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Unlike many other brands, luxury brands can enjoy remarkably enduring success. This paper presents an interview with a senior executive responsible for marketing Maison Louis Roederer's champagnes, including the legendary Cristal, in the United States for the last 20 years. We explore the differences between luxury and mass-market brands, the role of creative vision, how brands remain relevant through innovation while remaining faithful to their history, and how luxury brands create passionate buyers who seek to be a part of the brand, not simply consumers of the brand. We conclude with a discussion of the implications for market orientation, understanding consumers as fans, and other future research topics. [ABSTRACT FROM AUTHOR]

Context: Somatostatin (SST) and dopamine (DA) inhibit growth hormone (GH) secretion and proliferation of GH-secreting pituitary adenomas (GHomas) through binding to SSTR2 and D2R receptors. Chimeric SST-DA compounds (Dopastatins) display increased potency in inhibiting GH secretion, as compared with individual SST or DA analogs (alone or combined). Objective: To assess the efficacy of a second-generation dopastatin, TBR-065, in suppressing GH secretion from human GH- and GH/prolactin(PRL)-omas. Design: We compared the ability of TBR-065 to inhibit GH secretion from primary cultures of human GH- or GH/PRLoma cells to that of the first generation dopastatin, TBR-760 (formerly BIM-23A760), octreotide (OCT) and cabergoline (CAB), the later either alone or combined. We investigated whether there was any impact of BIM-133, the metabolite of TBR-065, on the ability of TBR-065 to inhibit GH in these cultures. Methods: 17 GH- and GH/PRLomas were included in this study. Inhibition of GH secretion by TBR-065, TBR-760, OCT and CAB (0.1 pM to 0.1 µM) was assessed over a period of 8 h. Results: All tumors expressed SSTR2 and D2R mRNAs. GH suppression was higher with TBR-065 as compared with TBR-760 (Emax = 57 ± 5.6% