent asteroid (Mothe-Diniz et al. 2008). CV chondrite spectral and polarimetric data also resemble those of asteroid 21 Lutetia (e.g., Belskaya et al. 2010), recently encountered by the Rosetta spacecraft. Ground-based measurements of Lutetia indicate a high density of 2.4-5.1 g cm-3 (Drummond et al. 2010), while radar data seem to rule out a metallic surface composition (Shepard et al. 2008). If Rosetta spacecraft measurements confirm a high density and a CV-like surface composition for Lutetia, then we propose Lutetia may be an example of a partially differentiated carbonaceous chondrite parent body. Regardless, the very existence of primitive achondrites, which contain evidence of both relict chondrules and partial melting, are prima facie evidence for the formation of partially differentiated bodies.

HPV in men.

PubMed

D'Hauwers, K W M; Tjalma, W A A

2008-01-01

To collect information about HPV in men and the (possible) correlation with HVP infection in women. Review of the literature. An overview of HPV-related penile and anal malignancies in men and the risk factors of acquiring HPV. In men HPV is also partially responsible for anogenital malignancies. Although the prevalence of HPV-related malignancies in men is much lower than in women, it is useful to gain more knowlege. Especially knowing if men are really the HPV reservoir and transmitters for women can make a difference in deciding whether men should also be screened for HPV and if they are good candidates for vaccination.

Fuzzy integral-based gaze control architecture incorporated with modified-univector field-based navigation for humanoid robots.

PubMed

Yoo, Jeong-Ki; Kim, Jong-Hwan

2012-02-01

When a humanoid robot moves in a dynamic environment, a simple process of planning and following a path may not guarantee competent performance for dynamic obstacle avoidance because the robot acquires limited information from the environment using a local vision sensor. Thus, it is essential to update its local map as frequently as possible to obtain more information through gaze control while walking. This paper proposes a fuzzy integral-based gaze control architecture incorporated with the modified-univector field-based navigation for humanoid robots. To determine the gaze direction, four criteria based on local map confidence, waypoint, self-localization, and obstacles, are defined along with their corresponding partial evaluation functions. Using the partial evaluation values and the degree of consideration for criteria, fuzzy integral is applied to each candidate gaze direction for global evaluation. For the effective dynamic obstacle avoidance, partial evaluation functions about self-localization error and surrounding obstacles are also used for generating virtual dynamic obstacle for the modified-univector field method which generates the path and velocity of robot toward the next waypoint. The proposed architecture is verified through the comparison with the conventional weighted sum-based approach with the simulations using a developed simulator for HanSaRam-IX (HSR-IX).

SU-F-303-05: DCE-MRI Before and During Treatment for Prediction of Concurrent Chemotherapy and Radiation Therapy Response in Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Y; Diwanji, T; Zhang, B

2015-06-15

Purpose: To determine the ability of pharmacokinetic parameters derived from dynamic contrast-enhanced MRI (DCE- MRI) acquired before and during concurrent chemotherapy and radiation therapy to predict clinical response in patients with head and neck cancer. Methods: Eleven patients underwent a DCE-MRI scan at three time points: 1–2 weeks before treatment, 4–5 weeks after treatment initiation, and 3–4 months after treatment completion. Post-processing of MRI data included correction to reduce motion artifacts. The arterial input function was obtained by measuring the dynamic tracer concentration in the jugular veins. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), rate constant (Kep;more » Kep = Ktrans/ve), and plasma volume fraction (vp) were computed for primary tumors and cervical nodal masses. Patients were categorized into two groups based on response to therapy at 3–4 months: responders (no evidence of disease) and partial responders (regression of disease). Responses of the primary tumor and nodes were evaluated separately. A linear classifier and receiver operating characteristic curve analyses were used to determine the best model for discrimination of responders from partial responders. Results: When the above pharmacokinetic parameters of the primary tumor measured before and during treatment were incorporated into the linear classifier, a discriminative accuracy of 88.9%, with sensitivity =100% and specificity = 66.7%, was observed between responders (n=6) and partial responders (n=3) for the primary tumor with the corresponding accuracy = 44.4%, sensitivity = 66.7%, and specificity of 0% for nodal masses. When only pre-treatment parameters were used, the accuracy decreased to 66.7%, with sensitivity = 66.7% and specificity = 66.7% for the primary tumor and decreased to 33.3%, sensitivity of 50%, and specificity of 0% for nodal masses. Conclusion: Higher accuracy, sensitivity, and specificity were obtained using DCE-MRI-derived pharmacokinetic parameters acquired before and during treatment as compared with those derived from the pre-treatment time-point, exclusively.« less

SU-G-JeP1-15: Sliding Window Prior Data Assisted Compressed Sensing for MRI Lung Tumor Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yip, E; Wachowicz, K; Rathee, S

Purpose: Prior Data Assisted Compressed Sensing (PDACS) is a partial k-space acquisition and reconstruction method for mobile tumour (i.e. lung) tracking using on-line MRI in radiotherapy. PDACS partially relies on prior data acquired at the beginning of dynamic scans, and is therefore susceptible to artifacts in longer duration scan due to slow drifts in MR signal. A novel sliding window strategy is presented to mitigate this effect. Methods: MRI acceleration is simulated by retrospective removal of data from the fully sampled sets. Six lung cancer patients were scanned (clinical 3T MRI) using a balanced steady state free precession (bSSFP) sequencemore » for 3 minutes at approximately 4 frames per second, for a total of 650 dynamics. PDACS acceleration is achieved by undersampling of k-space in a single pseudo-random pattern. Reconstruction iteratively minimizes the total variations while constraining the images to satisfy both the currently acquired data and the prior data in missing k-space. Our novel sliding window technique (SW-PDACS), uses a series of distinct pseudo-random under-sampling patterns of partial k-space – with the prior data drawn from a sliding window of the most recent data available. Under-sampled data, simulating 2 – 5x acceleration are reconstructed using PDACS and SW-PDACS. Three quantitative metrics: artifact power, centroid error and Dice’s coefficient are computed for comparison. Results: Quantitively metric values from all 6 patients are averaged in 3 bins, each containing approximately one minute of dynamic data. For the first minute bin, PDACS and SW-PDACS give comparable results. Progressive decline in image quality metrics in bins 2 and 3 are observed for PDACS. No decline in image quality is observed for SW-PDACS. Conclusion: The novel approach presented (SW-PDACS) is a more robust for accelerating longer duration (>1 minute) dynamic MRI scans for tracking lung tumour motion using on-line MRI in radiotherapy. B.G. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russ, M; Shankar, A; Lau, A

Purpose: Demonstrate and quantify the augmented resolution due to focalspot size decrease in images acquired on the anode side of the field, for both small and medium (0.3 and 0.6mm) focal-spot sizes using the experimental task-based GM-ROD metric. Theoretical calculations have shown that a medium focal-spot can achieve the resolution of a small focal-spot if acquired with a tilted anode, effectively providing a higher-output small focal-spot. Methods: The MAF-CMOS (micro-angiographic fluoroscopic complementary-metal-oxide semiconductor) detector (75µm pixel pitch) imaged two copper wire segments of different diameter and a pipeline stent at the central axis and on the anode side of themore » beam, achieved by tilting the x-ray C-arm (Toshiba Infinix) to 6° and realigning the detector with the perpendicular ray to correct for x-ray obliquity. The relative gain in resolution was determined using the GM-ROD metric, which compares images on the basis of the Fourier transform of the image and the measured NNPS. To emphasize the geometric unsharpness, images were acquired at a magnification of two. Results: Images acquired on the anode side were compared to those acquired on the central axis with the same target-area focal-spot to consider the effect of an angled tube, and for all three objects the advantage of the smaller effective focal-spot was clear, showing a maximum improvement of 36% in GM-ROD. The images obtained with the small focal-spot at the central axis were compared to those of the medium focal-spot at the anode side and, for all objects, the relative performance was comparable. Conclusion: For three objects, the GM-ROD demonstrated the advantage of the anode side focal-spot. The comparable performance of the medium focal-spot on the anode side will allow for a high-output small focal-spot; a necessity in endovascular image-guided interventions. Partial support from an NIH grant R01EB002873 and an equipment grant from Toshiba Medical Systems Corp.« less

An acquired HER2 T798I gatekeeper mutation induces resistance to neratinib in a patient with HER2 mutant-driven breast cancer

PubMed Central

Hanker, Ariella B.; Brewer, Monica Red; Sheehan, Jonathan H.; Koch, James P.; Sliwoski, Gregory R.; Nagy, Rebecca; Lanman, Richard; Berger, Michael F.; Hyman, David M.; Solit, David B.; He, Jie; Miller, Vincent; Cutler, Richard E.; Lalani, Alshad S.; Cross, Darren; Lovly, Christine M.; Meiler, Jens; Arteaga, Carlos L.

2017-01-01

We report a HER2T798I gatekeeper mutation in a patient with HER2L869R-mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3E928G, also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2L869R but not HER2L869R/T798I. In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2L869R/T798I-induced signaling and cell growth. Acquisition of HER2T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2L869R is a driver mutation. HER2T798I-mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib. PMID:28274957

Measurement of an Evaporating Drop on a Reflective Substrate

NASA Technical Reports Server (NTRS)

Chao, David F.; Zhang, Nengli

2004-01-01

A figure depicts an apparatus that simultaneously records magnified ordinary top-view video images and laser shadowgraph video images of a sessile drop on a flat, horizontal substrate that can be opaque or translucent and is at least partially specularly reflective. The diameter, contact angle, and rate of evaporation of the drop as functions of time can be calculated from the apparent diameters of the drop in sequences of the images acquired at known time intervals, and the shadowgrams that contain flow patterns indicative of thermocapillary convection (if any) within the drop. These time-dependent parameters and flow patterns are important for understanding the physical processes involved in the spreading and evaporation of drops. The apparatus includes a source of white light and a laser (both omitted from the figure), which are used to form the ordinary image and the shadowgram, respectively. Charge-coupled-device (CCD) camera 1 (with zoom) acquires the ordinary video images, while CCD camera 2 acquires the shadowgrams. With respect to the portion of laser light specularly reflected from the substrate, the drop acts as a plano-convex lens, focusing the laser beam to a shadowgram on the projection screen in front of CCD camera 2. The equations for calculating the diameter, contact angle, and rate of evaporation of the drop are readily derived on the basis of Snell s law of refraction and the geometry of the optics.

Implementation of cost-effective diffuse light source mechanism to reduce specular reflection and halo effects for resistor-image processing

NASA Astrophysics Data System (ADS)

Chen, Yung-Sheng; Wang, Jeng-Yau

2015-09-01

Light source plays a significant role to acquire a qualified image from objects for facilitating the image processing and pattern recognition. For objects possessing specular surface, the phenomena of reflection and halo appearing in the acquired image will increase the difficulty of information processing. Such a situation may be improved by the assistance of valuable diffuse light source. Consider reading resistor via computer vision, due to the resistor's specular reflective surface it will face with a severe non-uniform luminous intensity on image yielding a higher error rate in recognition without a well-controlled light source. A measurement system including mainly a digital microscope embedded in a replaceable diffuse cover, a ring-type LED embedded onto a small pad carrying a resistor for evaluation, and Arduino microcontrollers connected with PC, is presented in this paper. Several replaceable cost-effective diffuse covers made by paper bowl, cup and box inside pasted with white paper are presented for reducing specular reflection and halo effects and compared with a commercial diffuse some. The ring-type LED can be flexibly configured to be a full or partial lighting based on the application. For each self-made diffuse cover, a set of resistors with 4 or 5 color bands are captured via digital microscope for experiments. The signal-to-noise ratio from the segmented resistor-image is used for performance evaluation. The detected principal axis of resistor body is used for the partial LED configuration to further improve the lighting condition. Experimental results confirm that the proposed mechanism can not only evaluate the cost-effective diffuse light source but also be extended as an automatic recognition system for resistor reading.

Methods for the correction of vascular artifacts in PET O-15 water brain-mapping studies

NASA Astrophysics Data System (ADS)

Chen, Kewei; Reiman, E. M.; Lawson, M.; Yun, Lang-sheng; Bandy, D.; Palant, A.

1996-12-01

While positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) can be used to map brain regions that are involved in normal and pathological human behaviors, measurements in the anteromedial temporal lobe can be confounded by the combined effects of radiotracer activity in neighboring arteries and partial-volume averaging. The authors now describe two simple methods to address this vascular artifact. One method utilizes the early frames of a dynamic PET study, while the other method utilizes a coregistered magnetic resonance image (MRI) to characterize the vascular region of interest (VROI). Both methods subsequently assign a common value to each pixel in the VROI for the control (baseline) scan and the activation scan. To study the vascular artifact and to demonstrate the ability of the proposed methods correcting the vascular artifact, four dynamic PET scans were performed in a single subject during the same behavioral state. For each of the four scans, a vascular scan containing vascular activity was computed as the summation of the images acquired 0-60 s after radiotracer administration, and a control scan containing minimal vascular activity was computed as the summation of the images acquired 20-80 s after radiotracer administration. t-score maps calculated from the four pairs of vascular and control scans were used to characterize regional blood flow differences related to vascular activity before and after the application of each vascular artifact correction method. Both methods eliminated the observed differences in vascular activity, as well as the vascular artifact observed in the anteromedial temporal lobes. Using PET data from a study of normal human emotion, these methods permitted the authors to identify rCBF increases in the anteromedial temporal lobe free from the potentially confounding, combined effects of vascular activity and partial-volume averaging.

Plant Line Trial Evaluation of Viable Non-Chromium Passivation Systems for Electrolytin Tinplate, ETP (TRP 9911)

DOE Office of Scientific and Technical Information (OSTI.GOV)

John A. Sinsel

2003-06-30

Plant trial evaluations have been completed for two zirconium-based, non-chromium passivation systems previously identified as possible alternatives to cathodic dichromate (CDC) passivation for electrolytic tinplate (ETP). These trials were done on a commercial electrolytic tin plating line at Weirton Steel and extensive evaluations of the materials resulting from these trials have been completed. All this was accomplished as a collaborative effort under the AISI Technology Roadmap Program and was executed by seven North American Tin Mill Products producers [Bethlehem Steel (now acquired by International Steel Group (ISG)), Dofasco Inc., National Steel (now acquired by U.S. Steel), U.S. Steel, USS-Posco, Weirtonmore » Steel, and Wheeling-Pittsburgh Steel] with funding partially from the Department of Energy (DOE) and partially on an equal cost sharing basis among project participants. The initial phases of this project involved optimization of application procedures for the non-chromium systems in the laboratories at Bethlehem Steel and Betz Dearborn followed by extensive testing with various lacquer formulations and food simulants in the laboratories at Valspar and PPG. Work was also completed at Dofasco and Weirton Steel to develop methods to prevent precipitation of insoluble solids as a function of time from the zirconate system. The results of this testing indicated that sulfide staining characteristics for the non-chromium passivation systems could be minimized but not totally eliminated and neither system was found to perform quite as good, in this respect, as the standard CDC system. As for the stability of zirconate treatment, a method was developed to stabilize this system for a sufficient period of time to conduct plant trial evaluations but, working with a major supplier of zirconium orthosulfate, a method for long term stabilization is still under development.« less

Lipopolysaccharide loss produces partial colistin dependence and collateral sensitivity to azithromycin, rifampicin and vancomycin in Acinetobacter baumannii.

PubMed

García-Quintanilla, Meritxell; Carretero-Ledesma, Marta; Moreno-Martínez, Patricia; Martín-Peña, Reyes; Pachón, Jerónimo; McConnell, Michael J

2015-12-01

Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved in lipid A biosynthesis (lpxA, lpxC and lpxD). The objective of this study was to characterise the susceptibility to 15 clinically relevant antibiotics and 6 antimicrobial peptides (AMPs) of MDR A. baumannii clinical isolates that acquired colistin resistance due to mutations in lpxA, lpxC and lpxD as well as their colistin-susceptible counterparts. A dramatic increase in antibiotic susceptibility (≥16-fold increase) was observed upon LPS loss for azithromycin, rifampicin and vancomycin, whereas a moderate increase in susceptibility was seen for amikacin, ceftazidime, imipenem, cefepime and meropenem. Importantly, concentrations ranging from 8 mg/L to 32 mg/L of the six AMPs were able to reduce bacterial viability by ≥3 log10 in growth curve assays. We also demonstrate that colistin resistance results in partial colistin dependence for growth in LPS-deficient strains containing mutations in lpxA, lpxC and lpxD, but not when colistin resistance occurs via LPS modification due to mutations in the PmrA/B two-component system. The results of this study indicate that loss of LPS expression results in collateral sensitivity to azithromycin, rifampicin and vancomycin, and that the six AMPs tested retain activity against LPS-deficient strains, indicating that these antibiotics may be viable treatment options for infections caused by these strains. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

A 3-dimensional mathematic cylinder phantom for the evaluation of the fundamental performance of SPECT.

PubMed

Onishi, Hideo; Motomura, Nobutoku; Takahashi, Masaaki; Yanagisawa, Masamichi; Ogawa, Koichi

2010-03-01

Degradation of SPECT images results from various physical factors. The primary aim of this study was the development of a digital phantom for use in the characterization of factors that contribute to image degradation in clinical SPECT studies. A 3-dimensional mathematic cylinder (3D-MAC) phantom was devised and developed. The phantom (200 mm in diameter and 200 mm long) comprised 3 imbedded stacks of five 30-mm-long cylinders (diameters, 4, 10, 20, 40, and 60 mm). In simulations, the 3 stacks and the background were assigned radioisotope concentrations and attenuation coefficients. SPECT projection datasets that included Compton scattering effects, photoelectric effects, and gamma-camera models were generated using the electron gamma-shower Monte Carlo simulation program. Collimator parameters, detector resolution, total photons acquired, number of projections acquired, and radius of rotation were varied in simulations. The projection data were formatted in Digital Imaging and Communications in Medicine (DICOM) and imported to and reconstructed using commercial reconstruction software on clinical SPECT workstations. Using the 3D-MAC phantom, we validated that contrast depended on size of region of interest (ROI) and was overestimated when the ROI was small. The low-energy general-purpose collimator caused a greater partial-volume effect than did the low-energy high-resolution collimator, and contrast in the cold region was higher using the filtered backprojection algorithm than using the ordered-subset expectation maximization algorithm in the SPECT images. We used imported DICOM projection data and reconstructed these data using vendor software; in addition, we validated reconstructed images. The devised and developed 3D-MAC SPECT phantom is useful for the characterization of various physical factors, contrasts, partial-volume effects, reconstruction algorithms, and such, that contribute to image degradation in clinical SPECT studies.

Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate-Importance of proliferative activity of tubular cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Yuan; Fujigaki, Yoshihide, E-mail: yf0516@hama-med.ac.j; Sakakima, Masanori

Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PTmore » cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.« less

Interior tomography in microscopic CT with image reconstruction constrained by full field of view scan at low spatial resolution

NASA Astrophysics Data System (ADS)

Luo, Shouhua; Shen, Tao; Sun, Yi; Li, Jing; Li, Guang; Tang, Xiangyang

2018-04-01

In high resolution (microscopic) CT applications, the scan field of view should cover the entire specimen or sample to allow complete data acquisition and image reconstruction. However, truncation may occur in projection data and results in artifacts in reconstructed images. In this study, we propose a low resolution image constrained reconstruction algorithm (LRICR) for interior tomography in microscopic CT at high resolution. In general, the multi-resolution acquisition based methods can be employed to solve the data truncation problem if the project data acquired at low resolution are utilized to fill up the truncated projection data acquired at high resolution. However, most existing methods place quite strict restrictions on the data acquisition geometry, which greatly limits their utility in practice. In the proposed LRICR algorithm, full and partial data acquisition (scan) at low and high resolutions, respectively, are carried out. Using the image reconstructed from sparse projection data acquired at low resolution as the prior, a microscopic image at high resolution is reconstructed from the truncated projection data acquired at high resolution. Two synthesized digital phantoms, a raw bamboo culm and a specimen of mouse femur, were utilized to evaluate and verify performance of the proposed LRICR algorithm. Compared with the conventional TV minimization based algorithm and the multi-resolution scout-reconstruction algorithm, the proposed LRICR algorithm shows significant improvement in reduction of the artifacts caused by data truncation, providing a practical solution for high quality and reliable interior tomography in microscopic CT applications. The proposed LRICR algorithm outperforms the multi-resolution scout-reconstruction method and the TV minimization based reconstruction for interior tomography in microscopic CT.

Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway

PubMed Central

Attar, Narsis; Ng, Charles; Chu, Connie; Guo, Deliang; Nazarian, Ramin; Chmielowski, Bartosz; Glaspy, John A.; Comin-Anduix, Begonya; Mischel, Paul S.; Lo, Roger S.; Ribas, Antoni

2011-01-01

Background The sustained clinical activity of the BRAF inhibitor vemurafenib (PLX4032/RG7204) in patients with BRAFV600 mutant melanoma is limited primarily by the development of acquired resistance leading to tumor progression. Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway. Methodology/Principal Findings The sensitivity to vemurafenib or the MEK inhibitor AZD6244 was tested in sensitive and resistant human melanoma cell lines exploring differences in activation-associated phosphorylation levels of major signaling molecules, leading to the testing of co-inhibition of the AKT/mTOR pathway genetically and pharmacologically. There was a high degree of cross-resistance to vemurafenib and AZD6244, except in two vemurafenib-resistant cell lines that acquired a secondary mutation in NRAS. In other cell lines, acquired resistance to both drugs was associated with persistence or increase in activity of AKT pathway. siRNA-mediated gene silencing and combination therapy with an AKT inhibitor or rapamycin partially or completely reversed the resistance. Conclusions/Significance Primary and acquired resistance to vemurafenib in these in vitro models results in frequent cross resistance to MEK inhibitors, except when the resistance is the result of a secondary NRAS mutation. Resistance to BRAF or MEK inhibitors is associated with the induction or persistence of activity within the AKT pathway in the presence of these drugs. This resistance can be potentially reversed by the combination of a RAF or MEK inhibitor with an AKT or mTOR inhibitor. These combinations should be available for clinical testing in patients progressing on BRAF inhibitors. PMID:22194965

Changes in articular cartilage following arthroscopic partial medial meniscectomy.

PubMed

Eichinger, Martin; Schocke, Michael; Hoser, Christian; Fink, Christian; Mayr, Raul; Rosenberger, Ralf E

2016-05-01

To examine degenerative changes in all cartilage surfaces of the knee following arthroscopic partial medial meniscectomy. For this prospective cohort study, 14 patients (five female) with a mean age of 47.9 ± 12.9 years who had undergone isolated arthroscopic partial medial meniscectomy were evaluated. Cartilage-sensitive magnetic resonance imaging (MRI) scans were acquired from the operated knees before the index operations, as well as at 6, 12, and 24 months after surgery. The MRI scans were assessed for the prevalence, severity, and size of cartilage degenerations. The clinical outcome was assessed using the SF-36 physical and mental component score and the International Knee Documentation Committee Knee Evaluation Form and was correlated with radiological findings. There was a significant increase in the severity of cartilage lesions in the medial tibial plateau (P = 0.019), as well as a trend towards an increase in the lateral tibial plateau. The size of the cartilage lesions increased significantly in the medial femoral condyle (P = 0.005) and lateral femoral condyle (P = 0.029), as well as in the patella (P = 0.019). Functional outcome scores improved significantly throughout the follow-up period. There was no correlation between cartilage wear and functional outcome. Arthroscopic partial medial meniscectomy is associated with adverse effects on articular cartilage and may lead to an increase in the severity and size of cartilage lesions. Post-operative cartilage wear predominantly affected the medial compartment and also affected the other compartments of the knee. Strategies to reduce subsequent osteoarthritic changes need to involve all compartments of the knee. IV.

Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy.

PubMed

Takahashi, Kazuhiro; Kurokawa, Tomohiro; Oshiro, Yukio; Fukunaga, Kiyoshi; Sakashita, Shingo; Ohkohchi, Nobuhiro

2016-05-01

Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade ≤ II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage ≤ 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P < 0.01) and morbidity (OR, 4.90; P < 0.01). Furthermore, patients with the lowest platelet percentage ≤ 60% had decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage ≥ 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy.

Cold rescue of the thermolabile tailspike intermediate at the junction between productive folding and off-pathway aggregation.

PubMed Central

Betts, S. D.; King, J.

1998-01-01

Off-pathway intermolecular interactions between partially folded polypeptide chains often compete with correct intramolecular interactions, resulting in self-association of folding intermediates into the inclusion body state. Intermediates for both productive folding and off-pathway aggregation of the parallel beta-coil tailspike trimer of phage P22 have been identified in vivo and in vitro using native gel electrophoresis in the cold. Aggregation of folding intermediates was suppressed when refolding was initiated and allowed to proceed for a short period at 0 degrees C prior to warming to 20 degrees C. Yields of refolded tailspike trimers exceeding 80% were obtained using this temperature-shift procedure, first described by Xie and Wetlaufer (1996, Protein Sci 5:517-523). We interpret this as due to stabilization of the thermolabile monomeric intermediate at the junction between productive folding and off-pathway aggregation. Partially folded monomers, a newly identified dimer, and the protrimer folding intermediates were populated in the cold. These species were electrophoretically distinguished from the multimeric intermediates populated on the aggregation pathway. The productive protrimer intermediate is disulfide bonded (Robinson AS, King J, 1997, Nat Struct Biol 4:450-455), while the multimeric aggregation intermediates are not disulfide bonded. The partially folded dimer appears to be a precursor to the disulfide-bonded protrimer. The results support a model in which the junctional partially folded monomeric intermediate acquires resistance to aggregation in the cold by folding further to a conformation that is activated for correct recognition and subunit assembly. PMID:9684883

Sexual difficulties in people living with HIV in France--results from a large representative sample of outpatients attending French hospitals (ANRS-EN12-VESPA).

PubMed

Bouhnik, Anne-Déborah; Préau, Marie; Schiltz, Marie-Ange; Obadia, Yolande; Spire, Bruno

2008-07-01

We analysed sexual difficulties in a nationally representative sample of HIV-infected outpatients in France. Analyses were restricted to the 1,812 HIV-treated participants who reported at least one sexual partner during the 12 months prior to the study. The sample included 40.6% homosexual men and 24.4% women; 68.1% had a steady partner and 48.2% reported casual partners. Sexual difficulties were reported by 33.3% of the selected individuals and were more frequent in those with low sexual activity. Immuno-virological outcomes were not associated with sexual difficulties. After multiple adjustment for sexual frequency and antidepressant consumption, it was found that a larger HIV-network, reporting HIV-discrimination from friends and/or sexual partners, suffering from lipodystrophy and reporting very disturbing HIV-related symptoms were all significantly associated with sexual difficulties. HIV and HIV-treatment experience are associated with sexual difficulties. Psychological support focused on HIV-experience should be tested as a possible tool for improving sexual quality of life.

[Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

PubMed

Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

2015-01-01

Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

The Effects of Leptin Replacement on Neural Plasticity

PubMed Central

Paz-Filho, Gilberto J.

2016-01-01

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function. PMID:26881138

The Effects of Leptin Replacement on Neural Plasticity.

PubMed

Paz-Filho, Gilberto J

2016-01-01

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.

Leptin, An Adipokine With Central Importance in the Global Obesity Problem.

PubMed

Mechanick, Jeffrey I; Zhao, Shan; Garvey, W Timothy

2017-12-13

Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

PubMed Central

Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed

2012-01-01

The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493

Lamina-independent lamins in the nuclear interior serve important functions.

PubMed

Dechat, T; Gesson, K; Foisner, R

2010-01-01

Nuclear lamins were originally described as the main constituents of the nuclear lamina, a filamentous meshwork closely associated with the inner nuclear membrane. However, within recent years, it has become increasingly evident that a fraction of lamins also resides throughout the nuclear interior. As intermediate-filament-type proteins, lamins have been suggested to fulfill mainly structural functions such as providing shape and mechanical stability to the nucleus. But recent findings show that both peripheral and nucleoplasmic lamins also have important roles in essential cellular processes such as transcription, DNA replication, cell cycle progression, and chromatin organization. Furthermore, more than 300 mutations in the gene encoding A-type lamins have been associated with several human diseases now generally termed laminopathies and comprising muscular dystrophies, lipodystrophies, cardiomyopathies, and premature aging diseases. This review focuses on the lamina-independent pool of lamins in the nuclear interior, which surprisingly has not been studied in much detail so far. We discuss the properties and regulation of nucleoplasmic lamins during the cell cycle, their interaction partners, and their potential involvement in cellular processes and the development of laminopathies.

Construction and validation of the chronic acquired polyneuropathy patient-reported index, “CAP-PRI:” a disease-specific, health-related quality of life instrument

PubMed Central

Gwathmey, Kelly G.; Conaway, Mark R.; Seyedsadjadi, Reza; Joshi, Amruta; Barnett, Carolina; Bril, Vera; Ng, Eduardo; David, William; Gable, Karissa; Guptill, Jeffrey T.; Hobson-Webb, Lisa D.; Dineen, Jennifer; Hehir, Michael; Brannagan, Thomas H.; Byun, Esther; Adler, Margaret; Burns, Ted M.

2016-01-01

Introduction Generic health-related quality of life (HRQOL) patient-reported outcome measures have been used in patients with chronic immune-mediated polyneuropathies. We have created a disease-specific HRQOL instrument. Methods and Results The 15-item chronic acquired polyneuropathy patient-reported index (CAP-PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed from a prospective, 5-center study involving chronic immune-mediated polyneuropathy patients. Data analysis suggested modification to a 15-item scale with 3 response categories, rather than 5. The final CAP-PRI was then validated in another prospective, 5-center study. The CAP-PRI appeared to be a unidimensional outcome measure that fits the Rasch Partial Credit Model in our multicenter cohort. It correlated appropriately with the outcome measures commonly used in this patient population. Discussion The CAP-PRI is a simple, easy, disease-specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. PMID:26600438

Acquired amnesia in childhood: a single case study.

PubMed

Vicari, Stefano; Menghini, Deny; Di Paola, Margherita; Serra, Laura; Donfrancesco, Alberto; Fidani, Paola; Milano, Giuseppe Maria; Carlesimo, Giovanni Augusto

2007-03-02

We report the case of C.L., an 8-year-old child who, following the surgical removal of an ependymoma from the left cerebral ventricle at the age of 4 years, developed significant difficulties in retaining day-to-day events and information. A thorough neuropsychological analysis documented in C.L. a severe anterograde amnesic syndrome, characterised by normal short-term memory, but poor performance on episodic long-term memory tests. In particular, C.L. demonstrated virtually no ability to recollect new verbal information several minutes after the presentation. As for semantic memory, C.L. demonstrated general semantic competencies, which, depending on the test, ranged from the level of a 6-year-old girl to a level corresponding to her actual chronological age. Finding a patient who, despite being severely impaired in the ability to recollect new episodic memories, still demonstrates at least partially preserved abilities to acquire new semantic knowledge suggests that neural circuits implicated in the memorisation of autobiographical events and factual information do not overlap completely. This case is examined in the light of growing literature concerned with the dissociation between episodic and semantic memory in childhood amnesia.

Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation

PubMed Central

Li, Ming; Wang, Rui; Xiang, Hua

2014-01-01

The prokaryotic immune system CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) adapts to foreign invaders by acquiring their short deoxyribonucleic acid (DNA) fragments as spacers, which guide subsequent interference to foreign nucleic acids based on sequence matching. The adaptation mechanism avoiding acquiring ‘self’ DNA fragments is poorly understood. In Haloarcula hispanica, we previously showed that CRISPR adaptation requires being primed by a pre-existing spacer partially matching the invader DNA. Here, we further demonstrate that flanking a fully-matched target sequence, a functional PAM (protospacer adjacent motif) is still required to prime adaptation. Interestingly, interference utilizes only four PAM sequences, whereas adaptation-priming tolerates as many as 23 PAM sequences. This relaxed PAM selectivity explains how adaptation-priming maximizes its tolerance of PAM mutations (that escape interference) while avoiding mis-targeting the spacer DNA within CRISPR locus. We propose that the primed adaptation, which hitches and cooperates with the interference pathway, distinguishes target from non-target by CRISPR ribonucleic acid guidance and PAM recognition. PMID:24803673

Karst landforms revealed at various scales using LiDAR and UAV in semi-arid Brazil: Consideration on karstification processes and methodological constraints

NASA Astrophysics Data System (ADS)

Silva, Orildo L.; Bezerra, Francisco H. R.; Maia, Rubson P.; Cazarin, Caroline L.

2017-10-01

This paper analyzes different types of karst landforms and their relationships with fracture systems, sedimentary bedding, and fluvial processes. We mapped karst features in the Cretaceous carbonates of the Jandaíra Formation in the Potiguar Basin, Brazil. We used high-resolution digital elevation models acquired using LiDAR and aerial orthophotographs acquired using an unmanned aerial vehicle (UAV). We grouped and described karst evolution according to scale and degree of karstification. These degrees of karst evolution are coeval. Fractures are opened by dissolution, forming vertical fluid conduits, whereas coeval dissolution occurs along horizontal layers. This conduit system acts as pathways for water flow. The enlargement of conduits contributes to the collapse of blocks in sinkholes and expansion of caves during an intermediate degree of karstification. Propagation of dissolution can cause the coalescence of sinkholes and the capture of small streams. Fluvial processes dominate karst dissolution at an advanced degree of karstification. Comparisons with previously published ground-penetrating radar (GPR), borehole and seismic surveys in sedimentary basins indicate that these structures can be partially preserved during burial.

Topological Nodal Cooper Pairing in Doped Weyl Metals

NASA Astrophysics Data System (ADS)

Li, Yi; Haldane, F. D. M.

2018-02-01

We generalize the concept of Berry connection of the single-electron band structure to that of a two-particle Cooper pairing state between two Fermi surfaces with opposite Chern numbers. Because of underlying Fermi surface topology, the pairing Berry phase acquires nontrivial monopole structure. Consequently, pairing gap functions have topologically protected nodal structure as vortices in the momentum space with the total vorticity solely determined by the pair monopole charge qp. The nodes of gap function behave as the Weyl-Majorana points of the Bogoliubov-de Gennes pairing Hamiltonian. Their relation with the connection patterns of the surface modes from the Weyl band structure and the Majorana surface modes inside the pairing gap is also discussed. Under the approximation of spherical Fermi surfaces, the pairing symmetry are represented by monopole harmonic functions. The lowest possible pairing channel carries angular momentum number j =|qp|, and the corresponding gap functions are holomorphic or antiholomorphic functions on Fermi surfaces. After projected on the Fermi surfaces with nontrivial topology, all the partial-wave channels of pairing interactions acquire the monopole charge qp independent of concrete pairing mechanism.

Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro.

PubMed Central

Tsang, K Y; Fudenberg, H H; Galbraith, G M; Donnelly, R P; Bishop, L R; Koopmann, W R

1985-01-01

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration. PMID:2581997

Performance Test Data Analysis of Scintillation Cameras

NASA Astrophysics Data System (ADS)

Demirkaya, Omer; Mazrou, Refaat Al

2007-10-01

In this paper, we present a set of image analysis tools to calculate the performance parameters of gamma camera systems from test data acquired according to the National Electrical Manufacturers Association NU 1-2001 guidelines. The calculation methods are either completely automated or require minimal user interaction; minimizing potential human errors. The developed methods are robust with respect to varying conditions under which these tests may be performed. The core algorithms have been validated for accuracy. They have been extensively tested on images acquired by the gamma cameras from different vendors. All the algorithms are incorporated into a graphical user interface that provides a convenient way to process the data and report the results. The entire application has been developed in MATLAB programming environment and is compiled to run as a stand-alone program. The developed image analysis tools provide an automated, convenient and accurate means to calculate the performance parameters of gamma cameras and SPECT systems. The developed application is available upon request for personal or non-commercial uses. The results of this study have been partially presented in Society of Nuclear Medicine Annual meeting as an InfoSNM presentation.

NASA Spacecraft Views Aftermath of Texas Floods

NASA Image and Video Library

2015-06-02

The torrential rains that lashed Texas in late May 2015 caused widespread flooding and devastation. Now that skies have partially cleared, evidence of the excessive water can still be seen in this image, acquired June 1, 2015 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument on NASA's Terra spacecraft. Located south of San Antonio, the Nueces River was one of many that overflowed its banks, sending water into adjacent fields and towns. The image covers an area of 23 by 13 miles (37 by 21 kilometers), and is located at 28.2 degrees north, 99 degrees west. http://photojournal.jpl.nasa.gov/catalog/PIA19681

A new generalized exponential rational function method to find exact special solutions for the resonance nonlinear Schrödinger equation

NASA Astrophysics Data System (ADS)

Ghanbari, Behzad; Inc, Mustafa

2018-04-01

The present paper suggests a novel technique to acquire exact solutions of nonlinear partial differential equations. The main idea of the method is to generalize the exponential rational function method. In order to examine the ability of the method, we consider the resonant nonlinear Schrödinger equation (R-NLSE). Many variants of exact soliton solutions for the equation are derived by the proposed method. Physical interpretations of some obtained solutions is also included. One can easily conclude that the new proposed method is very efficient and finds the exact solutions of the equation in a relatively easy way.

Determine utility of ERTS-1 to detect and monitor area strip mining and reclamation. [southeastern Ohio

NASA Technical Reports Server (NTRS)

Rogers, R. H. (Principal Investigator); Pettyjohn, W. A.

1975-01-01

The author has identified the following significant results. Computer techniques were applied to process ERTS tapes acquired over coal mining operations in southeastern Ohio on 21 August 1972 and 3 September 1973. ERTS products obtained included geometrically correct map overlays showing stripped earth, partially reclaimed earth, water, and natural vegetation. Computer-generated tables listing the area covered by each land-water category in square kilometers and acres were produced. By comparing these mapping products, the study demonstrates the capability of ERTS to monitor changes in the extent of stripping, success of reclamation, and the secondary effects of mining on the environment.

Image scanning microscopy using a SPAD detector array (Conference Presentation)

NASA Astrophysics Data System (ADS)

Castello, Marco; Tortarolo, Giorgio; Buttafava, Mauro; Tosi, Alberto; Sheppard, Colin J. R.; Diaspro, Alberto; Vicidomini, Giuseppe

2017-02-01

The use of an array of detectors can help overcoming the traditional limitation of confocal microscopy: the compromise between signal and theoretical resolution. Each element independently records a view of the sample and the final image can be reconstructed by pixel reassignment or by inverse filtering (e.g. deconvolution). In this work, we used a SPAD array of 25 detectors specifically designed for this goal and our scanning microscopy control system (Carma) to acquire the partial images and to perform online image processing. Further work will be devoted to optimize the image reconstruction step and to improve the fill-factor of the detector.

Autoshaping a leverpress in rats with lateral, medial, or complete septal lesions.

PubMed

Poplawsky, A; Phillips, C L

1986-05-01

Rats with either control operations or lateral, medial, or complete septal lesions received 600 trials of leverpress training using an autoshaping procedure, i.e., food delivery followed a 10 s illuminated lever presentation, or occurred immediately after a leverpress. Rats with complete septal lesions acquired the leverpress faster than controls and had more food-tray entries per minute during the first 100 trials than the other groups. Rats with lateral or medial septal lesions had leverpress and food-tray entries equivalent to controls. The facilitation of autoshaping a leverpress may partially be explained by the general increase in motor reactivity to stimuli found following septal lesions.

Identification of vapor-phase chemical warfare agent simulants and rocket fuels using laser-induced breakdown spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stearns, Jaime A.; McElman, Sarah E.; Dodd, James A.

2010-05-01

Application of laser-induced breakdown spectroscopy (LIBS) to the identification of security threats is a growing area of research. This work presents LIBS spectra of vapor-phase chemical warfare agent simulants and typical rocket fuels. A large dataset of spectra was acquired using a variety of gas mixtures and background pressures and processed using partial least squares analysis. The five compounds studied were identified with a 99% success rate by the best method. The temporal behavior of the emission lines as a function of chamber pressure and gas mixture was also investigated, revealing some interesting trends that merit further study.

Recovery of chemical Estimates by Field Inhomogeneity Neighborhood Error Detection (REFINED): Fat/Water Separation at 7T

PubMed Central

Narayan, Sreenath; Kalhan, Satish C.; Wilson, David L.

2012-01-01

I.Abstract Purpose To reduce swaps in fat-water separation methods, a particular issue on 7T small animal scanners due to field inhomogeneity, using image postprocessing innovations that detect and correct errors in the B0 field map. Materials and Methods Fat-water decompositions and B0 field maps were computed for images of mice acquired on a 7T Bruker BioSpec scanner, using a computationally efficient method for solving the Markov Random Field formulation of the multi-point Dixon model. The B0 field maps were processed with a novel hole-filling method, based on edge strength between regions, and a novel k-means method, based on field-map intensities, which were iteratively applied to automatically detect and reinitialize error regions in the B0 field maps. Errors were manually assessed in the B0 field maps and chemical parameter maps both before and after error correction. Results Partial swaps were found in 6% of images when processed with FLAWLESS. After REFINED correction, only 0.7% of images contained partial swaps, resulting in an 88% decrease in error rate. Complete swaps were not problematic. Conclusion Ex post facto error correction is a viable supplement to a priori techniques for producing globally smooth B0 field maps, without partial swaps. With our processing pipeline, it is possible to process image volumes rapidly, robustly, and almost automatically. PMID:23023815

Recovery of chemical estimates by field inhomogeneity neighborhood error detection (REFINED): fat/water separation at 7 tesla.

PubMed

Narayan, Sreenath; Kalhan, Satish C; Wilson, David L

2013-05-01

To reduce swaps in fat-water separation methods, a particular issue on 7 Tesla (T) small animal scanners due to field inhomogeneity, using image postprocessing innovations that detect and correct errors in the B0 field map. Fat-water decompositions and B0 field maps were computed for images of mice acquired on a 7T Bruker BioSpec scanner, using a computationally efficient method for solving the Markov Random Field formulation of the multi-point Dixon model. The B0 field maps were processed with a novel hole-filling method, based on edge strength between regions, and a novel k-means method, based on field-map intensities, which were iteratively applied to automatically detect and reinitialize error regions in the B0 field maps. Errors were manually assessed in the B0 field maps and chemical parameter maps both before and after error correction. Partial swaps were found in 6% of images when processed with FLAWLESS. After REFINED correction, only 0.7% of images contained partial swaps, resulting in an 88% decrease in error rate. Complete swaps were not problematic. Ex post facto error correction is a viable supplement to a priori techniques for producing globally smooth B0 field maps, without partial swaps. With our processing pipeline, it is possible to process image volumes rapidly, robustly, and almost automatically. Copyright © 2012 Wiley Periodicals, Inc.

A generalized framework unifying image registration and respiratory motion models and incorporating image reconstruction, for partial image data or full images.

PubMed

McClelland, Jamie R; Modat, Marc; Arridge, Simon; Grimes, Helen; D'Souza, Derek; Thomas, David; Connell, Dylan O'; Low, Daniel A; Kaza, Evangelia; Collins, David J; Leach, Martin O; Hawkes, David J

2017-06-07

Surrogate-driven respiratory motion models relate the motion of the internal anatomy to easily acquired respiratory surrogate signals, such as the motion of the skin surface. They are usually built by first using image registration to determine the motion from a number of dynamic images, and then fitting a correspondence model relating the motion to the surrogate signals. In this paper we present a generalized framework that unifies the image registration and correspondence model fitting into a single optimization. This allows the use of 'partial' imaging data, such as individual slices, projections, or k-space data, where it would not be possible to determine the motion from an individual frame of data. Motion compensated image reconstruction can also be incorporated using an iterative approach, so that both the motion and a motion-free image can be estimated from the partial image data. The framework has been applied to real 4DCT, Cine CT, multi-slice CT, and multi-slice MR data, as well as simulated datasets from a computer phantom. This includes the use of a super-resolution reconstruction method for the multi-slice MR data. Good results were obtained for all datasets, including quantitative results for the 4DCT and phantom datasets where the ground truth motion was known or could be estimated.

Structural characterisation by both positive- and negative-ion electrospray mass spectrometry of partially methyl-esterified oligogalacturonides purified by semi-preparative high-performance anion-exchange chromatography.

PubMed

Quéméner, Bernard; Désiré, Cédric; Lahaye, Marc; Debrauwer, Laurent; Negroni, Luc

2003-01-01

The off-line coupling of high-performance anion-exchange chromatography (HPAEC) to electrospray ionisation/ion trap mass spectrometry (ESI-ITMS) is described. The Dionex carbohydrate membrane desalter (CMD) has been assessed as an on-line chromatographic desalting system to remove the high sodium concentration necessary for the HPAEC separation of partially methyl-esterified oligogalacturonides. The developed HPAEC configuration proved to be suitable for indirect coupling with ESI-ITMS. This paper provides some interesting features of positive- and negative-ion multistage tandem mass spectrometry (MS(n)) analysis of these acidic oligosaccharides. The spectra acquired in both negative- and positive-ion modes show characteristic fragment ions resulting from glycosidic bond and cross-ring cleavages. Some new mass spectrometric fragmentation routes are also described. The positive-ion mode gave more complex spectra but was as informative as the negative-ion mode. ESI-ITMS was revealed to be, as previously reported from direct use on an unseparated enzymatic digest, a powerful sequencing technique for the determination of linkage type and the methyl ester distribution of partially methyl-esterified oligogalacturonides. Moreover, unlike matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-ToF MS), it gives valuable information on the elution behaviour of these oligomers in relation to their structure, namely the HPAEC co-elution of isomeric structures.

A Measure Approximation for Distributionally Robust PDE-Constrained Optimization Problems

DOE PAGES

Kouri, Drew Philip

2017-12-19

In numerous applications, scientists and engineers acquire varied forms of data that partially characterize the inputs to an underlying physical system. This data is then used to inform decisions such as controls and designs. Consequently, it is critical that the resulting control or design is robust to the inherent uncertainties associated with the unknown probabilistic characterization of the model inputs. Here in this work, we consider optimal control and design problems constrained by partial differential equations with uncertain inputs. We do not assume a known probabilistic model for the inputs, but rather we formulate the problem as a distributionally robustmore » optimization problem where the outer minimization problem determines the control or design, while the inner maximization problem determines the worst-case probability measure that matches desired characteristics of the data. We analyze the inner maximization problem in the space of measures and introduce a novel measure approximation technique, based on the approximation of continuous functions, to discretize the unknown probability measure. Finally, we prove consistency of our approximated min-max problem and conclude with numerical results.« less

UHF Signal Processing and Pattern Recognition of Partial Discharge in Gas-Insulated Switchgear Using Chromatic Methodology

PubMed Central

Wang, Xiaohua; Li, Xi; Rong, Mingzhe; Xie, Dingli; Ding, Dan; Wang, Zhixiang

2017-01-01

The ultra-high frequency (UHF) method is widely used in insulation condition assessment. However, UHF signal processing algorithms are complicated and the size of the result is large, which hinders extracting features and recognizing partial discharge (PD) patterns. This article investigated the chromatic methodology that is novel in PD detection. The principle of chromatic methodologies in color science are introduced. The chromatic processing represents UHF signals sparsely. The UHF signals obtained from PD experiments were processed using chromatic methodology and characterized by three parameters in chromatic space (H, L, and S representing dominant wavelength, signal strength, and saturation, respectively). The features of the UHF signals were studied hierarchically. The results showed that the chromatic parameters were consistent with conventional frequency domain parameters. The global chromatic parameters can be used to distinguish UHF signals acquired by different sensors, and they reveal the propagation properties of the UHF signal in the L-shaped gas-insulated switchgear (GIS). Finally, typical PD defect patterns had been recognized by using novel chromatic parameters in an actual GIS tank and good performance of recognition was achieved. PMID:28106806

UHF Signal Processing and Pattern Recognition of Partial Discharge in Gas-Insulated Switchgear Using Chromatic Methodology.

PubMed

Wang, Xiaohua; Li, Xi; Rong, Mingzhe; Xie, Dingli; Ding, Dan; Wang, Zhixiang

2017-01-18

The ultra-high frequency (UHF) method is widely used in insulation condition assessment. However, UHF signal processing algorithms are complicated and the size of the result is large, which hinders extracting features and recognizing partial discharge (PD) patterns. This article investigated the chromatic methodology that is novel in PD detection. The principle of chromatic methodologies in color science are introduced. The chromatic processing represents UHF signals sparsely. The UHF signals obtained from PD experiments were processed using chromatic methodology and characterized by three parameters in chromatic space ( H , L , and S representing dominant wavelength, signal strength, and saturation, respectively). The features of the UHF signals were studied hierarchically. The results showed that the chromatic parameters were consistent with conventional frequency domain parameters. The global chromatic parameters can be used to distinguish UHF signals acquired by different sensors, and they reveal the propagation properties of the UHF signal in the L-shaped gas-insulated switchgear (GIS). Finally, typical PD defect patterns had been recognized by using novel chromatic parameters in an actual GIS tank and good performance of recognition was achieved.

Partial Least Squares Based Gene Expression Analysis in EBV- Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders.

PubMed

Wu, Sa; Zhang, Xin; Li, Zhi-Ming; Shi, Yan-Xia; Huang, Jia-Jia; Xia, Yi; Yang, Hang; Jiang, Wen-Qi

2013-01-01

Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

Startup and operating characteristics of an external air-lift reflux partial nitritation-ANAMMOX integrative reactor.

PubMed

Li, Xiang; Huang, Yong; Yuan, Yi; Bi, Zhen; Liu, Xin

2017-08-01

The differences in the physiological characteristics between AOB and ANAMMOX bacteria lead to suboptimal performance when used in a single reactor. In this study, aerobic and anaerobic zones with different survival environments were constructed in a single reactor to realize partitioned culture of AOB and ANAMMOX bacteria. An external air-lift reflux system was formed which used the exhaust from the aeration zone as power to return the effluent to the aeration zone. The reflux system effectively alleviated the large pH fluctuations and promoted NO 2 - -N to rapidly use by ANAMMOX bacteria, effectively inhibiting the activity of NOB. After 95d of running, the nitrogen removal rate increased from the initial 0.21kg/(m 3 ·d) to 3.1kg/(m 3 ·d). FISH analyses further demonstrated that AOB and ANAMMOX bacteria acquired efficient enrichment in the corresponding zone. Thus, this type of integrative reactor may create the environments needed for the partial nitritation-ANAMMOX processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of partial nitrification using pulse aeration for treating digested effluent of swine wastewater.

PubMed

Wang, Shuang; Deng, Liangwei; Zheng, Dan; Wang, Lan; Zhang, Yunhong; Yang, Hongnan; Jiang, Yiqi; Huang, Fangyu

2018-04-22

Three sequencing batch reactors (SBRs) were used to investigate the influence of pulse frequencies on the partial nitrification (PN) process in this study. At a total aeration time of 6 min each hour, the aerated frequencies of R1, R2 and R3 were 6, 3 and 2 time h -1 . During the steady period (117-143d), the nitrite accumulation rates (NARs) were 90.80%, 90.71% and 90.23% in R1, R2 and R3, respectively, indicating a steady nitritation was acquired. Activity measurements of the sludge samples taken at day 138 showed the activity of nitrite oxidating bacteria (NOB) was 0, indicating NOBs were successfully suppressed. The ratio of NO 2 - -N to NH 4 + -N in the effluent of R3 was 1.35, which most closely matched the influent of Anammox process. However, the energy efficiency evaluation showed that R1 had the highest actual oxygen transfer efficiency (AOTE) and dynamical efficiency (DE). Copyright © 2018 Elsevier Ltd. All rights reserved.

Pitfalls in 16-detector row CT of the coronary arteries.

PubMed

Nakanishi, Tadashi; Kayashima, Yasuyo; Inoue, Rintaro; Sumii, Kotaro; Gomyo, Yukihiko

2005-01-01

Recently developed 16-detector row computed tomography (CT) has been introduced as a reliable noninvasive imaging modality for evaluating the coronary arteries. In most cases, with appropriate premedication that includes beta-blockers and nitroglycerin, ideal data sets can be acquired from which to obtain excellent-quality coronary CT angiograms, most often with multiplanar reformation, thin-slab maximum intensity projection, and volume rendering. However, various artifacts associated with data creation and reformation, postprocessing methods, and image interpretation can hamper accurate diagnosis. These artifacts can be related to pulsation (nonassessable segments, pseudostenosis) as well as rhythm disorders, respiratory issues, partial volume averaging effect, high-attenuation entities, inappropriate scan pitch, contrast material enhancement, and patient body habitus. Some artifacts have already been resolved with technical advances, whereas others represent partially inherent limitations of coronary CT angiography. Familiarity with the pitfalls of coronary angiography with 16-detector row CT, coupled with the knowledge of both the normal anatomy and anatomic variants of the coronary arteries, can almost always help radiologists avoid interpretive errors in the diagnosis of coronary artery stenosis. (c) RSNA, 2005.

[Implantation of an Artificial Iris in 11 Patients].

PubMed

Kniestedt, C; Eberhard, R; Fleischhauer, J

2016-04-01

Background. Iris defects are mostly acquired after injury, or may be iatrogenic after surgical excision of iris tumours or the result of collateral trauma after anterior segment surgery. They cause severe visual disability, e.g. glare, loss of contrast sensitivity, and loss of best corrected visual acuity. The foldable Koch iris prosthesis has a customised iris design and may be used to reconstruct the anterior segment in patients with partial or complete aniridia. History and Signs. We present the surgical management and clinical course of 6 patients with traumatic iris defects, together with 3 patients with partial aniridia after cataract surgery. Cataract surgery and implantation of an artificial iris were performed in 2 female patients (3 eyes) with congenital aniridia syndrome. Therapy and Outcome. No patient exhibited complications in the postoperative course, with the exception of various intraocular pressure peaks due to secondary glaucoma, that were all corrected by medication to lower topical pressure. Conclusions. In patients with major iris defects, the artificial iris allows functionally and aesthetically satisfactory reconstruction of the anterior segment. Georg Thieme Verlag KG Stuttgart · New York.

Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib.

PubMed

Miyamoto, Shingo; Ikushima, Soichiro; Ono, Ryu; Awano, Nobuyasu; Kondo, Keisuke; Furuhata, Yoshiaki; Fukumoto, Kento; Kumasaka, Toshio

2016-02-01

A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thermal-to-visible face recognition using partial least squares.

PubMed

Hu, Shuowen; Choi, Jonghyun; Chan, Alex L; Schwartz, William Robson

2015-03-01

Although visible face recognition has been an active area of research for several decades, cross-modal face recognition has only been explored by the biometrics community relatively recently. Thermal-to-visible face recognition is one of the most difficult cross-modal face recognition challenges, because of the difference in phenomenology between the thermal and visible imaging modalities. We address the cross-modal recognition problem using a partial least squares (PLS) regression-based approach consisting of preprocessing, feature extraction, and PLS model building. The preprocessing and feature extraction stages are designed to reduce the modality gap between the thermal and visible facial signatures, and facilitate the subsequent one-vs-all PLS-based model building. We incorporate multi-modal information into the PLS model building stage to enhance cross-modal recognition. The performance of the proposed recognition algorithm is evaluated on three challenging datasets containing visible and thermal imagery acquired under different experimental scenarios: time-lapse, physical tasks, mental tasks, and subject-to-camera range. These scenarios represent difficult challenges relevant to real-world applications. We demonstrate that the proposed method performs robustly for the examined scenarios.

Benefits of migration in a partially-migratory tropical ungulate

PubMed Central

2013-01-01

Background Partial migration, where one portion of a population conducts seasonal migrations while the other remains on a single range, is common in wild ungulate populations. However the relative costs and benefits associated with the distinct strategies adopted by coexisting migrant and resident individuals have rarely been investigated. Here we compare the body condition of migrants and residents in a partially migratory population of impalas (Aepyceros melampus) in Zimbabwe. The study was conducted during two consecutive years with highly contrasted population densities (16.4 and 8.6 indiv/km2) due to harvesting. Results We first identify a population substructure with a north–south sub-division in two spatial units related to distinct soils and vegetation cover. Impalas in the north range had a consistently higher diet quality and body condition than those in the south range. At the beginning of the dry season about one third of the individuals migrated from the lower (i.e. south) to the higher (i.e. north) diet quality range. This partial migration pattern was consistent between the consecutive years, and most individuals showed constancy to their moving strategy (migrant or resident). In both years, these migrants had a significantly higher body condition at the end of the dry season than the south residents that remained year-round in the lower diet quality range. Diet quality and body condition of impalas were higher in the year of lower density; however we did not detect any evidence for density-dependence in migration propensity, at the individual or population levels, nor in the benefit associated with migration. Conclusions Our findings provide rare evidence for a significant relationship between body condition and seasonal migration strategy in wild ungulates in relation to a difference in the quality of resources acquired between distinct seasonal ranges. This study also constitutes rare evidence of partial migration in a tropical ungulate population. PMID:24079650

Electro-cutaneous stimulation on the palm elicits referred sensations on intact but not on amputated digits

NASA Astrophysics Data System (ADS)

D'Alonzo, M.; Engels, L. F.; Controzzi, M.; Cipriani, C.

2018-02-01

Objective. Grasping and manipulation control critically depends on tactile feedback. Without this feedback, the ability for fine control of a prosthesis is limited in upper limb amputees. Early studies have shown that non-invasive electro-cutaneous stimulation (ES) can induce referred sensations that are spread to a wider and/or more distant area, with respect to the electrodes. Building on this, we sought to exploit this effect to provide somatotopically matched sensory feedback to people with partial hand (digital) amputations. Approach. For the first time, this work investigated the possibility of inducing referred sensations in the digits by activating the palmar nerves. Specifically, we electrically stimulated 18 sites on the palm of non-amputees to evaluate the effects of sites and stimulation parameters on modality, magnitude, and location of the evoked sensations. We performed similar tests with partial hand amputees by testing those sites that had most consistently elicited referred sensations in non-amputees. Main results. We demonstrated referred sensations in non-amputees from all stimulation sites in one form or another. Specifically, the stimulation of 16 of the 18 sites gave rise to reliable referred sensations. Amputees experienced referred sensations to unimpaired digits, just like non-amputees, but we were unable to evoke referred sensations in their missing digits: none of them reported sensations that extended beyond the tip of the stump. Significance. The possibility of eliciting referred sensations on the digits may be exploited in haptic systems for providing touch sensations without obstructing the fingertips or their movements. The study also suggests that the phenomenon of referred sensations through ES may not be exploited for partial hand prostheses, and it invites researchers to explore alternative approaches. Finally, the results seem to confirm previous studies suggesting that the stumps in partial hand amputees partially acquire the role of the missing fingertips, physiologically and cognitively.

Near infrared spectroscopy of human muscles

NASA Astrophysics Data System (ADS)

Gasbarrone, R.; Currà, A.; Cardillo, A.; Bonifazi, G.; Serranti, S.

2018-02-01

Optical spectroscopy is a powerful tool in research and industrial applications. Its properties of being rapid, non-invasive and not destructive make it a promising technique for qualitative as well as quantitative analysis in medicine. Recent advances in materials and fabrication techniques provided portable, performant, sensing spectrometers readily operated by user-friendly cabled or wireless systems. We used such a system to test whether infrared spectroscopy techniques, currently utilized in many areas as primary/secondary raw materials sector, cultural heritage, agricultural/food industry, environmental remote and proximal sensing, pharmaceutical industry, etc., could be applied in living humans to categorize muscles. We acquired muscles infrared spectra in the Vis-SWIR regions (350-2500 nm), utilizing an ASD FieldSpec 4 Standard-Res Spectroradiometer with a spectral sampling capability of 1.4 nm at 350-1000 nm and 1.1 nm at 1001-2500 nm. After a preliminary spectra pre-processing (i.e. signal scattering reduction), Principal Component Analysis (PCA) was applied to identify similar spectral features presence and to realize their further grouping. Partial Least-Squares Discriminant Analysis (PLS-DA) was utilized to implement discrimination/prediction models. We studied 22 healthy subjects (age 25-89 years, 11 females), by acquiring Vis-SWIR spectra from the upper limb muscles (i.e. biceps, a forearm flexor, and triceps, a forearm extensor). Spectroscopy was performed in fixed limb postures (elbow angle approximately 90‡). We found that optical spectroscopy can be applied to study human tissues in vivo. Vis-SWIR spectra acquired from the arm detect muscles, distinguish flexors from extensors.

Monitoring the turbidity and surface temperature changes and effects of the 17 August 1999 earthquake in the Izmit Gulf, Turkey by the Landsat TM/ETM data.

PubMed

Tüfekçi, Kenan; Akman, A Unal

2005-09-01

The temporal turbidity and surface temperature changes and effects of the 17 August 1999 earthquake in the Izmit Gulf, Turkey have been investigated using Landsat TM/ETM data. The gulf is in the Mediterranean-Black Sea transition climatic zone and is partially surrounded by green vegetation cover and degraded and densely urbanized-industrialized areas. Landsat TM/ETM data acquired in 1990-1999 confirms increase in turbidity. Turbidity is always low in the southern part and high in the northern part of the gulf, because the more urbanized and industrialized areas are located in the northern part. The Landsat-7 ETM data acquired in the same year (1999) shows seasonal changes in turbidity. Moreover, the two high turbidity and surface temperature anomalies, one of which is parallel to the 17 August 1999 earthquake surface rupture (east-west) and the other which is in the northwest-southeast direction were mapped from Landsat-5 TM data acquired the day (18.08.1999) following the earthquake in the east end of the gulf. On the basis of turbidity implying the sea bottom movement, it is possible to state that a second rupture in the northwest and southeast direction could have occurred at the sea bottom during the earthquake. The distribution of the seismicity centers and the orientation of the lineaments in the area support this finding.

Characterization of the gag/fusion protein encoded by the defective Duplan retrovirus inducing murine acquired immunodeficiency syndrome.

PubMed Central

Huang, M; Jolicoeur, P

1990-01-01

Murine acquired immunodeficiency syndrome is induced by a defective retrovirus. Sequencing of this defective viral genome revealed a long open reading frame which encodes a putative gag/fusion protein, N-MA-p12-CA-NC-COOH, (D. C. Aziz, Z. Hanna, and P. Jolicoeur, Nature (London) 338:505-508, 1989). We raised a specific antibody to the unique p12 domain of this gag fusion precursor, Pr60gag. We found that Pr60gag was indeed encoded by the defective viral genome both in cell-free translation reticulocyte extracts and in infected mouse fibroblasts. Pr60gag was found to be myristylated, phosphorylated, and attached to the cell membrane, like other helper murine leukemia virus (MuLV) gag precursors. Pr60gag was not substantially cleaved within the nonproducer cells and was not released from these cells. However, in the presence of helper MuLV proteins, it formed phenotypically mixed particles. In these particles, Pr60gag was only partially cleaved. In helper MuLV-producing cells harboring the defective virus, a gag-related p40 intermediate was generated both intracellularly and extracellularly. In these cells, Pr60gag appeared to behave as a dominant negative mutant, interfering with proper cleavage of helper Pr65gag. Our data indicate that Pr60gag is a major (and possibly the only) gene product of the defective murine acquired immunodeficiency syndrome virus and is likely to harbor some determinants of pathogenicity of this virus. Images PMID:2243376

Ontogeny of Foraging Competence in Capuchin Monkeys (Cebus capucinus) for Easy versus Difficult to Acquire Fruits: A Test of the Needing to Learn Hypothesis.

PubMed

Eadie, Elizabeth Christine

2015-01-01

Which factors select for long juvenile periods in some species is not well understood. One potential reason to delay the onset of reproduction is slow food acquisition rates, either due to competition (part of the ecological risk avoidance hypothesis), or due to a decreased foraging efficiency (a version of the needing to learn hypothesis). Capuchins provide a useful genus to test the needing to learn hypothesis because they are known for having long juvenile periods and a difficult-to-acquire diet. Generalized, linear, mixed models with data from 609 fruit forage focal follows on 49, habituated, wild Cebus capucinus were used to test two predictions from the needing-to-learn hypothesis as it applies to fruit foraging skills: 1) capuchin monkeys do not achieve adult foraging return rates for difficult-to-acquire fruits before late in the juvenile period; and 2) variance in return rates for these fruits is at least partially associated with differences in foraging skill. In support of the first prediction, adults, compared with all younger age classes, had significantly higher foraging return rates when foraging for fruits that were ranked as difficult-to-acquire (return rates relative to adults: 0.30-0.41, p-value range 0.008-0.016), indicating that the individuals in the group who have the most foraging experience also achieve the highest return rates. In contrast, and in support of the second prediction, there were no significant differences between age classes for fruits that were ranked as easy to acquire (return rates relative to adults: 0.97-1.42, p-value range 0.086-0.896), indicating that strength and/or skill are likely to affect return rates. In addition, fruits that were difficult to acquire were foraged at nearly identical rates by adult males and significantly smaller (and presumably weaker) adult females (males relative to females: 1.01, p = 0.978), while subadult females had much lower foraging efficiency than the similarly-sized but more experienced adult females (subadults relative to adults: 0.34, p = 0.052), indicating that skill, specifically, is likely to have an effect on return rates. These results are consistent with the needing to learn hypothesis and indicate that long juvenile periods in capuchins may be the result of selection for more time to learn foraging skills for difficult-to-acquire fruits.

Multi-probe-based resonance-frequency electrical impedance spectroscopy for detection of suspicious breast lesions: improving performance using partial ROC optimization

NASA Astrophysics Data System (ADS)

Lederman, Dror; Zheng, Bin; Wang, Xingwei; Wang, Xiao Hui; Gur, David

2011-03-01

We have developed a multi-probe resonance-frequency electrical impedance spectroscope (REIS) system to detect breast abnormalities. Based on assessing asymmetry in REIS signals acquired between left and right breasts, we developed several machine learning classifiers to classify younger women (i.e., under 50YO) into two groups of having high and low risk for developing breast cancer. In this study, we investigated a new method to optimize performance based on the area under a selected partial receiver operating characteristic (ROC) curve when optimizing an artificial neural network (ANN), and tested whether it could improve classification performance. From an ongoing prospective study, we selected a dataset of 174 cases for whom we have both REIS signals and diagnostic status verification. The dataset includes 66 "positive" cases recommended for biopsy due to detection of highly suspicious breast lesions and 108 "negative" cases determined by imaging based examinations. A set of REIS-based feature differences, extracted from the two breasts using a mirror-matched approach, was computed and constituted an initial feature pool. Using a leave-one-case-out cross-validation method, we applied a genetic algorithm (GA) to train the ANN with an optimal subset of features. Two optimization criteria were separately used in GA optimization, namely the area under the entire ROC curve (AUC) and the partial area under the ROC curve, up to a predetermined threshold (i.e., 90% specificity). The results showed that although the ANN optimized using the entire AUC yielded higher overall performance (AUC = 0.83 versus 0.76), the ANN optimized using the partial ROC area criterion achieved substantially higher operational performance (i.e., increasing sensitivity level from 28% to 48% at 95% specificity and/ or from 48% to 58% at 90% specificity).

First report of cavitary pneumonia due to community-acquired Acinetobacter pittii, study of virulence and overview of pathogenesis and treatment.

PubMed

Larcher, Romaric; Pantel, Alix; Arnaud, Erik; Sotto, Albert; Lavigne, Jean-Philippe

2017-07-06

Acinetobacter pittii is a nosocomial pathogen rarely involved in community-acquired infections. We report for the first time that A. pittii can be responsible for cavitary community-acquired pneumonia and study its virulence, and discuss its pathogenesis and treatment options. A 45-year-old woman with a history of smoking and systemic lupus was admitted to Nimes University Hospital (France) with coughing and sputum lasting for three weeks. Thoracic CT scanner showed cavitary pneumonia. Broncho-alveolar lavage cultures found community-acquired Acinetobacter calcoaceticus-baumannii complex. The clinical outcome was favourable after twenty-one days of antimicrobial treatment by piperacillin/tazobactam and amikacin then cefepime. Multilocus sequence typing (MLST) analyses identified an A. pittii ST249. Despite the atypical clinical presentation with an unexpected partial destruction of lung parenchyma, we found very low virulence potential of the A. pittii strain with nematode killing assays and biofilm formation test. The median time required to kill 50% of the nematodes was 7 ± 0.3 days for A. pittii ST249, 7 ± 0.2 days for A. baumanii NAB ST2 and 8 ± 0.2 days for E. coli OP50, (p > 0,05). A. pittii ST249 showed significantly slower biofilm formation than A. baumanii NAB ST2: BFI = 8.83 ± 0.59 vs 3.93 ± 0.27 at 2 h (p < 0.0001), BFI = 6.3 ± 0.17 vs 1.87 ± 0.12 at 3 h (p < 0.0001) and BFI = 3.67 ± 0.41 vs 1.7 ± 0.06 after 4 h of incubation (p < 0.01). Community-acquired A. pittii should be considered as possible cause of sub-acute cavitary pneumonia particularly in a smoking and/or immunocompromised patient despite its low virulence potential.

A prospective, randomized comparison of an in-line heat moisture exchange filter and heated wire humidifiers: rates of ventilator-associated early-onset (community-acquired) or late-onset (hospital-acquired) pneumonia and incidence of endotracheal tube occlusion.

PubMed

Kirton, O C; DeHaven, B; Morgan, J; Morejon, O; Civetta, J

1997-10-01

To compare the performance of an in-line heat moisture exchanging filter (HMEF) (Pall BB-100; Pall Corporation; East Hills, NY) to a conventional heated wire humidifier (H-wH) (Marquest Medical Products Inc., Englewood, Colo) in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia (VAP) and the rate of endotracheal tube occlusion. This report describes a prospective, randomized trial of 280 consecutive trauma patients in a 20-bed trauma ICU (TICU). All intubated patients not ventilated elsewhere in the medical center prior to their TICU admission were randomized to either an in-line HMEF or a H-wH in the breathing circuit. Ventilator circuits were changed routinely every 7 days, and closed system suction catheters were changed every 3 days. HMEFs were changed every 24 h, or more frequently if necessary. A specific endotracheal tube suction and lavage protocol was not employed. Patients were dropped from the HMEF group if the filter was changed more than three times a day or the patient was placed on a regimen of ultra high-frequency ventilation. The Centers for Disease Control and Prevention (CDC) criteria for diagnosis of pneumonia were used; early-onset, community-acquired pneumonia was defined if CDC criteria were met in < or =3 days, and late-onset, hospital-acquired pneumonia was defined if criteria were met in >3 days. Laboratory and chest radiograph interpretation were blinded. The patient ages ranged from 15 to 95 years in the HMEF group and 16 to 87 years in the H-wH group (p=not significant), with a mean age of 46 years and 48 years, respectively. The male to female ratio ranged between 78 to 82%/22 to 18%, respectively, and 55% of all admissions were related to blunt trauma, 40% secondary to penetrating trauma, and 5% to major burns. There was no difference in Injury Severity Score (ISS) between the two groups. Moreover, there was no significant difference in mean ISS among those who did not develop pneumonia and those patients who developed either early-onset, community-acquired or late-onset, hospital-acquired pneumonia. The HMEF nosocomial VAP rate was 6% compared to 16% for the H-wH group (p<0.05), and total ventilator circuit costs (per group) were reduced. There were no differences in duration of ventilation (mean+/-SD) if the patient did not develop pneumonia or if the patient developed an early-onset, community-acquired or a late-onset, hospital-acquired pneumonia. Moreover, total TICU days were reduced in the HMEF group. In addition, the incidence of partial endotracheal tube occlusion was not significantly different between the H-wH and the HMEF groups. The HMEF used in this study reduced the incidence of late-onset, hospital-acquired VAP, but not early-onset, community-acquired VAP, compared to the conventional H-wH circuit. This was associated with a significant reduction in total ICU stay. Disposable ventilator circuit costs in the HMEF group were reduced compared to the H-wH group in whom circuit changes occurred at 7-day intervals. The use of the HMEF is a cost-effective clinical practice associated with fewer late-onset, hospital-acquired VAPs, and should result in improved resource allocation and utilization.

Colville Confederated Tribes' Performance Project Wildlife Mitigation Acquisitions, Annual Report 2006.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitney, Richard; Berger, Matthew; Tonasket, Patrick

2006-12-01

The Colville Confederated Tribes Wildlife Mitigation Project is protecting lands as partial mitigation for hydropower's share of the wildlife losses resulting from Chief Joseph and Grand Coulee Dams. The Mitigation Project protects and manages 54,606 acres for the biological requirements of managed wildlife species that are important to the Colville Tribes. With the inclusion of 2006 acquisitions, the Colville Tribes have acquired approximately 32,018 habitat units (HUs) towards a total 35,819 HUs lost from original inundation due to hydropower development. This annual report for 2006 briefly describes that four priority land acquisitions that were considered for enrollment into the Colvillemore » Tribes Mitigation Project during the 2006 contract period.« less

Plexiform schwannoma: an unusual clitoral mass.

PubMed

Sammarco, Anne G; Abualnadi, Noor M; Andraska, Elizabeth A; Tracy, Paige V; Berger, Mitchell B; Haefner, Hope K

2017-03-01

Acquired clitoral enlargement is a rare condition resulting from a variety of etiologies, including tumors and excess androgens. Few cases of nonmalignant schwannoma, a benign tumor of the peripheral nerve sheath, have been reported in the literature as causes of clitoral enlargement in patients without known neurofibromatosis. These painless, slow-growing tumors rarely recur once excised. We present the initial investigation of a patient with a large clitoral schwannoma and subsequent treatment with partial vulvectomy. The workup, including advanced pelvic imaging for diagnosis and surgical planning, as well as removal of the clitoral tumor with preservation of functional tissue and restoration of normal vulvar anatomy despite a large excision, is demonstrated. Copyright © 2016 Elsevier Inc. All rights reserved.

Gait rehabilitation with a high tech platform based on virtual reality conveys improvements in walking ability of children suffering from acquired brain injury.

PubMed

Biffi, E; Beretta, E; Diella, E; Panzeri, D; Maghini, C; Turconi, A C; Strazzer, S; Reni, G

2015-01-01

The Gait Real-time Analysis Interactive Lab (GRAIL) is an instrumented multi-sensor platform based on immersive virtual reality for gait training and rehabilitation. Few studies have been included GRAIL to evaluate gait patterns in normal and disabled people and to improve gait in adults, while at our knowledge no evidence on its use for the rehabilitation of children is available. In this study, 4 children suffering from acquired brain injury (ABI) underwent a 5 session treatment with GRAIL, to improve walking and balance ability in engaging VR environments. The first and the last sessions were partially dedicated to gait evaluation. Results are promising: improvements were recorded at the ankle level, selectively at the affected side, and at the pelvic level, while small changes were measured at the hip and knee joints, which were already comparable to healthy subjects. All these changes also conveyed advances in the symmetry of the walking pattern. In the next future, a longer intervention will be proposed and more children will be enrolled to strongly prove the effectiveness of GRAIL in the rehabilitation of children with ABI.

Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

PubMed

Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

2016-01-01

Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways

PubMed Central

Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

2016-01-01

Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process. PMID:27904686

The singing power ratio as an objective measure of singing voice quality in untrained talented and nontalented singers.

PubMed

Watts, Christopher; Barnes-Burroughs, Kathryn; Estis, Julie; Blanton, Debra

2006-03-01

A growing body of contemporary research has investigated differences between trained and untrained singing voices. However, few studies have separated untrained singers into those who do and do not express abilities related to singing talent, including accurate pitch control and production of a pleasant timbre (voice quality). This investigation studied measures of the singing power ratio (SPR), which is a quantitative measure of the resonant quality of the singing voice. SPR reflects the amplification or suppression in the vocal tract of the harmonics produced by the sound source. This measure was acquired from the voices of untrained talented and nontalented singers as a means to objectively investigate voice quality differences. Measures of SPR were acquired from vocal samples with fast Fourier transform (FFT) power spectra to analyze the amplitude level of the partials in the acoustic spectrum. Long-term average spectra (LTAS) were also analyzed. Results indicated significant differences in SPR between groups, which suggest that vocal tract resonance, and its effect on perceived vocal timbre or quality, may be an important variable related to the perception of singing talent. LTAS confirmed group differences in the tuning of vocal tract harmonics.

Deletion of the long arm of chromosome 20 (del(20)(q11)) in myeloid disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Testa, J.R.; Kinnealey, A.; Rowley, J.D.

1978-11-01

Detailed clinical and cytogenetic studies were performed in five patients who had abnormal hematopoiesis and an acquired deletion of an F-group chromosome. Cytogenetic analyses, with banding techniques, of cells from bone marrow, spleen, or unstimulated peripheral blood showed a partial deletion of the long arm of one chromosome 20 (del(20)(q11)) in all five patients. Three patients had myeloproliferative disorders of uncertain classification, the fourth had possible preleukemia, and the fifth had acute myelomonocytic leukemia. Although the five cases showed certain similarities, the clinical and hematologic findings seen with the 20q- abnormality were not specific. None of the patients showed evidencemore » of polycythemia vera or idiopathic acquired refractory sideroblastic anemia, two diseases previously associated with the 20q-. Our studies indicate that the 20q-abnormality is not limited to diseases primarily affecting erythropoiesis but that it can be found in the broader spectrum of myeloid disorders. In polycythemia vera, the 20q- has sometimes been regarded as a possible result of previous therapy with cytotoxic agents; however, four of our patients were untreated when the deletion was first noted.« less

Acoustic Measurements of a Large Civil Transport Main Landing Gear Model

NASA Technical Reports Server (NTRS)

Ravetta, Patricio A.; Khorrami, Mehdi R.; Burdisso, Ricardo A.; Wisda, David M.

2016-01-01

Microphone phased array acoustic measurements of a 26 percent-scale, Boeing 777-200 main landing gear model with and without noise reduction fairings installed were obtained in the anechoic configuration of the Virginia Tech Stability Tunnel. Data were acquired at Mach numbers of 0.12, 0.15, and 0.17 with the latter speed used as the nominal test condition. The fully and partially dressed gear with the truck angle set at 13 degrees toe-up landing configuration were the two most extensively tested configurations, serving as the baselines for comparison purposes. Acoustic measurements were also acquired for the same two baseline configurations with the truck angle set at 0 degrees. In addition, a previously tested noise reducing, toboggan-shaped fairing was re-evaluated extensively to address some of the lingering questions regarding the extent of acoustic benefit achievable with this device. The integrated spectra generated from the acoustic source maps reconfirm, in general terms, the previously reported noise reduction performance of the toboggan fairing as installed on an isolated gear. With the recent improvements to the Virginia Tech tunnel acoustic quality and microphone array capabilities, the present measurements provide an additional, higher quality database to the acoustic information available for this gear model.

Application of phase consistency to improve time efficiency and image quality in dual echo black-blood carotid angiography.

PubMed

Kholmovski, Eugene G; Parker, Dennis L

2005-07-01

There is a considerable similarity between proton density-weighted (PDw) and T2-weighted (T2w) images acquired by dual echo fast spin-echo (FSE) sequences. The similarity manifests itself not only in image space as correspondence between intensities of PDw and T2w images, but also in phase space as consistency between phases of PDw and T2w images. Methods for improving the imaging efficiency and image quality of dual echo FSE sequences based on this feature have been developed. The total scan time of dual echo FSE acquisition may be reduced by as much as 25% by incorporating an estimate of the image phase from a fully sampled PDw image when reconstructing partially sampled T2w images. The quality of T2w images acquired using phased array coils may be significantly improved by using the developed noise reduction reconstruction scheme, which is based on the correspondence between the PDw and T2w image intensities and the consistency between the PDw and T2w image phases. Studies of phantom and human subject MRI data were performed to evaluate the effectiveness of the techniques.

Limited Transfer of Newly Acquired Movement Patterns across Walking and Running in Humans

PubMed Central

Ogawa, Tetsuya; Kawashima, Noritaka; Ogata, Toru; Nakazawa, Kimitaka

2012-01-01

The two major modes of locomotion in humans, walking and running, may be regarded as a function of different speed (walking as slower and running as faster). Recent results using motor learning tasks in humans, as well as more direct evidence from animal models, advocate for independence in the neural control mechanisms underlying different locomotion tasks. In the current study, we investigated the possible independence of the neural mechanisms underlying human walking and running. Subjects were tested on a split-belt treadmill and adapted to walking or running on an asymmetrically driven treadmill surface. Despite the acquisition of asymmetrical movement patterns in the respective modes, the emergence of asymmetrical movement patterns in the subsequent trials was evident only within the same modes (walking after learning to walk and running after learning to run) and only partial in the opposite modes (walking after learning to run and running after learning to walk) (thus transferred only limitedly across the modes). Further, the storage of the acquired movement pattern in each mode was maintained independently of the opposite mode. Combined, these results provide indirect evidence for independence in the neural control mechanisms underlying the two locomotive modes. PMID:23029490

Application of Near Infrared Reflectance Spectroscopy for Rapid and Non-Destructive Discrimination of Hulled Barley, Naked Barley, and Wheat Contaminated with Fusarium

PubMed Central

Lim, Jongguk; Kim, Giyoung; Mo, Changyeun; Oh, Kyoungmin; Kim, Geonseob; Ham, Hyeonheui; Kim, Seongmin; Kim, Moon S.

2018-01-01

Fusarium is a common fungal disease in grains that reduces the yield of barley and wheat. In this study, a near infrared reflectance spectroscopic technique was used with a statistical prediction model to rapidly and non-destructively discriminate grain samples contaminated with Fusarium. Reflectance spectra were acquired from hulled barley, naked barley, and wheat samples contaminated with Fusarium using near infrared reflectance (NIR) spectroscopy with a wavelength range of 1175–2170 nm. After measurement, the samples were cultured in a medium to discriminate contaminated samples. A partial least square discrimination analysis (PLS-DA) prediction model was developed using the acquired reflectance spectra and the culture results. The correct classification rate (CCR) of Fusarium for the hulled barley, naked barley, and wheat samples developed using raw spectra was 98% or higher. The accuracy of discrimination prediction improved when second and third-order derivative pretreatments were applied. The grains contaminated with Fusarium could be rapidly discriminated using spectroscopy technology and a PLS-DA discrimination model, and the potential of the non-destructive discrimination method could be verified. PMID:29301319

Acquired Immunological Tolerance to a Fraction of Bovine Gamma Globulin

PubMed Central

Dresser, D. W.

1961-01-01

A state of acquired immunological tolerance to bovine gamma globulin (BGG) has been observed in CBA mice injected with 10 mg. BGG within 12 hours of birth. Tolerance was demonstrated by a lack of immune elimination of 131I labelled BGG (BGG-131I) after prior challenge with Freund's adjuvant containing BGG. The degree of tolerance was found to diminish when the time between the tolerance injection and the challenge injection with adjuvant was increased. Mice were found to be tolerant 4 months after injection of 10 mg. BGG at birth but other similarly treated mice were found to be partially immune when challenged 6 months after the tolerance injection. This diminution of tolerance could be prevented by injections of antigen into adult mice whilst they were still tolerant. Precipitin and haemagglutination tests showed that antibody to BGG was present in mice shown to be tolerant to BGG by the antigen-elimination technique. The Ouchterlony double-diffusion technique showed that the mice were tolerant to one fraction of BGG but immune to at least one other fraction. The tolerated fraction of BGG was identified by means of starch-gel electrophoresis. ImagesFIG. 2 PMID:13724353

Single-shot EPI with Nyquist ghost compensation: Interleaved Dual-Echo with Acceleration (IDEA) EPI

PubMed Central

Poser, Benedikt A; Barth, Markus; Goa, Pål-Erik; Deng, Weiran; Stenger, V Andrew

2012-01-01

Echo planar imaging is most commonly used for BOLD fMRI, owing to its sensitivity and acquisition speed. A major problem with EPI is Nyquist (N/2) ghosting, most notably at high field. EPI data are acquired under an oscillating readout gradient and hence vulnerable to gradient imperfections such as eddy current delays and off-resonance effects, as these cause inconsistencies between odd and even k-space lines after time reversal. We propose a straightforward and pragmatic method herein termed Interleaved Dual Echo with Acceleration (IDEA) EPI: Two k-spaces (echoes) are acquired under the positive and negative readout lobes, respectively, by performing phase blips only before alternate readout gradients. From these two k-spaces, two almost entirely ghost free images per shot can be constructed, without need for phase correction. The doubled echo train length can be compensated by parallel imaging and/or partial Fourier acquisition. The two k-spaces can either be complex-averaged during reconstruction, which results in near-perfect cancellation of residual phase errors, or reconstructed into separate images. We demonstrate the efficacy of IDEA EPI and show phantom and in vivo images at both 3 and 7 Tesla. PMID:22411762

Supersonic Flight Dynamics Test: Trajectory, Atmosphere, and Aerodynamics Reconstruction

NASA Technical Reports Server (NTRS)

Kutty, Prasad; Karlgaard, Christopher D.; Blood, Eric M.; O'Farrell, Clara; Ginn, Jason M.; Shoenenberger, Mark; Dutta, Soumyo

2015-01-01

The Supersonic Flight Dynamics Test is a full-scale flight test of a Supersonic Inflatable Aerodynamic Decelerator, which is part of the Low Density Supersonic Decelerator technology development project. The purpose of the project is to develop and mature aerodynamic decelerator technologies for landing large mass payloads on the surface of Mars. The technologies include a Supersonic Inflatable Aerodynamic Decelerator and Supersonic Parachutes. The first Supersonic Flight Dynamics Test occurred on June 28th, 2014 at the Pacific Missile Range Facility. This test was used to validate the test architecture for future missions. The flight was a success and, in addition, was able to acquire data on the aerodynamic performance of the supersonic inflatable decelerator. This paper describes the instrumentation, analysis techniques, and acquired flight test data utilized to reconstruct the vehicle trajectory, atmosphere, and aerodynamics. The results of the reconstruction show significantly higher lofting of the trajectory, which can partially be explained by off-nominal booster motor performance. The reconstructed vehicle force and moment coefficients fall well within pre-flight predictions. A parameter identification analysis indicates that the vehicle displayed greater aerodynamic static stability than seen in pre-flight computational predictions and ballistic range tests.

Dynamic CT myocardial perfusion imaging: detection of ischemia in a porcine model with FFR verification

NASA Astrophysics Data System (ADS)

Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

2014-03-01

Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.

An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.

PubMed

Hanker, Ariella B; Brewer, Monica Red; Sheehan, Jonathan H; Koch, James P; Sliwoski, Gregory R; Nagy, Rebecca; Lanman, Richard; Berger, Michael F; Hyman, David M; Solit, David B; He, Jie; Miller, Vincent; Cutler, Richard E; Lalani, Alshad S; Cross, Darren; Lovly, Christine M; Meiler, Jens; Arteaga, Carlos L

2017-06-01

We report a HER2 T798I gatekeeper mutation in a patient with HER2 L869R -mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2 L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3 E928G , also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2 T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2 T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2 L869R but not HER2 L869R/T798I In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2 L869R/T798I -induced signaling and cell growth. Acquisition of HER2 T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2 L869R is a driver mutation. HER2 T798I -mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib. Significance: We found an acquired HER2 gatekeeper mutation in a patient with HER2 -mutant breast cancer upon clinical progression on neratinib. We speculate that HER2 T798I may arise as a secondary mutation following response to effective HER2 tyrosine kinase inhibitors (TKI) in other cancers with HER2 -activating mutations. This resistance may be overcome by other irreversible HER2 TKIs, such as afatinib. Cancer Discov; 7(6); 575-85. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

PubMed

Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

2007-01-01

Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

Transform- and multi-domain deep learning for single-frame rapid autofocusing in whole slide imaging.

PubMed

Jiang, Shaowei; Liao, Jun; Bian, Zichao; Guo, Kaikai; Zhang, Yongbing; Zheng, Guoan

2018-04-01

A whole slide imaging (WSI) system has recently been approved for primary diagnostic use in the US. The image quality and system throughput of WSI is largely determined by the autofocusing process. Traditional approaches acquire multiple images along the optical axis and maximize a figure of merit for autofocusing. Here we explore the use of deep convolution neural networks (CNNs) to predict the focal position of the acquired image without axial scanning. We investigate the autofocusing performance with three illumination settings: incoherent Kohler illumination, partially coherent illumination with two plane waves, and one-plane-wave illumination. We acquire ~130,000 images with different defocus distances as the training data set. Different defocus distances lead to different spatial features of the captured images. However, solely relying on the spatial information leads to a relatively bad performance of the autofocusing process. It is better to extract defocus features from transform domains of the acquired image. For incoherent illumination, the Fourier cutoff frequency is directly related to the defocus distance. Similarly, autocorrelation peaks are directly related to the defocus distance for two-plane-wave illumination. In our implementation, we use the spatial image, the Fourier spectrum, the autocorrelation of the spatial image, and combinations thereof as the inputs for the CNNs. We show that the information from the transform domains can improve the performance and robustness of the autofocusing process. The resulting focusing error is ~0.5 µm, which is within the 0.8-µm depth-of-field range. The reported approach requires little hardware modification for conventional WSI systems and the images can be captured on the fly without focus map surveying. It may find applications in WSI and time-lapse microscopy. The transform- and multi-domain approaches may also provide new insights for developing microscopy-related deep-learning networks. We have made our training and testing data set (~12 GB) open-source for the broad research community.

Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.

PubMed

Federico, Lorenzo; Yang, Liping; Brandon, Jason; Panchatcharam, Manikandan; Ren, Hongmei; Mueller, Paul; Sunkara, Manjula; Escalante-Alcalde, Diana; Morris, Andrew J; Smyth, Susan S

2018-01-01

Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted ceramide and sphingomyelin accumulation during diet-induced adipose tissue expansion, accumulation of the LPP3 substrate sphingosine 1- phosphate, and reduced expression of serine palmitoyl transferase. However, adiposity was unaffected by LPP3 deficiency on standard, high fat diet or Western diets, although Western diet-fed mice with adipocyte LPP3 deficiency exhibited improved glucose tolerance. Our results demonstrate functional compartmentalization of lipid phosphatase activity in adipocytes and identify an unexpected role for LPP3 in the regulation of diet-dependent sphingolipid synthesis that may impact on insulin signaling.

A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy.

PubMed

Zazo Seco, Celia; Castells-Nobau, Anna; Joo, Seol-Hee; Schraders, Margit; Foo, Jia Nee; van der Voet, Monique; Velan, S Sendhil; Nijhof, Bonnie; Oostrik, Jaap; de Vrieze, Erik; Katana, Radoslaw; Mansoor, Atika; Huynen, Martijn; Szklarczyk, Radek; Oti, Martin; Tranebjærg, Lisbeth; van Wijk, Erwin; Scheffer-de Gooyert, Jolanda M; Siddique, Saadat; Baets, Jonathan; de Jonghe, Peter; Kazmi, Syed Ali Raza; Sadananthan, Suresh Anand; van de Warrenburg, Bart P; Khor, Chiea Chuen; Göpfert, Martin C; Qamar, Raheel; Schenck, Annette; Kremer, Hannie; Siddiqi, Saima

2017-02-01

A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2. © 2017. Published by The Company of Biologists Ltd.

Improvements in Vertebral-Column Angles and Psychological Metrics After Abdominoplasty With Rectus Plication.

PubMed

Temel, Metin; Türkmen, Arif; Berberoğlu, Ömer

2016-05-01

Substantial fluctuations in body weight can result in diastasis recti and weakening of the connections between the lateral abdominal muscles and the rectus sheath. The authors sought to determine the postural and psychological effects of abdominoplasty with vertical rectus plication. Forty women with substantial back and lumbar pain owing to abdominal lipodystrophy were evaluated in a prospective study. Preoperatively and 6 months postoperatively, patients underwent bidirectional radiography of the thoracic and lumbar regions. A visual analog scale (VAS), the Beck Depression Inventory (BDI), and the Nottingham Health Profile (NHP) were applied to assess physical, psychological, and quality-of-life changes following surgery. Significant improvements in posture, assessed in terms of lumbar lordosis, thoracic kyphosis, and the lumbosacral angle, were observed 6 months after abdominoplasty with rectus plication. Results of the VAS and BDI indicated significant improvements in pain and quality of life, respectively. Results of the NHP indicated significant postoperative improvements in fatigue, pain, and sleep. Abdominoplasty with rectus plication improves posture by tightening the thoracolumbar fascia. In selected patients, abdominoplasty can reduce back and lumbar pain, thereby improving quality of life. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Secondary hypertriglyceridemia in children and adolescents.

PubMed

Blackett, Piers R; Wilson, Don P; McNeal, Catherine J

2015-01-01

Secondary dyslipidemia with predominant hypertriglyceridemia may occur as a consequence of both common and rare causes. After accounting for obesity and associated insulin resistance, clinicians should carefully consider other contributing factors and conditions. Genetic background and causative factors prevail during gestation, infancy, and childhood and continue in adults. Elevations in triglyceride (TG) are associated with transfer of TG to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) resulting in lipolysis, HDL degradation, and formation of atherogenic LDL particles. Defining and treating the underlying cause is the first step toward restoring the lipids and lipoproteins to normal, especially in cases with severe hypertriglyceridemia, who are at risk for acute pancreatitis. Disorders involving the liver, kidney, endocrine, and immune systems and medications need to be considered. Rare diseases such as lipodystrophy and glycogen storage disease are particularly challenging, and there have been promising new developments. Treatment depends on the severity; prevention of acute pancreatitis being a priority in severe cases and lifestyle modification being a foundation for general management followed by targeting TG and predictors of coronary artery disease such as LDL cholesterol and non-HDL cholesterol, when they exceed cutpoints. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance.

PubMed

McCallum, Fiona J; Persson, Kristina E M; Fowkes, Freya J I; Reiling, Linda; Mugyenyi, Cleopatra K; Richards, Jack S; Simpson, Julie A; Williams, Thomas N; Gilson, Paul R; Hodder, Anthony N; Sanders, Paul R; Anders, Robin F; Narum, David L; Chitnis, Chetan; Crabb, Brendan S; Marsh, Kevin; Beeson, James G

2017-04-01

Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen-specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen-specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance. © Society for Leukocyte Biology.

Orthographic learning and self-teaching in a bilingual and biliterate context.

PubMed

Schwartz, Mila; Kahn-Horwitz, Janina; Share, David L

2014-01-01

The aim of this study was to examine self-teaching in the context of English as a foreign language literacy acquisition. Three groups comprising 88 sixth-grade children participated. The first group consisted of Russian-Hebrew-speaking bilinguals who had acquired basic reading skills in Russian as their first language (L1) and literacy and who were literate in Hebrew as a second language. The second group consisted of Russian-Hebrew-speaking bilinguals who had not learned to read in their native Russian but had acquired Hebrew as their first literate language. The third group consisted of Hebrew-speaking monolingual children who were literate in Hebrew. This design facilitated examining the effect of biliteracy and bilingualism on basic English reading skills. We hypothesized that due to the proximity between the Russian and English orthographies as opposed to the Hebrew-English "distance," the Russian-Hebrew-speaking biliterate group who acquired basic reading and spelling skills in L1 Russian would have superior self-teaching in English as opposed to the two other groups. The standard two-session self-teaching paradigm was employed with naming (speed and accuracy) and orthographic choice as posttest measures of orthographic learning. Results showed that after 4 years of English instruction, all three groups showed evidence of self-teaching on naming speed and orthographic recognition. The Russian-Hebrew-speaking biliterate group, moreover, showed a partial advantage over the comparison groups for initial decoding of target pseudowords and clear-cut superiority for measures of later orthographic learning, thereby showing self-teaching while supporting the script dependence hypothesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Hemorrhage and blood loss-induced anemia associated with an acquired coagulation factor VIII inhibitor in a Thoroughbred mare.

PubMed

Winfield, Laramie S; Brooks, Marjory B

2014-03-15

A 23-year-old Thoroughbred mare was evaluated because of a coagulopathy causing hemoperitoneum, hematomas, and signs of blood loss-induced anemia. The mare had tachycardia, pallor, hypoperfusion, and a large mass in the right flank. The mass was further characterized ultrasonographically as an extensive hematoma in the body wall with associated hemoabdomen. Coagulation testing revealed persistent, specific prolongation of the activated partial thromboplastin time (> 100 seconds; reference interval, 24 to 44 seconds) attributable to severe factor VIII deficiency (12%; reference interval, 50% to 200%). On the basis of the horse's age, lack of previous signs of a bleeding diathesis, and subsequent quantification of plasma factor VIII inhibitory activity (Bethesda assay titer, 2.7 Bethesda units/mL), acquired hemophilia A was diagnosed. The medical history did not reveal risk factors or underlying diseases; thus, the development of inhibitory antibodies against factor VIII was considered to be idiopathic. The mare was treated with 2 transfusions of fresh whole blood and fresh-frozen plasma. Immunosuppressive treatment consisting of dexamethasone and azathioprine was initiated. Factor VIII deficiency and signs of coagulopathy resolved, and the inhibitory antibody titer decreased. The mare remained healthy with no relapse for at least 1 year after treatment. Horses may develop inhibitory antibodies against factor VIII that cause acquired hemophilia A. A treatment strategy combining transfusions of whole blood and fresh-frozen plasma and administration of immunosuppressive agents was effective and induced sustained remission for at least 1 year in the mare described here.

Histological characterization of regression in acquired immunodeficiency syndrome-related Kaposi's sarcoma.

PubMed

Pantanowitz, Liron; Dezube, Bruce J; Pinkus, Geraldine S; Tahan, Steven R

2004-01-01

Kaposi's sarcoma (KS) is an angioproliferative lesion that may regress or progress. Progression is related to spindle cell proliferation and the expression of human herpes virus-8 latency genes, including latent nuclear antigen-1 (LNA-1), cyclin-D1, and bcl-2. KS regression has not been well characterized histologically. Therefore, this study was undertaken to characterize the histopathology of pharmacologically induced regressed cutaneous KS. Skin punch biopsies from eight patients with acquired immunodeficiency syndrome (AIDS)-related KS, that regressed following chemotherapy with paclitaxel or the angiogenesis inhibitor Col-3, were investigated by light microscopy. Comparative immunophenotyping on pre- and post-treatment specimens for CD31, LNA-1, cyclin-D1, bcl-2, and CD117 (c-kit) was performed. Clinical and histologic features of regression were similar for paclitaxel and Col-3 treatment. On clinical examination, lesions flattened, became smaller, and lost their purple-red appearance, resulting in an orange-brown macule. Histological regression was divided into partial (n = 3) and complete (n = 5) regression. Partially regressed lesions had a significant reduction of spindle cells in the dermal interstitium, with residual spindle cells arranged around superficial and mid-dermal capillaries. Complete regression was characterized by an absence of detectable spindle cells, with a slight increase in capillaries of the superficial plexus. All regressed samples exhibited a prominent, superficial, perivascular, lymphocytic infiltrate and abundant dermal hemosiderin-laden macrophages. This clinicopathologic picture resembled the findings of pigmented purpura. CD31 staining correlated with the reduction of spindle cells. Regression was accompanied by a quantitative and qualitative decrease in LNA-1 and cyclin-D1 immunoreactivity, but no change in bcl-2 or c-kit expression. Pharmacologically induced regression of AIDS-related cutaneous KS is characterized by a complete loss or decrease of spindle cells, increased lymphocytes, and prominent dermal siderophage deposition. Without any prior knowledge of the history of KS regression following therapy, regressed KS lesions may be misdiagnosed clinically and histologically as pigmented purpuric dermatitis.

Application of Genetic Algorithm (GA) Assisted Partial Least Square (PLS) Analysis on Trilinear and Non-trilinear Fluorescence Data Sets to Quantify the Fluorophores in Multifluorophoric Mixtures: Improving Quantification Accuracy of Fluorimetric Estimations of Dilute Aqueous Mixtures.

PubMed

Kumar, Keshav

2018-03-01

Excitation-emission matrix fluorescence (EEMF) and total synchronous fluorescence spectroscopy (TSFS) are the 2 fluorescence techniques that are commonly used for the analysis of multifluorophoric mixtures. These 2 fluorescence techniques are conceptually different and provide certain advantages over each other. The manual analysis of such highly correlated large volume of EEMF and TSFS towards developing a calibration model is difficult. Partial least square (PLS) analysis can analyze the large volume of EEMF and TSFS data sets by finding important factors that maximize the correlation between the spectral and concentration information for each fluorophore. However, often the application of PLS analysis on entire data sets does not provide a robust calibration model and requires application of suitable pre-processing step. The present work evaluates the application of genetic algorithm (GA) analysis prior to PLS analysis on EEMF and TSFS data sets towards improving the precision and accuracy of the calibration model. The GA algorithm essentially combines the advantages provided by stochastic methods with those provided by deterministic approaches and can find the set of EEMF and TSFS variables that perfectly correlate well with the concentration of each of the fluorophores present in the multifluorophoric mixtures. The utility of the GA assisted PLS analysis is successfully validated using (i) EEMF data sets acquired for dilute aqueous mixture of four biomolecules and (ii) TSFS data sets acquired for dilute aqueous mixtures of four carcinogenic polycyclic aromatic hydrocarbons (PAHs) mixtures. In the present work, it is shown that by using the GA it is possible to significantly improve the accuracy and precision of the PLS calibration model developed for both EEMF and TSFS data set. Hence, GA must be considered as a useful pre-processing technique while developing an EEMF and TSFS calibration model.

Interception of the development of self tolerance in fetal lambs.

PubMed

McCullagh, P

1989-08-01

Investigation of the nature of immunological self tolerance has usually relied upon experimental protocols in which the tolerant state is interrupted in mature animals with the production of autoimmune disease. While such research has improved the understanding of those processes operative in overt autoimmunity, it has not been informative in relation to events associated with the establishment of self tolerance. Any description of this state which is to be based on observation will necessitate the use of experimental systems that permit observation of animals during the development of self tolerance. The present experiment entailed intervention approximately one third of the way through the gestation period of fetal lambs. An earlier experiment had established that 54-day fetal lambs would accept allografts of adult skin. This indicated that the capacity to discriminate between self and non-self had not been acquired at that age. Fetuses at this stage of gestation were submitted to either partial or total removal of the thyroid gland. The excised tissue was then implanted in nude mice for periods of 5 to 9 weeks. It was subsequently replaced subcutaneously, either in the original donor or in another fetus at a comparable stage of gestation. At postmortem examination, several weeks later, self implants in lambs from which the thyroid gland had been completely removed displayed autoimmune thyroiditis of varying degrees of severity. However, self implants in partially thyroidectomized animals were uniformly free from autoimmune manifestations. This implied that these reactions had not been directed against contaminating murine tissues in the implants replaced in completely thyroidectomized lambs. All allogeneic implants were subject to vey heavy lymphocytic infiltration, usually with accompanying necrosis consistent with allograft rejection. This was taken as an indication that hypothyroid fetal lambs had become immunocompetent by the time of thyroid reimplantation. Spontaneous immunological reactivity against reimplanted self thyroid tissue by thyroidectomized lambs was interpreted as a failure to acquire the capacity for self recognition as a result of antigen deprivation.

Archeointensity study on baked clay samples taken from the reconstructed ancient kiln: implication for validity of the Tsunakawa-Shaw paleointensity method

NASA Astrophysics Data System (ADS)

Yamamoto, Yuhji; Torii, Masayuki; Natsuhara, Nobuyoshi

2015-05-01

In 1972, a reconstruction experiment of a kiln had been done to reproduce an excavated kiln of the seventh century in Japan. Baked clay samples were taken from the floor surface and -20 cm level, and they have been stored after determinations of the paleomagnetic directions by partial alternating field demagnetizations. We recently applied the Tsunakawa-Shaw method to the samples to assess how reliable archeointensity results are obtained from the samples. A suite of the rock magnetic experiments and the scanning electron microscope observations elucidate that dominant magnetic carriers of the floor surface samples are Ti-poor titanomagnetite grains in approximately 10 nm size with single-domain and/or super-paramagnetic states, whereas contributions of multi-domain grains seem to be relatively large for the -20-cm level samples. From the floor surface samples, six out of the eight successful results were obtained and they give an average of 47.3 μT with a standard deviation of 2.2 μT. This is fairly consistent with the in situ geomagnetic field of 46.4 μT at the time of the reconstruction. They are obtained with a built-in anisotropy correction using anhysteretic remanent magnetization and without any cooling rate corrections. In contrast, only one out of four was successful from the -20-cm level samples. It yields an archeointensity of 31.6 μT, which is inconsistent with the in situ geomagnetic field. Considering from the in situ temperature record during the firing of the kiln and the unblocking temperature spectra of the samples, the floor surface samples acquired full thermoremanent magnetizations (TRMs) as their natural remanent magnetizations whereas the -20-cm level samples only acquired partial TRMs, and these differences probably cause the difference in the archeointensity results between the two sample groups. For archeointensity researches, baked clay samples from a kiln floor are considered to be ideal materials.

Repeated Structural Imaging Reveals Nonlinear Progression of Experience-Dependent Volume Changes in Human Motor Cortex.

PubMed

Wenger, Elisabeth; Kühn, Simone; Verrel, Julius; Mårtensson, Johan; Bodammer, Nils Christian; Lindenberger, Ulman; Lövdén, Martin

2017-05-01

Evidence for experience-dependent structural brain change in adult humans is accumulating. However, its time course is not well understood, as intervention studies typically consist of only 2 imaging sessions (before vs. after training). We acquired up to 18 structural magnetic resonance images over a 7-week period while 15 right-handed participants practiced left-hand writing and drawing. After 4 weeks, we observed increases in gray matter of both left and right primary motor cortices relative to a control group; 3 weeks later, these differences were no longer reliable. Time-series analyses revealed that gray matter in the primary motor cortices expanded during the first 4 weeks and then partially renormalized, in particular in the right hemisphere, despite continued practice and increasing task proficiency. Similar patterns of expansion followed by partial renormalization are also found in synaptogenesis, cortical map plasticity, and maturation, and may qualify as a general principle of structural plasticity. Research on human brain plasticity needs to encompass more than 2 measurement occasions to capture expansion and potential renormalization processes over time. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

PubMed Central

Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

2015-01-01

The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

Social foraging with partial (public) information.

PubMed

Mann, Ofri; Kiflawi, Moshe

2014-10-21

Group foragers can utilize public information to better estimate patch quality and arrive at more efficient patch-departure rules. However, acquiring such information may come at a cost; e.g. reduced search efficiency. We present a Bayesian group-foraging model in which social foragers do not require full awareness of their companions' foraging success; only of their number. In our model, patch departure is based on direct estimates of the number of remaining items. This is achieved by considering all likely combinations of initial patch-quality and group foraging-success; given the individual forager's experience within the patch. Slower rates of information-acquisition by our 'partially-aware' foragers lead them to over-utilize poor patches; more than fully-aware foragers. However, our model suggests that the ensuing loss in long-term intake-rates can be matched by a relatively low cost to the acquisition of full public information. In other words, we suggest that group-size offers sufficient information for optimal patch utilization by social foragers. We suggest, also, that our model is applicable to other situations where resources undergo 'background depletion', which is coincident but independent of the consumer's own utilization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Surgical management of third nerve palsy

PubMed Central

Singh, Anupam; Bahuguna, Chirag; Nagpal, Ritu; Kumar, Barun

2016-01-01

Third nerve paralysis has been known to be associated with a wide spectrum of presentation and other associated factors such as the presence of ptosis, pupillary involvement, amblyopia, aberrant regeneration, poor bell's phenomenon, superior oblique (SO) overaction, and lateral rectus (LR) contracture. Correction of strabismus due to third nerve palsy can be complex as four out of the six extraocular muscles are involved and therefore should be approached differently. Third nerve palsy can be congenital or acquired. The common causes of isolated third nerve palsy in children are congenital (43%), trauma (20%), inflammation (13%), aneurysm (7%), and ophthalmoplegic migraine. Whereas, in adult population, common etiologies are vasculopathic disorders (diabetes mellitus, hypertension), aneurysm, and trauma. Treatment can be both nonsurgical and surgical. As nonsurgical modalities are not of much help, surgery remains the main-stay of treatment. Surgical strategies are different for complete and partial third nerve palsy. Surgery for complete third nerve palsy may involve supra-maximal recession - resection of the recti. This may be combined with SO transposition and augmented by surgery on the other eye. For partial third nerve, palsy surgery is determined according to nature and extent of involvement of extraocular muscles. PMID:27433033

Origin of magnetization in lunar breccias - An example of thermal overprinting

NASA Technical Reports Server (NTRS)

Gose, W. A.; Strangway, D. W.; Pearce, G. W.

1978-01-01

Twenty six samples from seven hand specimens, collected from the station 6 boulder at the Apollo 17 landing site, were studied magnetically. The boulder is a breccia consisting of three lithologic units distinguished by their clast population. The direction of magnetization of samples from unit B which is almost devoid of large clasts cluster fairly well after alternating field demagnetization. Samples from unit C which is characterized by abundant large clasts up to 1 m in size do not contain a uniform direction of magnetization but the distribution is not random. Based on these data we propose that the natural remanent magnetization (NRM) in these breccias is the vector sum of two magnetizations, a pre-impact magnetization and a partial thermoremanence acquired during breccia formation. The relative contribution of the two components is controlled by the thermal history of the ejecta, which in turn is determined by its clast population. Depending on the clast population, the NRM can be a total thermoremanence, a partial thermoremanence plus a pre-impact magnetization, or a pre-impact magnetization. This model of thermal overprinting might be applicable to all lunar breccias of medium and higher metamorphic grade.

Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study**

PubMed Central

Palacios, Rosario; Santos, Jesús; Camino, Xavier; Arazo, Piedad; Torres Perea, Rafael; Echevarrfa, Santiago; Ribera, Esteban; Sánchez de la Rosa, Rainel; Moreno Guillen, Santiago

2005-01-01

Background: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. Objective: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. Methods: Patients eligible for participation in the Recover Study are aged10 ≥18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ≥3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ≥6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. Results: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18–67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6–156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]). Conclusions: The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART. PMID:24672118

[Effectiveness of partial and complete instrumental masking in chronic tinnitus. Studies with reference to retraining therapy].

PubMed

von Wedel, H; von Wedel, U C; Streppel, M; Walger, M

1997-09-01

Jastreboff und Hazell [9] developed a neurophysiological approach to tinnitus perception, including the important role of the central nervous system in the maintenance and intrusiveness of tinnitus. They introduced tinnitus-retraining therapy, consisting of four different strategies: (1) directive and person-centered counseling; (2) hearing aids and/or noise generators and/or environmental sounds; (3) psychological therapy; (4) adjacent therapies. Tinnitus should not be masked as with a tinnitus-masker, but must be able to be heard in addition to the noise! A noise generator or hearing aid should be worn at least 6-8 h per day over a period of up to 18 months. In additions several clinical visits are required in order to reinforce the counseling. The actual results show complete tinnitus remission for about 20-30% and partial remission for 50-60% of the patients [6]. We report on a retrospective study in patients wearing hearing aids or tinnitus-maskers over a period of 3 years. We compared the results of patients using partial tinnitus masking to those using complete masking. The tinnitus-related and general psychological complaints were acquired by the 52-item tinnitus questionnaire developed by Hallam et al. [4] and modified by Goebel and Hiller [3]. To describe the dimensions of tinnitus-related distress the scales are labelled emotional distress, cognitive distress, emotional and cognitive distress, intrusiveness, auditory perceptual difficulties, sleep disturbance and somatic complaints. Positive changes for the global tinnitus questionnaire score of more than 10 points are significant in the dimensions of tinnitus-related distress and are described as partial tinnitus-reduction. The group with partial masking effects can be compared to those performing retraining therapy to day because directive and personal centered counseling were integrated for all patients. Patients reporting partial masking effects through their aids (hearing aid or noise generator) showed more effective treatment results (reduced or disappeared tinnitus) than those using complete masking effects (P < 0.05). The reported results are improved by current investigations in Germany showing about 20-30% tinnitus remission and 50-60% significant reduction after 1 year of treatment [1]. Further scientific investigations must be carried out to evaluate the appropriateness and effectiveness of the retraining therapy and with regard to unique quality standards.

SU-E-J-214: Comparative Assessment On IGRT On Partial Bladder Cancer Treatment Between CT-On-Rails (CTOR) and KV Cone Beam CT (CBCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, T; Ma, C

2014-06-01

Purpose: Image-Guided radiation therapy(IGRT) depends on reliable online patient-specific anatomy information to address random and progressive anatomy changes. Large margins have been suggested to bladder cancer treatment due to large daily bladder anatomy variation. KV Cone beam CT(CBCT) has been used in IGRT localization prevalently; however, its lack of soft tissue contrast makes clinicians hesitate to perform daily soft tissue alignment with CBCT for partial bladder cancer treatment. This study compares the localization uncertainties of bladder cancer IGRT using CTon- Rails(CTOR) and CBCT. Methods: Three T2N0M0 bladder cancer patients (total of 66 Gy to partial bladder alone) were localized dailymore » with either CTOR or CBCT for their entire treatment course. A total of 71 sets of CTOR and 22 sets of CBCT images were acquired and registered with original planning CT scans by radiation therapists and approved by radiation oncologists for the daily treatment. CTOR scanning entailed 2mm slice thickness, 0.98mm axial voxel size, 120kVp and 240mAs. CBCT used a half fan pelvis protocol from Varian OBI system with 2mm slice thickness, 0.98axial voxel size, 125kVp, and 680mAs. Daily localization distribution was compared. Accuracy of CTOR and CBCT on partial bladder alignment was also evaluated by comparing bladder PTV coverage. Results: 1cm all around PTV margins were used in every patient except target superior limit margin to 0mm due to bowel constraint. Daily shifts on CTOR averaged to 0.48, 0.24, 0.19 mms(SI,Lat,AP directions); CBCT averaged to 0.43, 0.09, 0.19 mms(SI,Lat,AP directions). The CTOR daily localization showed superior results of V100% of PTV(102% CTOR vs. 89% CBCT) and bowel(Dmax 69.5Gy vs. 78Gy CBCT). CTOR images showed much higher contrast on bladder PTV alignment. Conclusion: CTOR daily localization for IGRT is more dosimetrically beneficial for partial bladder cancer treatment than kV CBCT localization and provided better soft tissue PTV identification.« less

Analytic image reconstruction from partial data for a single-scan cone-beam CT with scatter correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Min, Jonghwan; Pua, Rizza; Cho, Seungryong, E-mail: scho@kaist.ac.kr

Purpose: A beam-blocker composed of multiple strips is a useful gadget for scatter correction and/or for dose reduction in cone-beam CT (CBCT). However, the use of such a beam-blocker would yield cone-beam data that can be challenging for accurate image reconstruction from a single scan in the filtered-backprojection framework. The focus of the work was to develop an analytic image reconstruction method for CBCT that can be directly applied to partially blocked cone-beam data in conjunction with the scatter correction. Methods: The authors developed a rebinned backprojection-filteration (BPF) algorithm for reconstructing images from the partially blocked cone-beam data in amore » circular scan. The authors also proposed a beam-blocking geometry considering data redundancy such that an efficient scatter estimate can be acquired and sufficient data for BPF image reconstruction can be secured at the same time from a single scan without using any blocker motion. Additionally, scatter correction method and noise reduction scheme have been developed. The authors have performed both simulation and experimental studies to validate the rebinned BPF algorithm for image reconstruction from partially blocked cone-beam data. Quantitative evaluations of the reconstructed image quality were performed in the experimental studies. Results: The simulation study revealed that the developed reconstruction algorithm successfully reconstructs the images from the partial cone-beam data. In the experimental study, the proposed method effectively corrected for the scatter in each projection and reconstructed scatter-corrected images from a single scan. Reduction of cupping artifacts and an enhancement of the image contrast have been demonstrated. The image contrast has increased by a factor of about 2, and the image accuracy in terms of root-mean-square-error with respect to the fan-beam CT image has increased by more than 30%. Conclusions: The authors have successfully demonstrated that the proposed scanning method and image reconstruction algorithm can effectively estimate the scatter in cone-beam projections and produce tomographic images of nearly scatter-free quality. The authors believe that the proposed method would provide a fast and efficient CBCT scanning option to various applications particularly including head-and-neck scan.« less

The role of gray and white matter segmentation in quantitative proton MR spectroscopic imaging.

PubMed

Tal, Assaf; Kirov, Ivan I; Grossman, Robert I; Gonen, Oded

2012-12-01

Since the brain's gray matter (GM) and white matter (WM) metabolite concentrations differ, their partial volumes can vary the voxel's ¹H MR spectroscopy (¹H-MRS) signal, reducing sensitivity to changes. While single-voxel ¹H-MRS cannot differentiate between WM and GM signals, partial volume correction is feasible by MR spectroscopic imaging (MRSI) using segmentation of the MRI acquired for VOI placement. To determine the magnitude of this effect on metabolic quantification, we segmented a 1-mm³ resolution MRI into GM, WM and CSF masks that were co-registered with the MRSI grid to yield their partial volumes in approximately every 1 cm³ spectroscopic voxel. Each voxel then provided one equation with two unknowns: its i- metabolite's GM and WM concentrations C(i) (GM) , C(i) (WM) . With the voxels' GM and WM volumes as independent coefficients, the over-determined system of equations was solved for the global averaged C(i) (GM) and C(i) (WM) . Trading off local concentration differences offers three advantages: (i) higher sensitivity due to combined data from many voxels; (ii) improved specificity to WM versus GM changes; and (iii) reduced susceptibility to partial volume effects. These improvements made no additional demands on the protocol, measurement time or hardware. Applying this approach to 18 volunteered 3D MRSI sets of 480 voxels each yielded N-acetylaspartate, creatine, choline and myo-inositol C(i) (GM) concentrations of 8.5 ± 0.7, 6.9 ± 0.6, 1.2 ± 0.2, 5.3 ± 0.6 mM, respectively, and C(i) (WM) concentrations of 7.7 ± 0.6, 4.9 ± 0.5, 1.4 ± 0.1 and 4.4 ± 0.6mM, respectively. We showed that unaccounted voxel WM or GM partial volume can vary absolute quantification by 5-10% (more for ratios), which can often double the sample size required to establish statistical significance. Copyright © 2012 John Wiley & Sons, Ltd.

Transient Optical Sky survey

NASA Astrophysics Data System (ADS)

Hadjiyska, Elena Ivanova

2009-06-01

Optical transients have been studied in isolated cases, but never mapped into a comprehensive data base in the past. These events vary in duration and signature, yet they are united under the umbrella of time varying observables and represent a significant portion of the dynamical processes in the universe. The Transient Optical Sky Survey (TOSS) System is a dedicated, ground-based system of small optical telescopes, observing nightly at fixed Declination while gathering 90 sec exposures and thus creating a repeated partial map of the sky. Presented here is a brief overview of some of the signatures of transient events and a description of the TOSS system along with the data acquired during the 2008-2009 observing campaign, potentially producing over 100,000 light curves.

COMPUTATION OF ℛ IN AGE-STRUCTURED EPIDEMIOLOGICAL MODELS WITH MATERNAL AND TEMPORARY IMMUNITY.

PubMed

Feng, Zhilan; Han, Qing; Qiu, Zhipeng; Hill, Andrew N; Glasser, John W

2016-03-01

For infectious diseases such as pertussis, susceptibility is determined by immunity, which is chronological age-dependent. We consider an age-structured epidemiological model that accounts for both passively acquired maternal antibodies that decay and active immunity that wanes, permitting reinfection. The model is a 6-dimensional system of partial differential equations (PDE). By assuming constant rates within each age-group, the PDE system can be reduced to an ordinary differential equation (ODE) system with aging from one age-group to the next. We derive formulae for the effective reproduction number ℛ and provide their biological interpretation in some special cases. We show that the disease-free equilibrium is stable when ℛ < 1 and unstable if ℛ > 1.

Space Radar Image of Kliuchevskoi Volcano,Russia

NASA Technical Reports Server (NTRS)

1994-01-01

This photograph of the eruption of Kliuchevskoi volcano, Kamchatka, Russia was taken by space shuttle Endeavour astronauts during the early hours of the eruption on September 30, 1994. The ash plume, which reached heights of more than 18 kilometers (50,000 feet), is emerging from a vent on the north flank of Kliuchevskoi, partially hidden by the plume and its shadow in this view. The photograph is oriented with north toward the bottom, for comparison with the Spaceborne Imaging Radar C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) image (P-44823) that was acquired a few days later. Near the center of the photo, a small whitish steam plume may be seen emanating from the growing lava dome of a companion volcano, Bezymianny.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsvelik, A. M.; Yevtushenko, O. M.

We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z2 symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axismore » anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localizatioin.« less

Analysis of brain patterns using temporal measures

DOEpatents

Georgopoulos, Apostolos

2015-08-11

A set of brain data representing a time series of neurophysiologic activity acquired by spatially distributed sensors arranged to detect neural signaling of a brain (such as by the use of magnetoencephalography) is obtained. The set of brain data is processed to obtain a dynamic brain model based on a set of statistically-independent temporal measures, such as partial cross correlations, among groupings of different time series within the set of brain data. The dynamic brain model represents interactions between neural populations of the brain occurring close in time, such as with zero lag, for example. The dynamic brain model can be analyzed to obtain the neurophysiologic assessment of the brain. Data processing techniques may be used to assess structural or neurochemical brain pathologies.

Observer-based adaptive backstepping control for fractional order systems with input saturation.

PubMed

Sheng, Dian; Wei, Yiheng; Cheng, Songsong; Wang, Yong

2017-07-03

An observer-based fractional order anti-saturation adaptive backstepping control scheme is proposed for incommensurate fractional order systems with input saturation and partial measurable state in this paper. On the basis of stability analysis, a novel state observer is established first since the only information we could acquire is the system output. In order to compensate the saturation, a series of virtual signals are generated via the construction of fractional order auxiliary system. Afterwards, the controller design is carried out in accordance with the adaptive backstepping control method by introduction of the indirect Lyapunov method. To highlight the effectiveness of the proposed control scheme, simulation examples are demonstrated at last. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Directional tendencies of Hebrew, Japanese, and English readers.

PubMed

Nachson, I; Hatta, T

2001-08-01

Consistent left-right and right-left reading habits are associated with corresponding directional tendencies in the reproduction of horizontally displayed visual stimuli. Inconsistent reading habits should therefore be associated with inconsis tent directional tendencies. This hypothesis was tested on Japanese readers whose reading habits were inconsistent by asking them to reproduce four series of 12-item horizontal stimulus arrays. The hypothesis was partially supported by the data which showed that, like Hebrew readers who also have inconsistent reading habits, the directional tendencies shown by the 68 Japanese readers were significantly weaker on some tasks that those shown by the 16 English readers whose left-right reading habits were consistent. The data were interpreted as showing that acquired reading habits may affect directionality in perception of visual stimuli.

Simulation of partially coherent light propagation using parallel computing devices

NASA Astrophysics Data System (ADS)

Magalhães, Tiago C.; Rebordão, José M.

2017-08-01

Light acquires or loses coherence and coherence is one of the few optical observables. Spectra can be derived from coherence functions and understanding any interferometric experiment is also relying upon coherence functions. Beyond the two limiting cases (full coherence or incoherence) the coherence of light is always partial and it changes with propagation. We have implemented a code to compute the propagation of partially coherent light from the source plane to the observation plane using parallel computing devices (PCDs). In this paper, we restrict the propagation in free space only. To this end, we used the Open Computing Language (OpenCL) and the open-source toolkit PyOpenCL, which gives access to OpenCL parallel computation through Python. To test our code, we chose two coherence source models: an incoherent source and a Gaussian Schell-model source. In the former case, we divided into two different source shapes: circular and rectangular. The results were compared to the theoretical values. Our implemented code allows one to choose between the PyOpenCL implementation and a standard one, i.e using the CPU only. To test the computation time for each implementation (PyOpenCL and standard), we used several computer systems with different CPUs and GPUs. We used powers of two for the dimensions of the cross-spectral density matrix (e.g. 324, 644) and a significant speed increase is observed in the PyOpenCL implementation when compared to the standard one. This can be an important tool for studying new source models.

Geodetic exploration of strain along the El Pilar Fault in northeastern Venezuela

NASA Astrophysics Data System (ADS)

Reinoza, C.; Jouanne, F.; Audemard, F. A.; Schmitz, M.; Beck, C.

2015-03-01

We use Global Navigation Satellite Systems observations in northeastern Venezuela to constrain the El Pilar Fault (EPF) kinematics and to explore the effects of the variable elastic properties of the surrounding medium and of the fault geometry on inferred slip rates and locking depth. The velocity field exhibits an asymmetric velocity gradient on either side of the EPF. We use five different approaches to explore possible models to explain this asymmetry. First, we infer a 1.6 km locking depth using a classic elastic half-space dislocation model. Second, we infer a 1.5 km locking depth and a 0.33 asymmetry coefficient using a heterogeneous asymmetric model, including contrasting material properties on either side of a vertical fault, suggesting that the igneous-metamorphic terranes on the northern side are ~2 times more rigid than the sedimentary southern side. Third, we use a three-dimensional elastostatic model to evaluate the presence of a compliant zone, suggesting a 30% reduction of rigidity in the upper 3 km at the depth of a 1 to 5 km wide fault zone. Fourth, we evaluate the distribution of fault slip, revealing a widespread partial creep pattern in the eastern upper segment, while the upper western segment exhibits a partially locked area, which coincides with the rupture surface of the 1797 and 1929 earthquakes. To supplement these models, we upgrade the previously published displacement simulation method using nonvertical dislocations with data acquired between 2003 and 2013. The localized aseismic displacement pattern associated with creeping or partially creeping fault segments could explain the low level of historic seismicity.

Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karunamuni, Roshan; Bartsch, Hauke; White, Nathan S.

Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thicknessmore » between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.« less

Volumetric gain of the human pancreas after left partial pancreatic resection: A CT-scan based retrospective study.

PubMed

Phillip, Veit; Zahel, Tina; Danninger, Assiye; Erkan, Mert; Dobritz, Martin; Steiner, Jörg M; Kleeff, Jörg; Schmid, Roland M; Algül, Hana

2015-01-01

Regeneration of the pancreas has been well characterized in animal models. However, there are conflicting data on the regenerative capacity of the human pancreas. The aim of the present study was to assess the regenerative capacity of the human pancreas. In a retrospective study, data from patients undergoing left partial pancreatic resection at a single center were eligible for inclusion (n = 185). Volumetry was performed based on 5 mm CT-scans acquired through a 256-slice CT-scanner using a semi-automated software. Data from 24 patients (15 males/9 females) were included. Mean ± SD age was 68 ± 11 years (range, 40-85 years). Median time between surgery and the 1st postoperative CT was 9 days (range, 0-27 days; IQR, 7-13), 55 days (range, 21-141 days; IQR, 34-105) until the 2nd CT, and 191 days (range, 62-1902; IQR, 156-347) until the 3rd CT. The pancreatic volumes differed significantly between the first and the second postoperative CT scans (median volume 25.6 mL and 30.6 mL, respectively; p = 0.008) and had significantly increased further by the 3rd CT scan (median volume 37.9 mL; p = 0.001 for comparison with 1st CT scan and p = 0.003 for comparison with 2nd CT scan). The human pancreas shows a measurable and considerable potential of volumetric gain after partial resection. Multidetector-CT based semi-automated volume analysis is a feasible method for follow-up of the volume of the remaining pancreatic parenchyma after partial pancreatectomy. Effects on exocrine and endocrine pancreatic function have to be evaluated in a prospective manner. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Ergoregions in magnetized black hole spacetimes

NASA Astrophysics Data System (ADS)

Gibbons, G. W.; Mujtaba, A. H.; Pope, C. N.

2013-06-01

The spacetimes obtained by Ernst’s procedure for appending an external magnetic field B to a seed Kerr-Newman black hole are commonly believed to be asymptotic to the static Melvin metric. We show that this is not in general true. Unless the electric charge of the black hole satisfies Q= jB(1+{\\textstyle {\\frac{\\scriptstyle 1}{\\scriptstyle 4} } } j^2 B^4), where j is the angular momentum of the original seed solution, an ergoregion extends all the way from the black hole horizon to infinity. We find that if the condition on the electric charge is satisfied then the metric is asymptotic to the static Melvin metric, and the electromagnetic field carries not only magnetic, but also electric, flux along the axis. We give a self-contained account of the solution-generating procedure, including explicit formulae for the metric and the vector potential. In the case when Q= jB(1+{\\textstyle {\\frac{\\scriptstyle 1}{\\scriptstyle 4} } } j^2 B^4), we show that there is an arbitrariness in the choice of asymptotically timelike Killing field K_\\Omega = {\\partial }/{\\partial }t+ \\Omega \\, {\\partial }/{\\partial }\\phi, because there is no canonical choice of Ω. For one choice, Ω = Ωs, the metric is asymptotically static, and there is an ergoregion confined to the neighbourhood of the horizon. On the other hand, by choosing Ω = ΩH, so that K_{\\Omega _H} is co-rotating with the horizon, then for sufficiently large B numerical studies indicate there is no ergoregion at all. For smaller values, in a range B- < B < B+, there is a toroidal ergoregion outside and disjoint from the horizon. If B ⩽ B- this ergoregion expands all the way to infinity in a cylindrical region near to the rotation axis. For black holes whose size is small compared to the Melvin radius 2/B, and neglecting back-reaction of the electromagnetic field, we recover Wald’s result that it is energetically favourable for the hole to acquire a charge 2jB.

Estimating cardiorespiratory fitness in well-functioning older adults: treadmill validation of the long distance corridor walk.

PubMed

Simonsick, Eleanor M; Fan, Ellen; Fleg, Jerome L

2006-01-01

To determine criterion validity of the 400-m walk component of the Long Distance Corridor Walk (LDCW) and develop equations for estimating peak oxygen consumption (VO2) from 400-m time and factors intrinsic to test performance (e.g., heart rate (HR) and systolic blood pressure (SBP) response) in older adults. Cross-sectional validation study. Gerontology Research Center, National Institute on Aging, Baltimore, Maryland. Healthy volunteers (56 men and 46 women) aged 60 to 91 participating in the Baltimore Longitudinal Study of Aging between August 1999 and July 2000. The LDCW, consisting of a 2-minute walk followed immediately by a 400-m walk "done as quickly as possible" over a 20-m course was administered the day after maximal treadmill testing. HR and SBP were measured before testing and at the end of the 400-m walk. Weight, height, activity level, perceived effort, and stride length were also acquired. Peak VO2 ranged from 12.2 to 31.1 mL oxygen/kg per minute, and 400-m time ranged from 2 minutes 52 seconds to 6 minutes 18 seconds. Correlation between 400-m time and peak VO2 was -0.79. The estimating equation from linear regression included 400-m time (partial coefficient of determination (R2)=0.625), long versus short stride (partial R2=0.090), ending SBP (partial R2=0.019), and a correction factor for fast 400-m time (<240 seconds; partial R2=0.020) and explained 75.5% of the variance in peak VO2 (correlation coefficient=0.87). A 400-m walk performed as part of the LDCW provides a valid estimate of peak VO2 in older adults. Incorporating low-cost, safe assessments of fitness in clinical and research settings can identify early evidence of physical decline and individuals who may benefit from therapeutic interventions.

A study of 3π production in γp → n -π +π +π - and γ-p → Δ + +π +π -π - with CLAS at Jefferson Lab ->n

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsaris, Aristedis

2016-02-22

Apart from the mesons that the constituent quark model predicts, QCD allows for additional states beyond the qq system. Previous experiments have performed partial wave analysis on pion-production data and claim observation of an exotic J PC = 1 -+ state decaying via p-π. The g12 experiment took place at Jefferson Lab using the CLAS spectrometer, a liquid hydrogen target was used and a tagged photon beam. By studying the reactions γp → n -π +π +π - and γp → Δ + +π +π -π -, the photoproduction of mesons decaying to 3-pi was studied using two different butmore » complimentary channels. Events are selected with low four-momentum transfer to the baryon, in order to enhance one pion exchange production. For both 3-pi systems the data exhibit two intermediate decays, p-pi and f 2π. For the γp → n -π +π +π - reaction over 600k events were acquired resulting in the largest 3 photoproduction dataset to date. The exotic J PC = 1 -+ partial wave does not show resonant behavior and more so it is strongly consistent with a non-resonant non-interfering wave relative to a resonant π 2(1670). Furthermore, the partial wave analysis shows production of the a 2(1320) and π 2(1670) mesons. For the first time we report observation of a photoproduced a 1(1260) meson. For the γp → Δ + +π +π -π - reaction nearly 350k events were analyzed. A partial wave analysis was performed for the first time on this channel. The a1(1260), a2(1320), and the 2(1670) mesons were observed. Observation of the a1(1260) confirms the result first reported in γp → n -π +π +π - reaction.« less

Space Shuttle Transportation (Roll-Out) Loads Diagnostics

NASA Technical Reports Server (NTRS)

Elliott, Kenny B.; Buehrle, Ralph D.; James, George H.; Richart, Jene A.

2005-01-01

The Space Transportation System (STS) consists of three primary components; an Orbiter Vehicle, an External Fuel Tank, and two Solid Rocket Boosters. The Orbiter Vehicle and Solid Rocket Boosters are reusable components, and as such, they are susceptible to durability issues. Recently, the fatigue load spectra for these components have been updated to include load histories acquired during the rollout phase of the STS processing for flight. Using traditional program life assessment techniques, the incorporation of these "rollout" loads produced unacceptable life estimates for certain Orbiter structural members. As a result, the Space Shuttle System Engineering and Integration Office has initiated a program to re-assess the method used for developing the "rollout" loads and performing the life assessments. In the fall of 2003 a set of tests were preformed to provide information to either validate existing load spectra estimation techniques or generate new load spectra estimation methods. Acceleration and strain data were collected from two rollouts of a partial-stack configuration of the Space Shuttle. The partial stack configuration consists of two Solid Rocket Boosters tied together at the upper External Tank attachment locations mounted on the Mobile Launch Platform carried by a Crawler Transporter (CT). In the current analysis, the data collected from this test is examined for consistency in speed, surface condition effects, and the characterization of the forcing function. It is observed that the speed of the CT is relatively stable. The dynamic response acceleration of the partial-stack is slightly sensitive to the surface condition of the road used for transport, and the dynamic response acceleration of the partial-stack generally increases as the transport speed increases. However, the speed sensitivity is dependent on the measurement location. Finally, the character of the forcing function is narrow-banded with the primary drivers being harmonics of two CT speed dependent excitations. One source is an excitation due to the CT treads striking the road surface, and the second is unknown.

Histological correlation of 7 T multi-parametric MRI performed in ex-vivo Achilles tendon.

PubMed

Juras, Vladimir; Apprich, Sebastian; Pressl, Christina; Zbyn, Stefan; Szomolanyi, Pavol; Domayer, Stephan; Hofstaetter, Jochen G; Trattnig, Siegfried

2013-05-01

The goal of this in vitro validation study was to investigate the feasibility of biochemical MRI techniques, such as sodium imaging, T₂ mapping, fast imaging with steady state precession (FISP), and reversed FISP (PSIF), as potential markers for collagen, glycosaminoglycan and water content in the Achilles tendon. Five fresh cadaver ankles acquired from a local anatomy department were used in the study. To acquire a sodium signal from the Achilles tendon, a 3D-gradient-echo sequence, optimized for sodium imaging, was used with TE=7.71 ms and TR=17 ms. The T₂ relaxation times were obtained using a multi-echo, spin-echo technique with a repetition time (TR) of 1200 ms and six echo times. A 3D, partially balanced, steady-state gradient echo pulse sequence was used to acquire FISP and PSIF images, with TR/TE=6.96/2.46 ms. MRI parameters were correlated with each other, as well as with histologically assessed glycosaminoglycan and water content in cadaver Achilles tendons. The highest relevant Pearson correlation coefficient was found between sodium SNR and glycosaminoglycan content (r=0.71, p=0.007). Relatively high correlation was found between the PSIF signal and T2 values (r=0.51, p=0.036), and between the FISP signal and T₂ values (r=0.56, p=0.047). Other correlations were found to be below the moderate level. This study demonstrated the feasibility of progressive biochemical MRI methods for the imaging of the AT. A GAG-specific, contrast-free method (sodium imaging), as well as collagen- and water-sensitive methods (T₂ mapping, FISP, PSIF), may be used in fast-relaxing tissues, such as tendons, in reasonable scan times. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Overcoming food allergy through acquired tolerance conferred by transfer of Tregs in a murine model.

PubMed

Yamashita, H; Takahashi, K; Tanaka, H; Nagai, H; Inagaki, N

2012-02-01

The number of food allergy patients is increasing. Some children outgrow their food allergies through tolerance, whereas others remain susceptible throughout their lives. We aimed to contribute to food allergy therapeutics by understanding induction of oral tolerance in a murine food allergy model. We modified an existing murine food allergy model by using ovalbumin (OVA) to induce oral tolerance, either by pretreating mice with OVA or by transferring mesenteric lymph node (MLN) cells or T cells derived from mice treated with OVA. Pretreatment with OVA prevented food allergy, with complete suppression of OVA-specific immunoglobulin (Ig)E and IgA antibody production and interleukin (IL)-4, IL-10, and IL-9 mRNA expression. The proportion of regulatory T cells (Tregs) in MLN cells and expression of transforming growth factor-β mRNA increased. In the transfer model, anaphylaxis secondary to OVA intake was suppressed by transfer of whole MLN cells and Tregs from OVA-treated mice. However, OVA-specific IgE and IgA expressions were partially attenuated by transfer of antigen-specific and nonspecific Tregs, but not by whole MLN cells from OVA-treated mice. In the Treg transfer model, IL-4 and IL-10 mRNA expression decreased, but IL-9 mRNA expression increased. We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy. © 2011 John Wiley & Sons A/S.

Late L2ers can acquire grammatical features that do not occur in their L1: Evidence from the effect of animacy on verb agreement in L1 Chinese.

PubMed

Lempert, Henrietta

2016-05-01

Second language (L2) learners often have persistent difficulty with agreement between the number of the subject and the number of the verb. This study tested whether deviant L2 verb number agreement reflects maturational constraints on acquiring new grammatical features or resource limitations that impede access to the representations of L2 grammatical features. L1-Chinese undergraduate students at three age of arrival (AoA) levels were tested for online verb agreement accuracy by completing preambles in three animacy combinations: animate-inanimate [AI; e.g., The officer(s) from the station(s)], inanimate-animate [IA; e.g., The letters from the lawyer(s)], and inanimate-inanimate [II; e.g., The poster(s) from the museum(s)]. AI should be less costly to process than IA or II sequences, because animacy supports the subject in AI but competes with the subject for control of agreement in IA sequences, and is neutralized in II. Agreement accuracy was greater overall for AI than for IA or II, and although an AoA-related increase in erroneous agreement after plural subjects occurred for IA and II, there were no AoA effects for AI. Higher scores on memory tasks were associated with greater agreement accuracy, and the memory tasks significantly predicted variance in erroneous agreement when AoA was partialed out. The fact that even late learners can do verb agreement in the case of AI demonstrates that they can acquire new grammatical features. The greater difficulty with agreement in the case of IA or II than of AI, in conjunction with the results for the memory tasks, supports the resource limitation hypothesis.

t-Darpp overexpression in HER2-positive breast cancer confers a survival advantage in lapatinib.

PubMed

Christenson, Jessica L; Denny, Erin C; Kane, Susan E

2015-10-20

Drug resistance is a major barrier to successful cancer treatment. For patients with HER2-positive breast cancer who initially respond to therapy, the majority develop resistance within one year of treatment. Patient outcomes could improve significantly if we can find and exploit common mechanisms of acquired resistance to different targeted therapies. Overexpression of t-Darpp, a truncated form of the dual kinase/phosphatase inhibitor Darpp-32, has been linked to acquired resistance to trastuzumab, a front-line therapy for HER2-positive breast cancer. Darpp-32 reverses t-Darpp's effect on trastuzumab resistance. In this study, we examined whether t-Darpp could be involved in resistance to lapatinib, another HER2-targeted therapeutic. Lapatinib-resistant SKBR3 cells (SK/LapR) showed a marked change in the Darpp-32:t-Darpp ratio toward a predominance of t-Darpp. Overexpression of t-Darpp alone was not sufficient to confer lapatinib resistance, but cells that overexpress t-Darpp partially mimicked the molecular resistance phenotype observed in SK/LapR cells exposed to lapatinib. SK/LapR cells failed to down-regulate Survivin and failed to induce BIM accumulation in response to lapatinib; cells overexpressing t-Darpp exhibited only the failed BIM accumulation. t-Darpp knock-down reversed this phenotype. Using a fluorescence-based co-culture system, we found that cells overexpressing t-Darpp formed colonies in lapatinib within 3-4 weeks, whereas parental cells in the same co-culture did not. Overall, t-Darpp appears to mediate a survival advantage in lapatinib, possibly linked to failed lapatinib-induced BIM accumulation. t-Darpp might also be relevant to acquired resistance to other cancer drugs that rely on BIM accumulation to induce apoptosis.

Loss of Activating EGFR Mutant Gene Contributes to Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer Cells

PubMed Central

Kubo, Takuya; Murakami, Yuichi; Kawahara, Akihiko; Azuma, Koichi; Abe, Hideyuki; Kage, Masayoshi; Yoshinaga, Aki; Tahira, Tomoko; Hayashi, Kenshi; Arao, Tokuzo; Nishio, Kazuto; Rosell, Rafael; Kuwano, Michihiko; Ono, Mayumi

2012-01-01

Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11–18, which harbored activating EGFR mutations. One erlotinib-resistant cell line from PC9 and two erlotinib-resistant cell lines and two gefitinib-resistant cell lines from 11–18 were independently established. Almost complete loss of mutant delE746-A750 EGFR gene was observed in the erlotinib-resistant cells isolated from PC9, and partial loss of the mutant L858R EGFR gene copy was specifically observed in the erlotinib- and gefitinib-resistant cells from 11–18. However, constitutive activation of EGFR downstream signaling, PI3K/Akt, was observed even after loss of the mutated EGFR gene in all resistant cell lines even in the presence of the drug. In the erlotinib-resistant cells from PC9, constitutive PI3K/Akt activation was effectively inhibited by lapatinib (a dual TKI of EGFR and HER2) or BIBW2992 (pan-TKI of EGFR family proteins). Furthermore, erlotinib with either HER2 or HER3 knockdown by their cognate siRNAs also inhibited PI3K/Akt activation. Transfection of activating mutant EGFR complementary DNA restored drug sensitivity in the erlotinib-resistant cell line. Our study indicates that loss of addiction to mutant EGFR resulted in gain of addiction to both HER2/HER3 and PI3K/Akt signaling to acquire EGFR-TKI resistance. PMID:22815900

Quantitative metrics for evaluating parallel acquisition techniques in diffusion tensor imaging at 3 Tesla.

PubMed

Ardekani, Siamak; Selva, Luis; Sayre, James; Sinha, Usha

2006-11-01

Single-shot echo-planar based diffusion tensor imaging is prone to geometric and intensity distortions. Parallel imaging is a means of reducing these distortions while preserving spatial resolution. A quantitative comparison at 3 T of parallel imaging for diffusion tensor images (DTI) using k-space (generalized auto-calibrating partially parallel acquisitions; GRAPPA) and image domain (sensitivity encoding; SENSE) reconstructions at different acceleration factors, R, is reported here. Images were evaluated using 8 human subjects with repeated scans for 2 subjects to estimate reproducibility. Mutual information (MI) was used to assess the global changes in geometric distortions. The effects of parallel imaging techniques on random noise and reconstruction artifacts were evaluated by placing 26 regions of interest and computing the standard deviation of apparent diffusion coefficient and fractional anisotropy along with the error of fitting the data to the diffusion model (residual error). The larger positive values in mutual information index with increasing R values confirmed the anticipated decrease in distortions. Further, the MI index of GRAPPA sequences for a given R factor was larger than the corresponding mSENSE images. The residual error was lowest in the images acquired without parallel imaging and among the parallel reconstruction methods, the R = 2 acquisitions had the least error. The standard deviation, accuracy, and reproducibility of the apparent diffusion coefficient and fractional anisotropy in homogenous tissue regions showed that GRAPPA acquired with R = 2 had the least amount of systematic and random noise and of these, significant differences with mSENSE, R = 2 were found only for the fractional anisotropy index. Evaluation of the current implementation of parallel reconstruction algorithms identified GRAPPA acquired with R = 2 as optimal for diffusion tensor imaging.

Acquiring neural signals for developing a perception and cognition model

NASA Astrophysics Data System (ADS)

Li, Wei; Li, Yunyi; Chen, Genshe; Shen, Dan; Blasch, Erik; Pham, Khanh; Lynch, Robert

2012-06-01

The understanding of how humans process information, determine salience, and combine seemingly unrelated information is essential to automated processing of large amounts of information that is partially relevant, or of unknown relevance. Recent neurological science research in human perception, and in information science regarding contextbased modeling, provides us with a theoretical basis for using a bottom-up approach for automating the management of large amounts of information in ways directly useful for human operators. However, integration of human intelligence into a game theoretic framework for dynamic and adaptive decision support needs a perception and cognition model. For the purpose of cognitive modeling, we present a brain-computer-interface (BCI) based humanoid robot system to acquire brainwaves during human mental activities of imagining a humanoid robot-walking behavior. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model. The BCI system consists of a data acquisition unit with an electroencephalograph (EEG), a humanoid robot, and a charge couple CCD camera. An EEG electrode cup acquires brainwaves from the skin surface on scalp. The humanoid robot has 20 degrees of freedom (DOFs); 12 DOFs located on hips, knees, and ankles for humanoid robot walking, 6 DOFs on shoulders and arms for arms motion, and 2 DOFs for head yaw and pitch motion. The CCD camera takes video clips of the human subject's hand postures to identify mental activities that are correlated to the robot-walking behaviors. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model.

Schistosomiasis mansoni in Bananal (State of São Paulo, Brazil): IV. Study on the public awareness of its risks in the Palha District.

PubMed

da Silva, Rubens Antonio; de Carvalho, Maria Esther; Zacharias, Fabiana; de Lima, Valquíria R; Teles, Horacio M S

2002-01-01

A rather high prevalence of mansoni schistosomiasis has been observed in some localities of Bananal, State of São Paulo, during the past decade. The highest prevalence of schistosomiasis was found in the Palha District; it was thus considered adequate for an evaluation of public awareness of the risks involved in acquiring schistosomiasis, a likely outcome of certain behavior patterns. We interviewed 542 district-dwellers. The 5-to-39 age-group constituted 65.5% of the whole sample. Concerning the infection, 69.2% had hearsay information; 46.1% know the infection; 69.6% know how it is acquired; 31.5% know about the symptoms and 57.1% know what can be done to avoid infection; 17.7% declared to have acquired the infection at least once in their lifetime; 62.3% reported total or partial immersion in collections of water of Bananal, once or twice a week, 53.9% of these for bathing or fishing. Although most (91.7%) households have treated running water, are connected to the sewage network or have septic tanks, 9% of the people interviewed use to defecate on the field. It became clear that the educational messages aimed at this population had not been adequate, having failed to fulfil any expectations. The local people received only piecemeal and subjective information about their problem. The control of schistosomiasis requires an integrated practice, which includes the analysis of macro-determinant factors, such as basic sanitation, habitation, education and health care. In short, we require a multidisciplinary vision of the mechanisms of transmission of the infection, which depends upon adequate planning and well trained personnel, intent on their educational work, to attain satisfactory results.

Non-destructive assessment of grapevine water status in the field using a portable NIR spectrophotometer.

PubMed

Tardaguila, Javier; Fernández-Novales, Juan; Gutiérrez, Salvador; Diago, Maria Paz

2017-08-01

Until now, the majority of methods employed to assess grapevine water status have been destructive, time-intensive, costly and provide information of a limited number of samples, thus the ability of revealing within-field water status variability is reduced. The goal of this work was to evaluate the capability of non-invasive, portable near infrared (NIR) spectroscopy acquired in the field, to assess the grapevine water status in diverse varieties, grown under different environmental conditions, in a fast and reliable way. The research was conducted 2 weeks before harvest in 2012, in two commercial vineyards, planted with eight different varieties. Spectral measurements were acquired in the field on the adaxial and abaxial sides of 160 individual leaves (20 leaves per variety) using a commercially available handheld spectrophotometer (1600-2400 nm). Principal component analysis (PCA) and modified partial least squares (MPLS) were used to interpret the spectra and to develop reliable prediction models for stem water potential (Ψ s ) (cross-validation correlation coefficient (r cv ) ranged from 0.77 to 0.93, and standard error of cross validation (SECV) ranged from 0.10 to 0.23), and leaf relative water content (RWC) (r cv ranged from 0.66 to 0.81, and SECV between 1.93 and 3.20). The performance differences between models built from abaxial and adaxial-acquired spectra is also discussed. The capability of non-invasive NIR spectroscopy to reliably assess the grapevine water status under field conditions was proved. This technique can be a suitable and promising tool to appraise within-field variability of plant water status, helpful to define optimised irrigation strategies in the wine industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Good syndrome and other causes of cytomegalovirus retinitis in HIV-negative patients-case report and comprehensive review of the literature.

PubMed

Downes, Kenneth M; Tarasewicz, Dariusz; Weisberg, Laurie J; Cunningham, Emmett T

2016-12-01

We describe a 65-year-old Thai woman who developed cytomegalovirus retinitis (CMVR) in the setting of Good syndrome-a rare, acquired partial immune deficiency caused by thymoma. The patient subsequently developed vitritis with cystoid macular edema (CME) similar to immune recovery uveitis (IRU) despite control of the retinitis with antiviral agents. A comprehensive review of the literature through December, 2014, identified an additional 279 eyes of 208 patients with CMVR in the absence of human immunodeficiency virus (HIV) infection. Including our newly reported case, 9 of the 208 patients (4.3 %) had Good syndrome. Twenty-one of the 208 patients (10.1 %) had CMVR related to intraocular or periocular corticosteroid administration. The remaining 178 patients (85.6 %) acquired CMVR from other causes. Within the subset of patients who did not have Good syndrome or did not acquire CMVR followed by intraocular or periocular corticosteroid administration, there were many other factors contributing to a decline in immune function. The most common included age over 60 years (33.1 %), an underlying malignancy (28.7 %), a systemic autoimmune disorder requiring systemic immunosuppression (19.1 %), organ (15.2 %) or bone marrow (16.3 %) transplantation requiring systemic immunosuppression, and diabetes mellitus (6.1 %). Only 4.5 % of the patients had no identifiable contributor to a decline in immune function. While the clinical features of CMVR are generally similar in HIV-negative and HIV-positive patients, the rates of moderate to severe intraocular inflammation and of occlusive retinal vasculitis appear to be higher in HIV-negative patients.

Implicit and explicit second language training recruit common neural mechanisms for syntactic processing.

PubMed

Batterink, Laura; Neville, Helen

2013-06-01

In contrast to native language acquisition, adult second-language (L2) acquisition occurs under highly variable learning conditions. Although most adults acquire their L2 at least partially through explicit instruction, as in a classroom setting, many others acquire their L2 primarily through implicit exposure, as is typical of an immersion environment. Whether these differences in acquisition environment play a role in determining the neural mechanisms that are ultimately recruited to process L2 grammar has not been well characterized. This study investigated this issue by comparing the ERP response to novel L2 syntactic rules acquired under conditions of implicit exposure and explicit instruction, using a novel laboratory language-learning paradigm. Native speakers tested on these stimuli showed a biphasic response to syntactic violations, consisting of an earlier negativity followed by a later P600 effect. After merely an hour of training, both implicitly and explicitly trained learners who were capable of detecting grammatical violations also elicited P600 effects. In contrast, learners who were unable to discriminate between grammatically correct and incorrect sentences did not show significant P600 effects. The magnitude of the P600 effect was found to correlate with learners' behavioral proficiency. Behavioral measures revealed that successful learners from both the implicit and explicit groups gained explicit, verbalizable knowledge about the L2 grammar rules. Taken together, these results indicate that late, controlled mechanisms indexed by the P600 play a crucial role in processing a late-learned L2 grammar, regardless of training condition. These findings underscore the remarkable plasticity of later, attention-dependent processes and their importance in lifelong learning.

How children perceive fractals: Hierarchical self-similarity and cognitive development

PubMed Central

Martins, Maurício Dias; Laaha, Sabine; Freiberger, Eva Maria; Choi, Soonja; Fitch, W. Tecumseh

2014-01-01

The ability to understand and generate hierarchical structures is a crucial component of human cognition, available in language, music, mathematics and problem solving. Recursion is a particularly useful mechanism for generating complex hierarchies by means of self-embedding rules. In the visual domain, fractals are recursive structures in which simple transformation rules generate hierarchies of infinite depth. Research on how children acquire these rules can provide valuable insight into the cognitive requirements and learning constraints of recursion. Here, we used fractals to investigate the acquisition of recursion in the visual domain, and probed for correlations with grammar comprehension and general intelligence. We compared second (n = 26) and fourth graders (n = 26) in their ability to represent two types of rules for generating hierarchical structures: Recursive rules, on the one hand, which generate new hierarchical levels; and iterative rules, on the other hand, which merely insert items within hierarchies without generating new levels. We found that the majority of fourth graders, but not second graders, were able to represent both recursive and iterative rules. This difference was partially accounted by second graders’ impairment in detecting hierarchical mistakes, and correlated with between-grade differences in grammar comprehension tasks. Empirically, recursion and iteration also differed in at least one crucial aspect: While the ability to learn recursive rules seemed to depend on the previous acquisition of simple iterative representations, the opposite was not true, i.e., children were able to acquire iterative rules before they acquired recursive representations. These results suggest that the acquisition of recursion in vision follows learning constraints similar to the acquisition of recursion in language, and that both domains share cognitive resources involved in hierarchical processing. PMID:24955884

ESR1 mutations as a mechanism for acquired endocrine resistance in breast cancer

PubMed Central

Jeselsohn, Rinath; Buchwalter, Gilles; De Angelis, Carmine; Brown, Myles; Schiff, Rachel

2016-01-01

Most breast cancers are estrogen receptor α (ER)-positive (+) and are treated with endocrine therapies targeting ER activity. Despite efforts, the mechanisms of the frequent clinical resistance to these therapies remain largely unknown. Several recent parallel studies unveiled gain-of-function recurrent ESR1 mutations in up to 20% of patients with metastatic ER+ disease who all received endocrine therapies, which for more cases included an aromatase inhibitor. These mutations, clustered in a hotspot within the ligand-binding domain (LBD), lead to ligand independent ER activity and tumor growth, partial resistance to tamoxifen and fulvestrant, and potentially increased metastatic capacity. Together, these findings suggest that the ESR1 LBD mutations account for acquired endocrine resistance in a substantial fraction of patients with metastatic disease. The absence of detectable ESR1 mutations in treatment-naïve disease and the correlation with the number of endocrine treatments indicate a clonal expansion of rare mutant clones, selected under the pressure of treatment. New technologies to detect low/ultra rare ESR1 mutations together with tissue and liquid biopsies are required to fully expose their clinical relevance in prognosis and treatment. Pre-clinical and clinical development of rationale-based novel therapeutic strategies to inhibit these mutants has the potential to substantially improve treatment outcomes. PMID:26122181

Preliminary Comparisons of the Information Content and Utility of TM Versus MSS Data

NASA Technical Reports Server (NTRS)

Markham, B. L.

1984-01-01

Comparisons were made between subscenes from the first TM scene acquired of the Washington, D.C. area and a MSS scene acquired approximately one year earlier. Three types of analyses were conducted to compare TM and MSS data: a water body analysis, a principal components analysis and a spectral clustering analysis. The water body analysis compared the capability of the TM to the MSS for detecting small uniform targets. Of the 59 ponds located on aerial photographs 34 (58%) were detected by the TM with six commission errors (15%) and 13 (22%) were detected by the MSS with three commission errors (19%). The smallest water body detected by the TM was 16 meters; the smallest detected by the MSS was 40 meters. For the principal components analysis, means and covariance matrices were calculated for each subscene, and principal components images generated and characterized. In the spectral clustering comparison each scene was independently clustered and the clusters were assigned to informational classes. The preliminary comparison indicated that TM data provides enhancements over MSS in terms of (1) small target detection and (2) data dimensionality (even with 4-band data). The extra dimension, partially resultant from TM band 1, appears useful for built-up/non-built-up area separation.

The BIM deletion polymorphism: A paradigm of a permissive interaction between germline and acquired TKI resistance factors in chronic myeloid leukemia.

PubMed

Ko, Tun Kiat; Chin, Hui San; Chuah, Charles T H; Huang, John W J; Ng, King-Pan; Khaw, Seong Lin; Huang, David C S; Ong, S Tiong

2016-01-19

Both germline polymorphisms and tumor-specific genetic alterations can determine the response of a cancer to a given therapy. We previously reported a germline deletion polymorphism in the BIM gene that was sufficient to mediate intrinsic resistance to tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), as well as other cancers [1]. The deletion polymorphism favored the generation of BIM splice forms lacking the pro-apoptotic BH3 domain, conferring a relative resistance to the TKI imatinib (IM). However, CML patients with the BIM deletion polymorphism developed both partial and complete IM resistance. To understand the mechanisms underlying the latter, we grew CML cells either with or without the BIM deletion polymorphism in increasing IM concentrations. Under these conditions, the BIM deletion polymorphism enhanced the emergence of populations with complete IM resistance, mimicking the situation in patients. Importantly, the combined use of TKIs with the BH3 mimetic ABT-737 overcame the BCR-ABL1-dependent and -independent resistance mechanisms found in these cells. Our results illustrate the interplay between germline and acquired genetic factors in confering TKI resistance, and suggest a therapeutic strategy for patients with complete TKI resistance associated with the BIM deletion polymorphism.

Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

PubMed

Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathy D; Draber, Peter; Stepanek, Ondrej

2018-05-11

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8 + T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein.

PubMed

Deeg, Christoph M; Hassan, Ebrahim; Mutz, Pascal; Rheinemann, Lara; Götz, Veronika; Magar, Linda; Schilling, Mirjam; Kallfass, Carsten; Nürnberger, Cindy; Soubies, Sébastien; Kochs, Georg; Haller, Otto; Schwemmle, Martin; Staeheli, Peter

2017-05-01

Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population. © 2017 Deeg et al.

A low cost mobile phone dark-field microscope for nanoparticle-based quantitative studies.

PubMed

Sun, Dali; Hu, Tony Y

2018-01-15

Dark-field microscope (DFM) analysis of nanoparticle binding signal is highly useful for a variety of research and biomedical applications, but current applications for nanoparticle quantification rely on expensive DFM systems. The cost, size, limited robustness of these DFMs limits their utility for non-laboratory settings. Most nanoparticle analyses use high-magnification DFM images, which are labor intensive to acquire and subject to operator bias. Low-magnification DFM image capture is faster, but is subject to background from surface artifacts and debris, although image processing can partially compensate for background signal. We thus mated an LED light source, a dark-field condenser and a 20× objective lens with a mobile phone camera to create an inexpensive, portable and robust DFM system suitable for use in non-laboratory conditions. This proof-of-concept mobile DFM device weighs less than 400g and costs less than $2000, but analysis of images captured with this device reveal similar nanoparticle quantitation results to those acquired with a much larger and more expensive desktop DFMM system. Our results suggest that similar devices may be useful for quantification of stable, nanoparticle-based activity and quantitation assays in resource-limited areas where conventional assay approaches are not practical. Copyright © 2017 Elsevier B.V. All rights reserved.

An open, comparative study of 10% potassium hydroxide solution versus salicylic and lactic acid combination in the treatment of molluscum contagiosum in children.

PubMed

Köse, Osman; Özmen, İbrahim; Arca, Ercan

2013-08-01

To evaluate and compare the safety and efficacy of 10% potassium hydroxide (KOH) solution and salicylic and lactic acid (SAL + LAC) combination in the treatment of molluscum contagiosum (MC). 26 patients with MC randomized into two treatment groups. 12 patients treated with 10% KOH solution and 14 patients treated with SAL + LAC combination for 6 weeks. Parents of patients were instructed to apply medication once daily only to lesions at study onset. Assessment of response of the treated lesions and side effects was performed at 2, 4 and 6 weeks of the treatment. Newly acquired lesions were not included in the study. At the end of therapy, 83.3% (n = 10) of KOH group demonstrated complete remission and 16.7% (n = 2) of them showed partial remission; four patients (33%) developed new lesions during the study. All the patients in the SAL + LAC combination group (100%) demonstrated complete remission of study entry lesions at the end of 6 weeks with five patients (35%) acquiring new lesions during the study. Minor side effects were observed in two groups. 10% KOH solution and SAL + LAC combination were found to be equally effective in the treatment of MC in children.

[Recurrent nevus: Case-report about a pagetoid form occurring from a congenital nevus in infancy].

PubMed

Bompy, L; Levasseur, J; Hallier, A; Fraitag, S; Aubriot-Lorton, M-H; Bonniaud, B; Zwetyenga, N

2018-04-03

Recurrent nevus (RN) is a cutaneous benign tumour with similarities with malignant lesions. Typically, it occurs after a partial resection of commun-acquired nevus. Its incidence varies from 0.3 to 27% according to the studies. We present here a pediatric case of a pagetoid form of a recurrent nevus occurring from a congenital nevus. A congenital nevus was removed from a 9-month-old girl. Pathologists concluded to a commun-acquired nevus of complete exeresis. Two other cutaneous lesions appeared and we decided to realise a total removal. Analysis showed a recurrent nevus with some atypical histological features. No recurrence has occurred during the three post-operative of follow-up. It is an interesting case because of the occurrence of a RN after the removal of a congenital nevus in a child. Furthermore, it displayed some atypical histological features. Practicians, such as surgeons, dermatologists or pathologists, have to be aware of the risk of misdiagnosis with this lesion, which presents some similarities with SSM melanoma. It would be interesting to determinate some markers to statuate about its benign feature. There is no management recommendation about this lesion but it seems to be necessary to remove it to eliminate a malignant tumour. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cortisol modifies extinction learning of recently acquired fear in men

PubMed Central

Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

2014-01-01

Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS−) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS− than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS− differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear. PMID:23945999

In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein

PubMed Central

Magar, Linda; Schilling, Mirjam; Kallfass, Carsten; Nürnberger, Cindy; Soubies, Sébastien; Kochs, Georg; Schwemmle, Martin

2017-01-01

Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population. PMID:28396461

Changes in visceral adipose tissue plasma membrane lipid composition in old rats are associated with adipocyte hypertrophy with aging.

PubMed

Bonzón-Kulichenko, Elena; Moltó, Eduardo; Pintado, Cristina; Fernández, Alejandro; Arribas, Carmen; Schwudke, Dominik; Gallardo, Nilda; Shevchenko, Andrej; Andrés, Antonio

2018-04-16

Increased adiposity, through adipocyte hypertrophy and/or hyperplasia, characterizes aging and obesity. Both are leptin-resistant states, associated to disturbed lipid metabolism, reduced insulin sensitivity and inflammation. Nevertheless, fat tissue dysfunction appears earlier in obesity than in normal aging. In contrast, lipodystrophy is accompanied by diabetes, and improving the fat cell capacity to expand rescues the diabetic phenotype. Fat tissue dysfunction is extensively studied in the diet-induced obesity, but remains relatively neglected in the aging-associated obesity. In the Wistar rat, as occurs in humans, early or middle aging is accompanied by an increase in adiposity. Using this experimental model, we describe the molecular mechanisms contributing to the white adipose tissue (WAT) hypertrophy. WAT from middle-old age rats is characterized by decreased basal lipogenesis and lipolysis, increased esterification, as demonstrated by the higher TAG and cholesterol content in visceral WAT, and the maintenance of total ceramide levels within normal values. In addition, we describe alterations in the adipose tissue plasma membrane lipid composition, as increased total ether-phosphatidylcholine, sphingomyelin and free cholesterol levels that favor an enlarged fat cell size with aging. All these metabolic changes may be regarded as a survival advantage that prevents the aged rats from becoming overtly diabetic.

Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Shurong; Risques, Rosa Ana; Martin, George M.

2008-01-01

LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. Tomore » our surprise, these abnormalities were also observed in lines overexpressing wild-type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes.« less

Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice.

PubMed

Garcia, Jose M; Scherer, Thomas; Chen, Ji-an; Guillory, Bobby; Nassif, Anriada; Papusha, Victor; Smiechowska, Joanna; Asnicar, Mark; Buettner, Christoph; Smith, Roy G

2013-09-01

Cachexia, defined as an involuntary weight loss ≥ 5%, is a serious and dose-limiting side effect of chemotherapy that decreases survival in cancer patients. Alterations in lipid metabolism are thought to cause the lipodystrophy commonly associated with cachexia. Ghrelin has been proposed to ameliorate the alterations in lipid metabolism due to its orexigenic and anabolic properties. However, the mechanisms of action through which ghrelin could potentially ameliorate chemotherapy-associated cachexia have not been elucidated. The objectives of this study were to identify mechanisms by which the chemotherapeutic agent cisplatin alters lipid metabolism and to establish the role of ghrelin in reversing cachexia. Cisplatin-induced weight and fat loss were prevented by ghrelin. Cisplatin increased markers of lipolysis in white adipose tissue (WAT) and of β-oxidation in liver and WAT and suppressed lipogenesis in liver, WAT, and muscle. Ghrelin prevented the imbalance between lipolysis, β-oxidation, and lipogenesis in WAT and muscle. Pair-feeding experiments demonstrated that the effects of cisplatin and ghrelin on lipogenesis, but not on lipolysis and β-oxidation, were due to a reduction in food intake. Thus, ghrelin prevents cisplatin-induced weight and fat loss by restoring adipose tissue functionality. An increase in caloric intake further enhances the anabolic effects of ghrelin.

Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906.

PubMed

Tajima, Kazuki; Shirakawa, Jun; Togashi, Yu; Yamazaki, Shunsuke; Okuyama, Tomoko; Kyohara, Mayu; Konishi, Hiromi; Terauchi, Yasuo

2017-06-23

Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28). On day 7, the visceral white fat mass was significantly reduced in mice treated with OSI-906 accompanied by a reduced expression of leptin and an increased expression of the lipolysis-related genes Lpl and Atgl. Interestingly, the lipoatrophy and the observed changes in gene expression were completely reversed on day 14. Similarly, liver steatosis and β cell proliferation were transiently observed on day 7 but had disappeared by day 14. Taken together, these results suggest that this model for the acute inhibition of systemic IR/IGF1R signaling may be useful for investigating the recovery from metabolic disorders induced by impaired growth factor signaling.

Objective evidence for the use of polylactic acid implants in HIV-associated facial lipoatrophy using three-dimensional surface laser scanning and psychological assessment.

PubMed

Ong, J; Clarke, A; White, P; Johnson, M A; Withey, S; Butler, P E M

2009-12-01

The advent of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of people infected with human immunodeficiency virus (HIV). Although patients often have excellent disease control with these combinations of antiretrovirals, they are at risk for the multiple toxicities associated with these drugs. Facial lipoatrophy is a particularly distressing complication of some HAART regimes. This disfigurement can lead to significant psychosocial stress, resulting in decreased treatment compliance. Polylactic acid (PLA) facial implants provide a potential method of restoring a normal appearance. One hundred consecutive patients had a course of PLA facial implants. All patients were assessed clinically and had photographs, facial surface laser scans and completed psychological questionnaires throughout the course of treatment. After a mean of 4.85 treatments per patient, there were improvements in all measures. The mean clinical scores improved from a moderate-severe grade to none-mild grade after treatment. Three-dimensional (3D) laser surface scans showed a volume increase of 2.81 cc over the treated area of the cheek. There were significant improvements in all of the psychological measures. This study shows clear objective evidence of the psychological and physical benefit of PLA implants in HIV-associated facial lipodystrophy.

Copy number variation in metabolic phenotypes.

PubMed

Lanktree, M; Hegele, R A

2008-01-01

Despite successes in identifying genetic contributors to common metabolic phenotypes, only part of the heritable component of these traits has thus far been explained. Copy number variation (CNV) is likely to be responsible for some of the unexplained variation. As observed with single nucleotide changes, it is probable that both rare and common CNVs will contribute to susceptibility to metabolic disease. For instance, CNVs in the LDLR gene underlie a substantial portion of disease in patients with heterozygous familial hypercholesterolemia. As well, a common CNV in LPA encoding apolipoprotein(a) is the primary determinant of plasma lipoprotein(a) concentrations, a risk factor for atherosclerosis. Recent efforts to map CNVs in control populations have defined their size, frequency and distribution. Many of the identified CNVs overlap genes with important functions in metabolic pathways. The overlap of CNVs that were found in control datasets with functional candidate genes or genes with previous evidence of association with metabolic syndrome presents an important subset for future CNV association studies. Finally, we describe an approach to search for CNVs in a rare high-penetrance metabolic disorder, namely lipodystrophy. As methods to identify CNVs increase in precision and accuracy, the prospect of identifying their role in both rare Mendelian and common complex metabolic phenotypes will become a reality. Copyright 2009 S. Karger AG, Basel.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

PubMed

Josse, G; Gensanne, D; Aquilina, C; Bernard, J; Saint-Martory, C; Lagarde, J M; Schmitt, A M

2009-04-01

Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

Gender recognition from unconstrained and articulated human body.

PubMed

Wu, Qin; Guo, Guodong

2014-01-01

Gender recognition has many useful applications, ranging from business intelligence to image search and social activity analysis. Traditional research on gender recognition focuses on face images in a constrained environment. This paper proposes a method for gender recognition in articulated human body images acquired from an unconstrained environment in the real world. A systematic study of some critical issues in body-based gender recognition, such as which body parts are informative, how many body parts are needed to combine together, and what representations are good for articulated body-based gender recognition, is also presented. This paper also pursues data fusion schemes and efficient feature dimensionality reduction based on the partial least squares estimation. Extensive experiments are performed on two unconstrained databases which have not been explored before for gender recognition.

Immunosuppressive therapy for patients with Down syndrome and idiopathic aplastic anemia.

PubMed

Suzuki, Kyogo; Muramatsu, Hideki; Okuno, Yusuke; Narita, Atsushi; Hama, Asahito; Takahashi, Yoshiyuki; Yoshida, Makoto; Horikoshi, Yasuo; Watanabe, Ken-Ichiro; Kudo, Kazuko; Kojima, Seiji

2016-07-01

Idiopathic aplastic anemia (AA) is a rare hematological complication of Down syndrome (DS). The safety and efficacy of immunosuppressive therapy (IST) in individuals with DS remain unknown. We used a standard regimen of IST, comprising antithymocyte globulin and cyclosporine A, to treat three children with DS and idiopathic acquired AA. Two patients achieved a hematological (complete or partial) response and became transfusion independent at the final follow-up. The third patient failed to respond to IST and underwent bone marrow transplantation from a human leukocyte antigen (HLA)-mismatched unrelated donor. None of the patients experienced severe or unexpected adverse events during IST. Our experience suggests that IST is a safe and reasonable treatment, even in individuals with DS who suffer from AA and lack an HLA-matched sibling donor.

Gender Recognition from Unconstrained and Articulated Human Body

PubMed Central

Wu, Qin; Guo, Guodong

2014-01-01

Gender recognition has many useful applications, ranging from business intelligence to image search and social activity analysis. Traditional research on gender recognition focuses on face images in a constrained environment. This paper proposes a method for gender recognition in articulated human body images acquired from an unconstrained environment in the real world. A systematic study of some critical issues in body-based gender recognition, such as which body parts are informative, how many body parts are needed to combine together, and what representations are good for articulated body-based gender recognition, is also presented. This paper also pursues data fusion schemes and efficient feature dimensionality reduction based on the partial least squares estimation. Extensive experiments are performed on two unconstrained databases which have not been explored before for gender recognition. PMID:24977203

Quantum phase transition and protected ideal transport in a Kondo chain

DOE PAGES

Tsvelik, A. M.; Yevtushenko, O. M.

2015-11-30

We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z2 symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axismore » anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localizatioin.« less

Space Radar Image of Kliuchevskoi Volcano,Russia

NASA Image and Video Library

1999-05-01

This photograph of the eruption of Kliuchevskoi volcano, Kamchatka, Russia was taken by space shuttle Endeavour astronauts during the early hours of the eruption on September 30, 1994. The ash plume, which reached heights of more than 18 kilometers (50,000 feet), is emerging from a vent on the north flank of Kliuchevskoi, partially hidden by the plume and its shadow in this view. The photograph is oriented with north toward the bottom, for comparison with the Spaceborne Imaging Radar C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) image (P-44823) that was acquired a few days later. Near the center of the photo, a small whitish steam plume may be seen emanating from the growing lava dome of a companion volcano, Bezymianny. http://photojournal.jpl.nasa.gov/catalog/PIA01766

Conditioned Reinforcement and Response Strength

PubMed Central

Shahan, Timothy A

2010-01-01

Stimuli associated with primary reinforcers appear themselves to acquire the capacity to strengthen behavior. This paper reviews research on the strengthening effects of conditioned reinforcers within the context of contemporary quantitative choice theories and behavioral momentum theory. Based partially on the finding that variations in parameters of conditioned reinforcement appear not to affect response strength as measured by resistance to change, long-standing assertions that conditioned reinforcers do not strengthen behavior in a reinforcement-like fashion are considered. A signposts or means-to-an-end account is explored and appears to provide a plausible alternative interpretation of the effects of stimuli associated with primary reinforcers. Related suggestions that primary reinforcers also might not have their effects via a strengthening process are explored and found to be worthy of serious consideration. PMID:20885815

Polarization-Dependent Ti 2p-Resonant X-ray Raman Scattering from Ti2O3

NASA Astrophysics Data System (ADS)

Tezuka, Yasuhisa; Nakajima, Nobuo; Adachi, Jun-ichi; Morimoto, Osamu; Sato, Hitoshi; Uozumi, Takayuki

2017-12-01

Detailed resonant X-ray emission spectra (XES) and these polarization dependences of Ti2O3 were obtained by excitation at the Ti 2p absorption edge. About 100 XES spectra were observed in different polarization configurations. X-ray Raman scattering spectra showed two types of crystal field (dd) excitations as well as charge-transfer (CT) excitations. Bulk states of the powder sample were obtained by the XES measurement, which is the photon-in/photon-out method. Partial photon yields (PPYs) of some elementary excitations were extracted from the XES spectra. The CT excitations were hidden in total electron yield spectra, but these were revealed by PPY measurements. Symmetry information of these excitations was acquired on the basis of polarization dependences.

The Effect of Bioturbation on Relative Paleointenstiy Records

NASA Astrophysics Data System (ADS)

Egli, R.; Zhao, X.; Gilder, S. A.

2015-12-01

Bioturbation is one of the key factors affecting the acquisition of a natural remanent magnetization (NRM) in sediments featuring a top mixed layer. In this case, a rotational diffusion process controls the acquisition timing, which is described in terms of a lock-in function, and NRM intensity. In general terms, NRM acquisition by rotational diffusion is described by a Smoluchowski-Debye differential equation, which yields analytical solutions describing how an initially acquired depositional remanent magnetization (DRM) is progressively replaced by a post-depositional remanent magnetization (PDRM) [Egli and Mao, Geochem. Geophys. Geosyst. 16, 995-1016, 2015]. These solutions in turn support the calculation of lock-in functions. Results are controlled by the following parameters: (1) a rotation diffusivity constant γ = 2DrL/ω, where Dr is the rotational diffusion coefficient, L the thickness of the mixed layer, and ω the sedimentation rate, and (2) the ratio between magnetic aligning torques τm = mB and the torques τp associated with mechanical interactions between sediment particles and with the action of perturbing forces. The PDRM acquisition rate and the extent of DRM replacement is controlled by γ, while PDRM intensity is a Langevin function of τm/ τp. Associated lock-in functions range from a constant (NRM is acquired only at the sediment surface) to the classical lock-in function starting below the mixed layer, though intermediate situations where PDRM is partially acquired in the mixed layer. This model has been confirmed by redeposition experiments performed with fresh sediment containing living microorganisms. Redeposition experiments show that the intensity of bioturbation-driven PDRMs can reach ~50% of the originally acquired DRM. Our model has profound consequences for the evaluation of relative paleointensity records, where variations can be driven by changes of the depositional environment. While this knowledge is not new, we provide for the first time a key for understanding, in a quantitative manner, how the NRM acquisition efficiency is controlled by bioturbation. A combination of proxies leading to estimates of the bioturbation activity might provide a new path for improving the reliability of relative paleointensity records.

A glucose biosensor based on partially unzipped carbon nanotubes.

PubMed

Hu, Huifang; Feng, Miao; Zhan, Hongbing

2015-08-15

An amperometric glucose biosensor based on direct electron transfer of glucose oxidase (GOD) self-assembled on the surface of partially unzipped carbon nanotubes (PUCNTs) modified glassy carbon electrode (GCE) has been successfully fabricated. PUCNTs were synthesized via a facile chemical oxidative etching CNTs and used as a novel immobilization matrix for GOD. The cyclic voltammetric result of the PUCNT/GOD/GCE showed a pair of well-defined and quasi-reversible redox peaks with a formal potential of -0.470V and a peak to peak separation of 37mV, revealing that the fast direct electron transfer between GOD and the electrode has been achieved. It is notable that the glucose determination has been achieved in mediator-free condition. The developed biosensor displayed satisfactory analytical performance toward glucose including high sensitivity (19.50μA mM(-1)cm(-2)), low apparent Michaelis-Menten (5.09mM), a wide linear range of 0-17mM, and also preventing the interference from ascorbic acid, uric acid and dopamine usually coexisting with glucose in human blood. In addition, the biosensor acquired excellent storage stabilities. This facile, fast, environment-friendly and economical preparation strategy of PUCNT-GOD may provide a new platform for the fabrication of biocompatible glucose biosensors and other types of biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.; Fritz, T. E.; Tolle, D. V.; Jackson, W. E.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d -1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d -1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (> 1yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d -1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d -1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

Inspection of thick welded joints using laser-ultrasonic SAFT.

PubMed

Lévesque, D; Asaumi, Y; Lord, M; Bescond, C; Hatanaka, H; Tagami, M; Monchalin, J-P

2016-07-01

The detection of defects in thick butt joints in the early phase of multi-pass arc welding would be very valuable to reduce cost and time in the necessity of reworking. As a non-contact method, the laser-ultrasonic technique (LUT) has the potential for the automated inspection of welds, ultimately online during manufacturing. In this study, testing has been carried out using LUT combined with the synthetic aperture focusing technique (SAFT) on 25 and 50mm thick butt welded joints of steel both completed and partially welded. EDM slits of 2 or 3mm height were inserted at different depths in the multi-pass welding process to simulate a lack of fusion. Line scans transverse to the weld are performed with the generation and detection laser spots superimposed directly on the surface of the weld bead. A CCD line camera is used to simultaneously acquire the surface profile for correction in the SAFT processing. All artificial defects but also real defects are visualized in the investigated thick butt weld specimens, either completed or partially welded after a given number of passes. The results obtained clearly show the potential of using the LUT with SAFT for the automated inspection of arc welds or hybrid laser-arc welds during manufacturing. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Adaptive Signal Recovery on Graphs via Harmonic Analysis for Experimental Design in Neuroimaging.

PubMed

Kim, Won Hwa; Hwang, Seong Jae; Adluru, Nagesh; Johnson, Sterling C; Singh, Vikas

2016-10-01

Consider an experimental design of a neuroimaging study, where we need to obtain p measurements for each participant in a setting where p ' (< p ) are cheaper and easier to acquire while the remaining ( p - p ') are expensive. For example, the p ' measurements may include demographics, cognitive scores or routinely offered imaging scans while the ( p - p ') measurements may correspond to more expensive types of brain image scans with a higher participant burden. In this scenario, it seems reasonable to seek an "adaptive" design for data acquisition so as to minimize the cost of the study without compromising statistical power. We show how this problem can be solved via harmonic analysis of a band-limited graph whose vertices correspond to participants and our goal is to fully recover a multi-variate signal on the nodes, given the full set of cheaper features and a partial set of more expensive measurements. This is accomplished using an adaptive query strategy derived from probing the properties of the graph in the frequency space. To demonstrate the benefits that this framework can provide, we present experimental evaluations on two independent neuroimaging studies and show that our proposed method can reliably recover the true signal with only partial observations directly yielding substantial financial savings.

Mixture design and treatment methods for recycling contaminated sediment.

PubMed

Wang, Lei; Kwok, June S H; Tsang, Daniel C W; Poon, Chi-Sun

2015-01-01

Conventional marine disposal of contaminated sediment presents significant financial and environmental burden. This study aimed to recycle the contaminated sediment by assessing the roles and integration of binder formulation, sediment pretreatment, curing method, and waste inclusion in stabilization/solidification. The results demonstrated that the 28-d compressive strength of sediment blocks produced with coal fly ash and lime partially replacing cement at a binder-to-sediment ratio of 3:7 could be used as fill materials for construction. The X-ray diffraction analysis revealed that hydration products (calcium hydroxide) were difficult to form at high sediment content. Thermal pretreatment of sediment removed 90% of indigenous organic matter, significantly increased the compressive strength, and enabled reuse as non-load-bearing masonry units. Besides, 2-h CO2 curing accelerated early-stage carbonation inside the porous structure, sequestered 5.6% of CO2 (by weight) in the sediment blocks, and acquired strength comparable to 7-d curing. Thermogravimetric analysis indicated substantial weight loss corresponding to decomposition of poorly and well crystalline calcium carbonate. Moreover, partial replacement of contaminated sediment by various granular waste materials notably augmented the strength of sediment blocks. The metal leachability of sediment blocks was minimal and acceptable for reuse. These results suggest that contaminated sediment should be viewed as useful resources. Copyright © 2014 Elsevier B.V. All rights reserved.

Adaptation of the Haloarcula hispanica CRISPR-Cas system to a purified virus strictly requires a priming process

PubMed Central

Li, Ming; Wang, Rui; Zhao, Dahe; Xiang, Hua

2014-01-01

The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system mediates adaptive immunity against foreign nucleic acids in prokaryotes. However, efficient adaptation of a native CRISPR to purified viruses has only been observed for the type II-A system from a Streptococcus thermophilus industry strain, and rarely reported for laboratory strains. Here, we provide a second native system showing efficient adaptation. Infected by a newly isolated virus HHPV-2, Haloarcula hispanica type I-B CRISPR system acquired spacers discriminatively from viral sequences. Unexpectedly, in addition to Cas1, Cas2 and Cas4, this process also requires Cas3 and at least partial Cascade proteins, which are involved in interference and/or CRISPR RNA maturation. Intriguingly, a preexisting spacer partially matching a viral sequence is also required, and spacer acquisition from upstream and downstream sequences of its target sequence (i.e. priming protospacer) shows different strand bias. These evidences strongly indicate that adaptation in this system strictly requires a priming process. This requirement, if validated also true for other CRISPR systems as implied by our bioinformatic analysis, may help to explain failures to observe efficient adaptation to purified viruses in many laboratory strains, and the discrimination mechanism at the adaptation level that has confused scientists for years. PMID:24265226

Working Memory and Reinforcement Schedule Jointly Determine Reinforcement Learning in Children: Potential Implications for Behavioral Parent Training

PubMed Central

Segers, Elien; Beckers, Tom; Geurts, Hilde; Claes, Laurence; Danckaerts, Marina; van der Oord, Saskia

2018-01-01

Introduction: Behavioral Parent Training (BPT) is often provided for childhood psychiatric disorders. These disorders have been shown to be associated with working memory impairments. BPT is based on operant learning principles, yet how operant principles shape behavior (through the partial reinforcement (PRF) extinction effect, i.e., greater resistance to extinction that is created when behavior is reinforced partially rather than continuously) and the potential role of working memory therein is scarcely studied in children. This study explored the PRF extinction effect and the role of working memory therein using experimental tasks in typically developing children. Methods: Ninety-seven children (age 6–10) completed a working memory task and an operant learning task, in which children acquired a response-sequence rule under either continuous or PRF (120 trials), followed by an extinction phase (80 trials). Data of 88 children were used for analysis. Results: The PRF extinction effect was confirmed: We observed slower acquisition and extinction in the PRF condition as compared to the continuous reinforcement (CRF) condition. Working memory was negatively related to acquisition but not extinction performance. Conclusion: Both reinforcement contingencies and working memory relate to acquisition performance. Potential implications for BPT are that decreasing working memory load may enhance the chance of optimally learning through reinforcement. PMID:29643822

Hierarchical auto-configuration addressing in mobile ad hoc networks (HAAM)

NASA Astrophysics Data System (ADS)

Ram Srikumar, P.; Sumathy, S.

2017-11-01

Addressing plays a vital role in networking to identify devices uniquely. A device must be assigned with a unique address in order to participate in the data communication in any network. Different protocols defining different types of addressing are proposed in literature. Address auto-configuration is a key requirement for self organizing networks. Existing auto-configuration based addressing protocols require broadcasting probes to all the nodes in the network before assigning a proper address to a new node. This needs further broadcasts to reflect the status of the acquired address in the network. Such methods incur high communication overheads due to repetitive flooding. To address this overhead, a new partially stateful address allocation scheme, namely Hierarchical Auto-configuration Addressing (HAAM) scheme is extended and proposed. Hierarchical addressing basically reduces latency and overhead caused during address configuration. Partially stateful addressing algorithm assigns addresses without the need for flooding and global state awareness, which in turn reduces the communication overhead and space complexity respectively. Nodes are assigned addresses hierarchically to maintain the graph of the network as a spanning tree which helps in effectively avoiding the broadcast storm problem. Proposed algorithm for HAAM handles network splits and merges efficiently in large scale mobile ad hoc networks incurring low communication overheads.

Inter-costal Liver Ablation Under Real Time MR-Thermometry With Partial Activation Of A HIFU Phased Array Transducer

NASA Astrophysics Data System (ADS)

Quesson, Bruno; Merle, Mathilde; Köhler, Max; Mougenot, Charles; Roujol, Sebastien; de Senneville, Baudouin Denis; Moonen, Chrit

2010-03-01

HIFU ablation of tumours located inside the liver is hampered by the rib cage, which partially obstructs the beam path and may create adverse effects such as skin burns. This study presents a method for selectively deactivating the transducer elements causing undesired temperature increases near the bones. A manual segmentation of the bones visualized on 3D anatomical MR images acquired prior to sonication was performed to identify the beam obstruction. The resulting mask was projected (ray tracing starting from the focal point) on the transducer and elements with more than 50% obstruction of their active surface were deactivated. The effectiveness of the method for HIFU ablations is demonstrated ex vivo and in vivo in the liver of pigs with real-time MR thermometry, using the proton resonant frequency (PRF) method. For both ex vivo and in vivo experiments, the temperature increase near the bones was significantly reduced when the elements located in front of the ribs were deactivated. The temperature evolution at the focal point were similar, indicative of the absence of loss of heating efficacy when the elements were deactivated. This method is simple, rapid and reliable and allows to perform intercostal MRgHIFU ablation of the liver while sparing the ribs.

Event-related potential correlates of declarative and non-declarative sequence knowledge.

PubMed

Ferdinand, Nicola K; Rünger, Dennis; Frensch, Peter A; Mecklinger, Axel

2010-07-01

The goal of the present study was to demonstrate that declarative and non-declarative knowledge acquired in an incidental sequence learning task contributes differentially to memory retrieval and leads to dissociable ERP signatures in a recognition memory task. For this purpose, participants performed a sequence learning task and were classified as verbalizers, partial verbalizers, or nonverbalizers according to their ability to verbally report the systematic response sequence. Thereafter, ERPs were recorded in a recognition memory task time-locked to sequence triplets that were either part of the previously learned sequence or not. Although all three groups executed old sequence triplets faster than new triplets in the recognition memory task, qualitatively distinct ERP patterns were found for participants with and without reportable knowledge. Verbalizers and, to a lesser extent, partial verbalizers showed an ERP correlate of recollection for parts of the incidentally learned sequence. In contrast, nonverbalizers showed a different ERP effect with a reverse polarity that might reflect priming. This indicates that an ensemble of qualitatively different processes is at work when declarative and non-declarative sequence knowledge is retrieved. By this, our findings favor a multiple-systems view postulating that explicit and implicit learning are supported by different and functionally independent systems. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Rapid detection of talcum powder in tea using FT-IR spectroscopy coupled with chemometrics

PubMed Central

Li, Xiaoli; Zhang, Yuying; He, Yong

2016-01-01

This paper investigated the feasibility of Fourier transform infrared transmission (FT-IR) spectroscopy to detect talcum powder illegally added in tea based on chemometric methods. Firstly, 210 samples of tea powder with 13 dose levels of talcum powder were prepared for FT-IR spectra acquirement. In order to highlight the slight variations in FT-IR spectra, smoothing, normalize and standard normal variate (SNV) were employed to preprocess the raw spectra. Among them, SNV preprocessing had the best performance with high correlation of prediction (RP = 0.948) and low root mean square error of prediction (RMSEP = 0.108) of partial least squares (PLS) model. Then 18 characteristic wavenumbers were selected based on a hybrid of backward interval partial least squares (biPLS) regression, competitive adaptive reweighted sampling (CARS) algorithm and successive projections algorithm (SPA). These characteristic wavenumbers only accounted for 0.64% of the full wavenumbers. Following that, 18 characteristic wavenumbers were used to build linear and nonlinear determination models by PLS regression and extreme learning machine (ELM), respectively. The optimal model with RP = 0.963 and RMSEP = 0.137 was achieved by ELM algorithm. These results demonstrated that FT-IR spectroscopy with chemometrics could be used successfully to detect talcum powder in tea. PMID:27468701

Solid-phase cadmium speciation in soil using L3-edge XANES spectroscopy with partial least-squares regression.

PubMed

Siebers, Nina; Kruse, Jens; Eckhardt, Kai-Uwe; Hu, Yongfeng; Leinweber, Peter

2012-07-01

Cadmium (Cd) has a high toxicity and resolving its speciation in soil is challenging but essential for estimating the environmental risk. In this study partial least-square (PLS) regression was tested for its capability to deconvolute Cd L(3)-edge X-ray absorption near-edge structure (XANES) spectra of multi-compound mixtures. For this, a library of Cd reference compound spectra and a spectrum of a soil sample were acquired. A good coefficient of determination (R(2)) of Cd compounds in mixtures was obtained for the PLS model using binary and ternary mixtures of various Cd reference compounds proving the validity of this approach. In order to describe complex systems like soil, multi-compound mixtures of a variety of Cd compounds must be included in the PLS model. The obtained PLS regression model was then applied to a highly Cd-contaminated soil revealing Cd(3)(PO(4))(2) (36.1%), Cd(NO(3))(2)·4H(2)O (24.5%), Cd(OH)(2) (21.7%), CdCO(3) (17.1%) and CdCl(2) (0.4%). These preliminary results proved that PLS regression is a promising approach for a direct determination of Cd speciation in the solid phase of a soil sample.

A comparison of five standard methods for evaluating image intensity uniformity in partially parallel imaging MRI

PubMed Central

Goerner, Frank L.; Duong, Timothy; Stafford, R. Jason; Clarke, Geoffrey D.

2013-01-01

Purpose: To investigate the utility of five different standard measurement methods for determining image uniformity for partially parallel imaging (PPI) acquisitions in terms of consistency across a variety of pulse sequences and reconstruction strategies. Methods: Images were produced with a phantom using a 12-channel head matrix coil in a 3T MRI system (TIM TRIO, Siemens Medical Solutions, Erlangen, Germany). Images produced using echo-planar, fast spin echo, gradient echo, and balanced steady state free precession pulse sequences were evaluated. Two different PPI reconstruction methods were investigated, generalized autocalibrating partially parallel acquisition algorithm (GRAPPA) and modified sensitivity-encoding (mSENSE) with acceleration factors (R) of 2, 3, and 4. Additionally images were acquired with conventional, two-dimensional Fourier imaging methods (R = 1). Five measurement methods of uniformity, recommended by the American College of Radiology (ACR) and the National Electrical Manufacturers Association (NEMA) were considered. The methods investigated were (1) an ACR method and a (2) NEMA method for calculating the peak deviation nonuniformity, (3) a modification of a NEMA method used to produce a gray scale uniformity map, (4) determining the normalized absolute average deviation uniformity, and (5) a NEMA method that focused on 17 areas of the image to measure uniformity. Changes in uniformity as a function of reconstruction method at the same R-value were also investigated. Two-way analysis of variance (ANOVA) was used to determine whether R-value or reconstruction method had a greater influence on signal intensity uniformity measurements for partially parallel MRI. Results: Two of the methods studied had consistently negative slopes when signal intensity uniformity was plotted against R-value. The results obtained comparing mSENSE against GRAPPA found no consistent difference between GRAPPA and mSENSE with regard to signal intensity uniformity. The results of the two-way ANOVA analysis suggest that R-value and pulse sequence type produce the largest influences on uniformity and PPI reconstruction method had relatively little effect. Conclusions: Two of the methods of measuring signal intensity uniformity, described by the (NEMA) MRI standards, consistently indicated a decrease in uniformity with an increase in R-value. Other methods investigated did not demonstrate consistent results for evaluating signal uniformity in MR images obtained by partially parallel methods. However, because the spatial distribution of noise affects uniformity, it is recommended that additional uniformity quality metrics be investigated for partially parallel MR images. PMID:23927345

Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malinowski, Kathleen T.; Fischell Department of Bioengineering, University of Maryland, College Park, MD; McAvoy, Thomas J.

2012-04-01

Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precisionmore » in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.« less

WE-G-18A-08: Axial Cone Beam DBPF Reconstruction with Three-Dimensional Weighting and Butterfly Filtering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, S; Wang, W; Tang, X

2014-06-15

Purpose: With the major benefit in dealing with data truncation for ROI reconstruction, the algorithm of differentiated backprojection followed by Hilbert filtering (DBPF) is originally derived for image reconstruction from parallel- or fan-beam data. To extend its application for axial CB scan, we proposed the integration of the DBPF algorithm with 3-D weighting. In this work, we further propose the incorporation of Butterfly filtering into the 3-D weighted axial CB-DBPF algorithm and conduct an evaluation to verify its performance. Methods: Given an axial scan, tomographic images are reconstructed by the DBPF algorithm with 3-D weighting, in which streak artifacts existmore » along the direction of Hilbert filtering. Recognizing this orientation-specific behavior, a pair of orthogonal Butterfly filtering is applied on the reconstructed images with the horizontal and vertical Hilbert filtering correspondingly. In addition, the Butterfly filtering can also be utilized for streak artifact suppression in the scenarios wherein only partial scan data with an angular range as small as 270° are available. Results: Preliminary data show that, with the correspondingly applied Butterfly filtering, the streak artifacts existing in the images reconstructed by the 3-D weighted DBPF algorithm can be suppressed to an unnoticeable level. Moreover, the Butterfly filtering also works at the scenarios of partial scan, though the 3-D weighting scheme may have to be dropped because of no sufficient projection data are available. Conclusion: As an algorithmic step, the incorporation of Butterfly filtering enables the DBPF algorithm for CB image reconstruction from data acquired along either a full or partial axial scan.« less

Direct estimation of 17 O MR images (DIESIS) for quantification of oxygen metabolism in the human brain with partial volume correction.

PubMed

Kurzhunov, Dmitry; Borowiak, Robert; Reisert, Marco; Özen, Ali Caglar; Bock, Michael

2018-05-16

To provide a data post-processing method that corrects for partial volume effects (PVE) and fast T2* decay in dynamic 17 O MRI for the mapping of cerebral metabolic rates of oxygen consumption (CMRO 2 ). CMRO 2 is altered in neurodegenerative diseases and tumors and can be measured after 17 O gas inhalation using dynamic 17 O MRI. CMRO 2 quantification is difficult because of PVE. To correct for PVE, a direct estimation of the MR images (DIESIS) method is proposed and used in 4 dynamic 17 O MRI data sets of a healthy volunteer acquired on a 3T MRI system. With DIESIS, 17 O MR signal time curves in selected regions were directly estimated based on parcellation of a coregistered 1 H MPRAGE image. Profile likelihood analysis of the DIESIS method showed identifiability of CMRO 2 . In white matter (WM), DIESES reduced CMRO 2 from 0.97 ± 0.25 µmol/g tissue /min with Kaiser-Bessel gridding reconstruction to 0.85 ± 0.21 µmol/g tissue /min, whereas in gray matter (GM) it increases from 1.3 ± 0.31 µmol/g tissue /min to 1.86 ± 0.36 µmol/g tissue /min; both values are closer to the literature values from the 15 O-PET studies. DIESIS provided an increased separation of CMRO 2 values in GM and WM brain regions and corrected for partial volume effects in 17 O-MRI inhalation experiments. DIESIS could also be applied to more heterogeneous tissues such as glioblastomas if subregions of the tumor can be represented as additional parcels. © 2018 International Society for Magnetic Resonance in Medicine.

Using Remote Sensing Data to Evaluate Surface Soil Properties in Alabama Ultisols

NASA Technical Reports Server (NTRS)

Sullivan, Dana G.; Shaw, Joey N.; Rickman, Doug; Mask, Paul L.; Luvall, Jeff

2005-01-01

Evaluation of surface soil properties via remote sensing could facilitate soil survey mapping, erosion prediction and allocation of agrochemicals for precision management. The objective of this study was to evaluate the relationship between soil spectral signature and surface soil properties in conventionally managed row crop systems. High-resolution RS data were acquired over bare fields in the Coastal Plain, Appalachian Plateau, and Ridge and Valley provinces of Alabama using the Airborne Terrestrial Applications Sensor multispectral scanner. Soils ranged from sandy Kandiudults to fine textured Rhodudults. Surface soil samples (0-1 cm) were collected from 163 sampling points for soil organic carbon, particle size distribution, and citrate dithionite extractable iron content. Surface roughness, soil water content, and crusting were also measured during sampling. Two methods of analysis were evaluated: 1) multiple linear regression using common spectral band ratios, and 2) partial least squares regression. Our data show that thermal infrared spectra are highly, linearly related to soil organic carbon, sand and clay content. Soil organic carbon content was the most difficult to quantify in these highly weathered systems, where soil organic carbon was generally less than 1.2%. Estimates of sand and clay content were best using partial least squares regression at the Valley site, explaining 42-59% of the variability. In the Coastal Plain, sandy surfaces prone to crusting limited estimates of sand and clay content via partial least squares and regression with common band ratios. Estimates of iron oxide content were a function of mineralogy and best accomplished using specific band ratios, with regression explaining 36-65% of the variability at the Valley and Coastal Plain sites, respectively.

MR Neurography of Brachial Plexus at 3.0 T with Robust Fat and Blood Suppression.

PubMed

Wang, Xinzeng; Harrison, Crystal; Mariappan, Yogesh K; Gopalakrishnan, Karthik; Chhabra, Avneesh; Lenkinski, Robert E; Madhuranthakam, Ananth J

2017-05-01

Purpose To develop and evaluate magnetic resonance (MR) neurography of the brachial plexus with robust fat and blood suppression for increased conspicuity of nerves at 3.0 T in clinically feasible acquisition times. Materials and Methods This prospective study was HIPAA compliant, with institutional review board approval and written informed consent. A low-refocusing-flip-angle three-dimensional (3D) turbo spin-echo (TSE) sequence was modified to acquire both in-phase and out-of-phase echoes, required for chemical shift (Dixon) reconstruction, in the same repetition by using partial echoes combined with modified homodyne reconstruction with phase preservation. This multiecho TSE modified Dixon (mDixon) sequence was optimized by using simulations and phantom studies and in three healthy volunteers. The sequence was tested in five healthy volunteers and was evaluated in 10 patients who had been referred for brachial plexopathy at 3.0 T. The images were evaluated against the current standard of care, images acquired with a 3D TSE short inversion time inversion recovery (STIR) sequence, qualitatively by using the Wilcoxon signed-rank test and quantitatively by using the Friedman two-way analysis of variance, with P < .05 considered to indicate a statistically significant difference. Results Multiecho TSE-mDixon involving partial-echo and homodyne reconstruction with phase preservation achieved uniform fat suppression in half the imaging time compared with multiacquisition TSE-mDixon. Compared with 3D TSE STIR, fat suppression, venous suppression, and nerve visualization were significantly improved (P < .05), while arterial suppression was better but not significantly so (P = .06), with increased apparent signal-to-noise ratio in the dorsal nerve root ganglion and C6 nerve (P < .001) with the multiecho TSE-mDixon sequence. Conclusion The multiecho 3D TSE-mDixon sequence provides robust fat and blood suppression, resulting in increased conspicuity of the nerves, in clinically feasible imaging times and can be used for MR neurography of the brachial plexus at 3.0 T. © RSNA, 2016 Online supplemental material is available for this article.

Molecular evolution and phylogenetic analysis of biocontrol genes acquired from SCoT polymorphism of mycoparasitic Trichoderma koningii inhibiting phytopathogen Rhizoctonia solani Kuhn.

PubMed

Gajera, H P; Hirpara, Darshna G; Katakpara, Zinkal A; Patel, S V; Golakiya, B A

2016-11-01

The biocontrol agent Trichoderma (T. harzianum, T. viride, T. virens, T. hamantum, T. koningii, T. pseudokoningii and Trichoderma species) inhibited variably (15.32 - 88.12%) the in vitro growth of Rhizoctonia solani causing root rot in cotton. The T. koningii MTCC 796 evidenced highest (88.12%) growth inhibition of test pathogen followed by T. viride NBAII Tv23 (85.34%). Scanning electron microscopic study confirmed mycoparasitism for MTCC 796 and Tv23 which were capable of completely overgrowing on R. solani by degrading mycelia, coiling around the hyphae with hook-like structures. The antagonists T. harzianum NBAII Th1 and, T. virens NBAII Tvs12 exhibited strong antibiosis and formed 2-4 mm zone of inhibition for 70.28% and 46.62%, respectively growth inhibition of test pathogen. Mycoparasitism is a strong mode of action for biocontrol activity compared with antibiosis. The antagonists Trichoderma strains were performed for start codon targeted (SCoT) polymorphism to acquire biocontrol genes from potent antagonist. The six unique SCoT fragments amplified by genomic DNA of best mycoparasitic antagonist MTCC 796 strain are subjected to DNA sequencing resulted to confirm two functional sequences for activity related to biocontrol genes. The phylogenetic and molecular evolution of functional 824 bp of SCoT-3 (920) and 776 bp of SCoT-6 (806) fragments signify sequence homology with biocontrol genes endochitinase (partial cds of 203 amino acids) and novel hmgR genes (partial cds of 239 amino acids), respectively and the same were annotated and deposited in NCBI GenBank database. The hmgR gene is liable to be express hmg - CoA reductase which is a key enzyme for regulation of terpene biosynthesis and mycoparasitic strains produced triterpenes during antagonism to inhibit growth of fungal pathogen as evidenced with GC-MS profile. The biocontrol genes are found in best antagonist T. koningii MTCC 796 for mycoparasitic activity to restrain the growth of test pathogen R. solani. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-G-JeP1-07: Development of a Programmable Motion Testbed for the Validation of Ultrasound Tracking Algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shepard, A; Matrosic, C; Zagzebski, J

Purpose: To develop an advanced testbed that combines a 3D motion stage and ultrasound phantom to optimize and validate 2D and 3D tracking algorithms for real-time motion management during radiation therapy. Methods: A Siemens S2000 Ultrasound scanner utilizing a 9L4 transducer was coupled with the Washington University 4D Phantom to simulate patient motion. The transducer was securely fastened to the 3D stage and positioned to image three cylinders of varying contrast in a Gammex 404GS LE phantom. The transducer was placed within a water bath above the phantom in order to maintain sufficient coupling for the entire range of simulatedmore » motion. A programmed motion sequence was used to move the transducer during image acquisition and a cine video was acquired for one minute to allow for long sequence tracking. Images were analyzed using a normalized cross-correlation block matching tracking algorithm and compared to the known motion of the transducer relative to the phantom. Results: The setup produced stable ultrasound motion traces consistent with those programmed into the 3D motion stage. The acquired ultrasound images showed minimal artifacts and an image quality that was more than suitable for tracking algorithm verification. Comparisons of a block matching tracking algorithm with the known motion trace for the three features resulted in an average tracking error of 0.59 mm. Conclusion: The high accuracy and programmability of the 4D phantom allows for the acquisition of ultrasound motion sequences that are highly customizable; allowing for focused analysis of some common pitfalls of tracking algorithms such as partial feature occlusion or feature disappearance, among others. The design can easily be modified to adapt to any probe such that the process can be extended to 3D acquisition. Further development of an anatomy specific phantom better resembling true anatomical landmarks could lead to an even more robust validation. This work is partially funded by NIH grant R01CA190298.« less

Nonrigid registration-based coronary artery motion correction for cardiac computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhagalia, Roshni; Pack, Jed D.; Miller, James V.

2012-07-15

Purpose: X-ray computed tomography angiography (CTA) is the modality of choice to noninvasively monitor and diagnose heart disease with coronary artery health and stenosis detection being of particular interest. Reliable, clinically relevant coronary artery imaging mandates high spatiotemporal resolution. However, advances in intrinsic scanner spatial resolution (CT scanners are available which combine nearly 900 detector columns with focal spot oversampling) can be tempered by motion blurring, particularly in patients with unstable heartbeats. As a result, recently numerous methods have been devised to improve coronary CTA imaging. Solutions involving hardware, multisector algorithms, or {beta}-blockers are limited by cost, oversimplifying assumptions aboutmore » cardiac motion, and populations showing contraindications to drugs, respectively. This work introduces an inexpensive algorithmic solution that retrospectively improves the temporal resolution of coronary CTA without significantly affecting spatial resolution. Methods: Given the goal of ruling out coronary stenosis, the method focuses on 'deblurring' the coronary arteries. The approach makes no assumptions about cardiac motion, can be used on exams acquired at high heart rates (even over 75 beats/min), and draws on a fast and accurate three-dimensional (3D) nonrigid bidirectional labeled point matching approach to estimate the trajectories of the coronary arteries during image acquisition. Motion compensation is achieved by employing a 3D warping of a series of partial reconstructions based on the estimated motion fields. Each of these partial reconstructions is created from data acquired over a short time interval. For brevity, the algorithm 'Subphasic Warp and Add' (SWA) reconstruction. Results: The performance of the new motion estimation-compensation approach was evaluated by a systematic observer study conducted using nine human cardiac CTA exams acquired over a range of average heart rates between 68 and 86 beats/min. Algorithm performance was based-lined against exams reconstructed using standard filtered-backprojection (FBP). The study was performed by three experienced reviewers using the American Heart Association's 15-segment model. All vessel segments were evaluated to quantify their viability to allow a clinical diagnosis before and after motion estimation-compensation using SWA. To the best of the authors' knowledge this is the first such observer study to show that an image processing-based software approach can improve the clinical diagnostic value of CTA for coronary artery evaluation. Conclusions: Results from the observer study show that the SWA method described here can dramatically reduce coronary artery motion and preserve real pathology, without affecting spatial resolution. In particular, the method successfully mitigated motion artifacts in 75% of all initially nondiagnostic coronary artery segments, and in over 45% of the cases this improvement was enough to make a previously nondiagnostic vessel segment clinically diagnostic.« less

Immunoglobulin G4-related acquired hemophilia: A case report

PubMed Central

Li, Xiaoyan; Duan, Wei; Zhu, Xiang; Xu, Jianying

2016-01-01

Acquired hemophilia A (AHA) is a relatively rare and life-threatening bleeding disorder whose pathogenesis is not completely understood. The present study reports a rare case of immunogubulin (IgG)4-related AHA with multisystemic involvement. A 55-year old male patient presented with symptoms of bronchial asthma and multiple subdermal hematomas. Chest computed tomography showed multiple diffuse nodular lesions with thickening of bronchovascular bundles, and scattered high-density spots in both lung lobes. Laboratory investigations showed increased activated partial prothrombin time (120.0 sec), a markedly decreased factor VIII (FVIII) activity (0.5%), a high-titer of FVIII inhibitor (27.2 Bethesda units/ml) and a marked increase in serum IgG4 (>4.03 g/l) level. Left inguinal lymph node biopsy revealed capsular thickening with marked lymphoplasmacytic infiltration, occlusive phlebitis and irregular fibrosis. Immunostaining revealed numerous IgG4-positive plasma cells (>100 cells/human plasma fibronectin) in the nodular lesions, with an IgG4/IgG ratio of >40%. The symptoms were markedly alleviated following corticosteroid therapy. The current study presents the first reported case of a rare IgG4-related AHA that presented with unusual clinical features and multisystemic involvement. The patient responded well to corticosteroid therapy. Documentation of such rare cases will help in characterizing the pathogenesis, and prompt recognition and timely treatment of this rare disorder. PMID:28105131

The Ischia volcanic island (Southern Italy): Inferences from potential field data interpretation

NASA Astrophysics Data System (ADS)

Paoletti, V.; Di Maio, R.; Cella, F.; Florio, G.; Motschka, K.; Roberti, N.; Secomandi, M.; Supper, R.; Fedi, M.; Rapolla, A.

2009-01-01

In this paper we present a study of the structural setting of the volcanic island of Ischia by the analysis and interpretation of high-resolution aeromagnetic and self-potential data recently acquired over the island. The magnetic data allowed us to locate the main anomaly sources and lineaments of the island and its offshore surroundings, while the self-potential (SP) data provided information on both the structural pattern of the resurgent caldera and the high-temperature fluid circulation. An inversion of the acquired magnetic and SP data, and a joint modelling of the magnetic data and of a previous gravity data set along a SW-NE profile allowed us to build a model of the island. The model is characterized by the presence of an igneous-very likely trachytic-structure, whose top is located at 1200-1750 m b.s.l. Such a body, possibly formed by several neighbouring intrusions, has a density contrast with the pyroclastic cover of about 0.4 gr/cm 3 and its central-western part, below Mt. Epomeo, seems to be demagnetized. The demagnetization should be connected to the high geothermal gradient measured in this portion of the island and may be due to hydro-chemical alteration processes and/or to the possible presence of partially melted spots within the intrusion. Our outcome is consistent with the results of previous geophysical, geo-volcanological and geothermal studies.

MSP-Tool: a VBA-based software tool for the analysis of multispecimen paleointensity data

NASA Astrophysics Data System (ADS)

Monster, Marilyn; de Groot, Lennart; Dekkers, Mark

2015-12-01

The multispecimen protocol (MSP) is a method to estimate the Earth's magnetic field's past strength from volcanic rocks or archeological materials. By reducing the amount of heating steps and aligning the specimens parallel to the applied field, thermochemical alteration and multi-domain effects are minimized. We present a new software tool, written for Microsoft Excel 2010 in Visual Basic for Applications (VBA), that evaluates paleointensity data acquired using this protocol. In addition to the three ratios (standard, fraction-corrected and domain-state-corrected) calculated following Dekkers and Böhnel (2006) and Fabian and Leonhardt (2010) and a number of other parameters proposed by Fabian and Leonhardt (2010), it also provides several reliability criteria. These include an alteration criterion, whether or not the linear regression intersects the y axis within the theoretically prescribed range, and two directional checks. Overprints and misalignment are detected by isolating the remaining natural remanent magnetization (NRM) and the partial thermoremanent magnetization (pTRM) gained and comparing their declinations and inclinations. The NRM remaining and pTRM gained are then used to calculate alignment-corrected multispecimen plots. Data are analyzed using bootstrap statistics. The program was tested on lava samples that were given a full TRM and that acquired their pTRMs at angles of 0, 15, 30 and 90° with respect to their NRMs. MSP-Tool adequately detected and largely corrected these artificial alignment errors.

Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

NASA Astrophysics Data System (ADS)

Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

2015-08-01

This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800-1800 cm-1) and high-wavenumber (HW)(2800-3600 cm-1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy.

Replicas in Cultural Heritage: 3d Printing and the Museum Experience

NASA Astrophysics Data System (ADS)

Ballarin, M.; Balletti, C.; Vernier, P.

2018-05-01

3D printing has seen a recent massive diffusion for several applications, not least the field of Cultural Heritage. Being used for different purposes, such as study, analysis, conservation or access in museum exhibitions, 3D printed replicas need to undergo a process of validation also in terms of metrical precision and accuracy. The Laboratory of Photogrammetry of Iuav University of Venice has started several collaborations with Italian museum institutions firstly for the digital acquisition and then for the physical reproduction of objects of historical and artistic interest. The aim of the research is to analyse the metric characteristics of the printed model in relation to the original data, and to optimize the process that from the survey leads to the physical representation of an object. In fact, this could be acquired through different methodologies that have different precisions (multi-image photogrammetry, TOF laser scanner, triangulation based laser scanner), and it always involves a long processing phase. It should not be forgotten that the digital data have to undergo a series of simplifications, which, on one hand, eliminate the noise introduced by the acquisition process, but on the other one, they can lead to discrepancies between the physical copy and the original geometry. In this paper we will show the results obtained on a small archaeological find that was acquired and reproduced for a museum exhibition intended for blind and partially sighted people.

Design and Fabrication of a Real-Time Measurement System for the Capsaicinoid Content of Korean Red Pepper (Capsicum annuum L.) Powder by Visible and Near-Infrared Spectroscopy.

PubMed

Lim, Jongguk; Kim, Giyoung; Mo, Changyeun; Kim, Moon S

2015-10-29

This research aims to design and fabricate a system to measure the capsaicinoid content of red pepper powder in a non-destructive and rapid method using visible and near infrared spectroscopy (VNIR). The developed system scans a well-leveled powder surface continuously to minimize the influence of the placenta distribution, thus acquiring stable and representative reflectance spectra. The system incorporates flat belts driven by a sample input hopper and stepping motor, a powder surface leveler, charge-coupled device (CCD) image sensor-embedded VNIR spectrometer, fiber optic probe, and tungsten halogen lamp, and an automated reference measuring unit with a reference panel to measure the standard spectrum. The operation program includes device interface, standard reflectivity measurement, and a graphical user interface to measure the capsaicinoid content. A partial least square regression (PLSR) model was developed to predict the capsaicinoid content; 44 red pepper powder samples whose measured capsaicinoid content ranged 13.45-159.48 mg/100 g by per high-performance liquid chromatography (HPLC) and 1242 VNIR absorbance spectra acquired by the pungency measurement system were used. The determination coefficient of validation (RV2) and standard error of prediction (SEP) for the model with the first-order derivative pretreatment method for Korean red pepper powder were 0.8484 and ±13.6388 mg/100 g, respectively.

Implementation of material decomposition using an EMCCD and CMOS-based micro-CT system.

PubMed

Podgorsak, Alexander R; Nagesh, Sv Setlur; Bednarek, Daniel R; Rudin, Stephen; Ionita, Ciprian N

2017-02-11

This project assessed the effectiveness of using two different detectors to obtain dual-energy (DE) micro-CT data for the carrying out of material decomposition. A micro-CT coupled to either a complementary metal-oxide semiconductor (CMOS) or an electron multiplying CCD (EMCCD) detector was used to acquire image data of a 3D-printed phantom with channels filled with different materials. At any instance, materials such as iohexol contrast agent, water, and platinum were selected to make up the scanned object. DE micro-CT data was acquired, and slices of the scanned object were differentiated by material makeup. The success of the decomposition was assessed quantitatively through the computation of percentage normalized root-mean-square error (%NRMSE). Our results indicate a successful decomposition of iohexol for both detectors (%NRMSE values of 1.8 for EMCCD, 2.4 for CMOS), as well as platinum (%NRMSE value of 4.7). The CMOS detector performed material decomposition on air and water on average with 7 times more %NRMSE, possibly due to the decreased sensitivity of the CMOS system. Material decomposition showed the potential to differentiate between materials such as the iohexol and platinum, perhaps opening the door for its use in the neurovascular anatomical region. Work supported by Toshiba America Medical Systems, and partially supported by NIH grant 2R01EB002873.

Anti-factor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A

PubMed Central

Yoshihashi, Kazutaka; Takeda, Minako; Kitazawa, Takehisa; Soeda, Tetsuhiro; Igawa, Tomoyuki; Sampei, Zenjiro; Kuramochi, Taichi; Sakamoto, Akihisa; Haraya, Kenta; Adachi, Kenji; Kawabe, Yoshiki; Nogami, Keiji; Shima, Midori; Hattori, Kunihiro

2014-01-01

ACE910 is a humanized anti-factor IXa/X bispecific antibody mimicking the function of factor VIII (FVIII). We previously demonstrated in nonhuman primates that a single IV dose of ACE910 exerted hemostatic activity against hemophilic bleeds artificially induced in muscles and subcutis, and that a subcutaneous (SC) dose of ACE910 showed a 3-week half-life and nearly 100% bioavailability, offering support for effective prophylaxis for hemophilia A by user-friendly SC dosing. However, there was no direct evidence that such SC dosing of ACE910 would prevent spontaneous bleeds occurring in daily life. In this study, we newly established a long-term primate model of acquired hemophilia A by multiple IV injections of an anti-primate FVIII neutralizing antibody engineered in mouse-monkey chimeric form to reduce its antigenicity. The monkeys in the control group exhibited various spontaneous bleeding symptoms as well as continuous prolongation of activated partial thromboplastin time; notably, all exhibited joint bleeds, which are a hallmark of hemophilia. Weekly SC doses of ACE910 (initial 3.97 mg/kg followed by 1 mg/kg) significantly prevented these bleeding symptoms; notably, no joint bleeding symptoms were observed. ACE910 is expected to prevent spontaneous bleeds and joint damage in hemophilia A patients even with weekly SC dosing, although appropriate clinical investigation is required. PMID:25274508

Implementation of material decomposition using an EMCCD and CMOS-based micro-CT system

NASA Astrophysics Data System (ADS)

Podgorsak, Alexander R.; Nagesh, S. V. Setlur; Bednarek, Daniel R.; Rudin, Stephen; Ionita, Ciprian N.

2017-03-01

This project assessed the effectiveness of using two different detectors to obtain dual-energy (DE) micro-CT data for the carrying out of material decomposition. A micro-CT coupled to either a complementary metal-oxide semiconductor (CMOS) or an electron multiplying CCD (EMCCD) detector was used to acquire image data of a 3D-printed phantom with channels filled with different materials. At any instance, materials such as iohexol contrast agent, water, and platinum were selected to make up the scanned object. DE micro-CT data was acquired, and slices of the scanned object were differentiated by material makeup. The success of the decomposition was assessed quantitatively through the computation of percentage normalized root-mean-square error (%NRMSE). Our results indicate a successful decomposition of iohexol for both detectors (%NRMSE values of 1.8 for EMCCD, 2.4 for CMOS), as well as platinum (%NRMSE value of 4.7). The CMOS detector performed material decomposition on air and water on average with 7 times more %NRMSE, possibly due to the decreased sensitivity of the CMOS system. Material decomposition showed the potential to differentiate between materials such as the iohexol and platinum, perhaps opening the door for its use in the neurovascular anatomical region. Work supported by Toshiba America Medical Systems, and partially supported by NIH grant 2R01EB002873.

Towards robust identification and tracking of nevi in sparse photographic time series

NASA Astrophysics Data System (ADS)

Vogel, Jakob; Duliu, Alexandru; Oyamada, Yuji; Gardiazabal, Jose; Lasser, Tobias; Ziai, Mahzad; Hein, Rüdiger; Navab, Nassir

2014-03-01

In dermatology, photographic imagery is acquired in large volumes in order to monitor the progress of diseases, especially melanocytic skin cancers. For this purpose, overview (macro) images are taken of the region of interest and used as a reference map to re-localize highly magni ed images of individual lesions. The latter are then used for diagnosis. These pictures are acquired at irregular intervals under only partially constrained circumstances, where patient positions as well as camera positions are not reliable. In the presence of a large number of nevi, correct identi cation of the same nevus in a series of such images is thus a time consuming task with ample chances for error. This paper introduces a method for largely automatic and simultaneous identi cation of nevi in di erent images, thus allowing the tracking of a single nevus over time, as well as pattern evaluation. The method uses a rotation-invariant feature descriptor that uses the local neighborhood of a nevus to describe it. The texture, size and shape of the nevus are not used to describe it, as these can change over time, especially in the case of a malignancy. We then use the Random Walks framework to compute the correspondences based on the probabilities derived from comparing the feature vectors. Evaluation is performed on synthetic and patient data at the university clinic.

Automatic detection and classification of EOL-concrete and resulting recovered products by hyperspectral imaging

NASA Astrophysics Data System (ADS)

Palmieri, Roberta; Bonifazi, Giuseppe; Serranti, Silvia

2014-05-01

The recovery of materials from Demolition Waste (DW) represents one of the main target of the recycling industry and the its characterization is important in order to set up efficient sorting and/or quality control systems. End-Of-Life (EOL) concrete materials identification is necessary to maximize DW conversion into useful secondary raw materials, so it is fundamental to develop strategies for the implementation of an automatic recognition system of the recovered products. In this paper, HyperSpectral Imaging (HSI) technique was applied in order to detect DW composition. Hyperspectral images were acquired by a laboratory device equipped with a HSI sensing device working in the near infrared range (1000-1700 nm): NIR Spectral Camera™, embedding an ImSpector™ N17E (SPECIM Ltd, Finland). Acquired spectral data were analyzed adopting the PLS_Toolbox (Version 7.5, Eigenvector Research, Inc.) under Matlab® environment (Version 7.11.1, The Mathworks, Inc.), applying different chemometric methods: Principal Component Analysis (PCA) for exploratory data approach and Partial Least Square- Discriminant Analysis (PLS-DA) to build classification models. Results showed that it is possible to recognize DW materials, distinguishing recycled aggregates from contaminants (e.g. bricks, gypsum, plastics, wood, foam, etc.). The developed procedure is cheap, fast and non-destructive: it could be used to make some steps of the recycling process more efficient and less expensive.

Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open, randomised controlled trial.

PubMed Central

Chan, R.; Hemeryck, L.; O'Regan, M.; Clancy, L.; Feely, J.

1995-01-01

OBJECTIVE--To see whether there is a difference in outcome between patients treated with oral and intravenous antibiotics for lower respiratory tract infection. DESIGN--Open controlled trial in patients admitted consecutively and randomised to treatment with either oral co-amoxiclav, intravenous followed by oral co-amoxiclav, or intravenous followed by oral cephalosporins. SETTING--Large general hospital in Dublin. PATIENTS--541 patients admitted for lower respiratory tract infection during one year. Patients represented 87% of admissions with the diagnosis and excluded those who were immunocompromised and patients with severe life threatening infection. MAIN OUTCOME MEASURES--Cure, partial cure, extended antibiotic treatment, change of antibiotic, death, and cost and duration of hospital stay. RESULTS--There were no significant differences between the groups in clinical outcome or mortality (6%). However, patients randomised to oral co-amoxiclav had a significantly shorter hospital stay than the two groups given intravenous antibiotic (median 6 v 7 and 9 days respectively). In addition, oral antibiotics were cheaper, easier to administer, and if used routinely in the 800 or so patients admitted annually would lead to savings of around 176,000 pounds a year. CONCLUSIONS--Oral antibiotics in community acquired lower respiratory tract infection are at least as efficacious as intraveous therapy. Their use reduces labour and equipment costs and may lead to earlier discharge from hospital. PMID:7787537

Determination of regional brain temperature using proton magnetic resonance spectroscopy to assess brain-body temperature differences in healthy human subjects.

PubMed

Childs, Charmaine; Hiltunen, Yrjö; Vidyasagar, Rishma; Kauppinen, Risto A

2007-01-01

Proton magnetic resonance spectroscopy ((1)H MRS) was used to determine brain temperature in healthy volunteers. Partially water-suppressed (1)H MRS data sets were acquired at 3T from four different gray matter (GM)/white matter (WM) volumes. Brain temperatures were determined from the chemical-shift difference between the CH(3) of N-acetyl aspartate (NAA) at 2.01 ppm and water. Brain temperatures in (1)H MRS voxels of 2 x 2 x 2 cm(3) showed no substantial heterogeneity. The volume-averaged temperature from single-voxel spectroscopy was compared with body temperatures obtained from the oral cavity, tympanum, and temporal artery regions. The mean brain parenchyma temperature was 0.5 degrees C cooler than readings obtained from three extra-brain sites (P < 0.01). (1)H MRS imaging (MRSI) data were acquired from a slice encompassing the single-voxel volumes to assess the ability of spectroscopic imaging to determine regional brain temperature within the imaging slice. Brain temperature away from the center of the brain determined by MRSI differed from that obtained by single-voxel MRS in the same brain region, possibly due to a poor line width (LW) in MRSI. The data are discussed in the light of proposed brain-body temperature gradients and the use of (1)H MRSI to monitor brain temperature in pathologies, such as brain trauma.

Comparison among T1-weighted magnetic resonance imaging, modified dixon method, and magnetic resonance spectroscopy in measuring bone marrow fat.

PubMed

Shen, Wei; Gong, Xiuqun; Weiss, Jessica; Jin, Ye

2013-01-01

An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods.

Comparison among T1-Weighted Magnetic Resonance Imaging, Modified Dixon Method, and Magnetic Resonance Spectroscopy in Measuring Bone Marrow Fat

PubMed Central

Shen, Wei; Gong, Xiuqun; Weiss, Jessica; Jin, Ye

2013-01-01

Introduction. An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Methods. Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Results. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. Conclusion. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods. PMID:23606951

An evaluation of data-driven motion estimation in comparison to the usage of external-surrogates in cardiac SPECT imaging

PubMed Central

Mukherjee, Joyeeta Mitra; Hutton, Brian F; Johnson, Karen L; Pretorius, P Hendrik; King, Michael A

2014-01-01

Motion estimation methods in single photon emission computed tomography (SPECT) can be classified into methods which depend on just the emission data (data-driven), or those that use some other source of information such as an external surrogate. The surrogate-based methods estimate the motion exhibited externally which may not correlate exactly with the movement of organs inside the body. The accuracy of data-driven strategies on the other hand is affected by the type and timing of motion occurrence during acquisition, the source distribution, and various degrading factors such as attenuation, scatter, and system spatial resolution. The goal of this paper is to investigate the performance of two data-driven motion estimation schemes based on the rigid-body registration of projections of motion-transformed source distributions to the acquired projection data for cardiac SPECT studies. Comparison is also made of six intensity based registration metrics to an external surrogate-based method. In the data-driven schemes, a partially reconstructed heart is used as the initial source distribution. The partially-reconstructed heart has inaccuracies due to limited angle artifacts resulting from using only a part of the SPECT projections acquired while the patient maintained the same pose. The performance of different cost functions in quantifying consistency with the SPECT projection data in the data-driven schemes was compared for clinically realistic patient motion occurring as discrete pose changes, one or two times during acquisition. The six intensity-based metrics studied were mean-squared difference (MSD), mutual information (MI), normalized mutual information (NMI), pattern intensity (PI), normalized cross-correlation (NCC) and entropy of the difference (EDI). Quantitative and qualitative analysis of the performance is reported using Monte-Carlo simulations of a realistic heart phantom including degradation factors such as attenuation, scatter and system spatial resolution. Further the visual appearance of motion-corrected images using data-driven motion estimates was compared to that obtained using the external motion-tracking system in patient studies. Pattern intensity and normalized mutual information cost functions were observed to have the best performance in terms of lowest average position error and stability with degradation of image quality of the partial reconstruction in simulations. In all patients, the visual quality of PI-based estimation was either significantly better or comparable to NMI-based estimation. Best visual quality was obtained with PI-based estimation in 1 of the 5 patient studies, and with external-surrogate based correction in 3 out of 5 patients. In the remaining patient study there was little motion and all methods yielded similar visual image quality. PMID:24107647

Classification of cucumber green mottle mosaic virus (CGMMV) infected watermelon seeds using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Lee, Hoonsoo; Lim, Hyoun-Sub; Cho, Byoung-Kwan

2016-05-01

The Cucumber Green Mottle Mosaic Virus (CGMMV) is a globally distributed plant virus. CGMMV-infected plants exhibit severe mosaic symptoms, discoloration, and deformation. Therefore, rapid and early detection of CGMMV infected seeds is very important for preventing disease damage and yield losses. Raman spectroscopy was investigated in this study as a potential tool for rapid, accurate, and nondestructive detection of infected seeds. Raman spectra of healthy and infected seeds were acquired in the 400 cm-1 to 1800 cm-1 wavenumber range and an algorithm based on partial least-squares discriminant analysis was developed to classify infected and healthy seeds. The classification model's accuracies for calibration and prediction data sets were 100% and 86%, respectively. Results showed that the Raman spectroscopic technique has good potential for nondestructive detection of virus-infected seeds.

Kinetics of wet sodium vapor complex plasma

NASA Astrophysics Data System (ADS)

Mishra, S. K.; Sodha, M. S.

2014-04-01

In this paper, we have investigated the kinetics of wet (partially condensed) Sodium vapor, which comprises of electrons, ions, neutral atoms, and Sodium droplets (i) in thermal equilibrium and (ii) when irradiated by light. The formulation includes the balance of charge over the droplets, number balance of the plasma constituents, and energy balance of the electrons. In order to evaluate the droplet charge, a phenomenon for de-charging of the droplets, viz., evaporation of positive Sodium ions from the surface has been considered in addition to electron emission and electron/ion accretion. The analysis has been utilized to evaluate the steady state parameters of such complex plasmas (i) in thermal equilibrium and (ii) when irradiated; the results have been graphically illustrated. As a significant outcome irradiated, Sodium droplets are seen to acquire large positive potential, with consequent enhancement in the electron density.

Status gelasticus after temporal lobectomy: ictal FDG-PET findings and the question of dual pathology involving hypothalamic hamartomas.

PubMed

Palmini, Andre; Van Paesschen, Wim; Dupont, Patrick; Van Laere, Koen; Van Driel, Guido

2005-08-01

To present the first ictal fluorodeoxyglucose-positron emission tomography (FDG-PET) evidence of the hypothalamic origin of gelastic seizures in a patient with a hypothalamic hamartoma (HH) and to raise the issue of true dual pathology related to this entity. Ictal FDG-PET was acquired during an episode of status gelasticus with preserved consciousness, in a patient previously operated on for complex partial seizures (CPSs) due to a temporal lobe epileptogenic cyst. Ictal hypermetabolism was localized to the region of the HH during the status gelasticus. CPSs had been completely eliminated after temporal lobe surgery. Ictal FDG-PET independently confirmed that gelastic seizures in patients with HH do originate in the diencephalic lesion. An HH may coexist with another epileptogenic lesion, in a context of dual pathology.

Stitching interferometry of a full cylinder without using overlap areas

NASA Astrophysics Data System (ADS)

Peng, Junzheng; Chen, Dingfu; Yu, Yingjie

2017-08-01

Traditional stitching interferometry requires finding out the overlap correspondence and computing the discrepancies in the overlap regions, which makes it complex and time-consuming to obtain the 360° form map of a cylinder. In this paper, we develop a cylinder stitching model based on a new set of orthogonal polynomials, termed Legendre Fourier (LF) polynomials. With these polynomials, individual subaperture data can be expanded as a composition of the inherent form of a partial cylinder surface and additional misalignment parameters. Then the 360° form map can be acquired by simultaneously fitting all subaperture data with the LF polynomials. A metal shaft was measured to experimentally verify the proposed method. In contrast to traditional stitching interferometry, our technique does not require overlapping of adjacent subapertures, thus significantly reducing the measurement time and making the stitching algorithm simple.

Search for the Universal Ancestors

NASA Technical Reports Server (NTRS)

Hartman, H. (Editor); Lawless, J. G. (Editor); Morrison, P. (Editor)

1985-01-01

By its nature, the study of the origins of life is multidisciplinary, requiring contributions from astronomers, biologists, chemists, geologists, physicists, and many others. Partial answers are provided to many questions about organic chemical evolution and the origin of life. It is observed that the gaps in our knowledge concerning the steps from the nonliving to the living are numerous. Among these gaps are: (1) a solar system formation with its accumulation of raw materials; (2) the synthesis of the life forming monomers, such as the amino acids, nucleotides, and lipids; (3) the condensation of these monomers into useful polymers, such as proteins and nucleic acids; (4) the sequestering of these materials into droplets of proteinoid or membrane-like structures; and (5) the development of a chemical memory (the genetic code) to pass on to the progeny the information acquired.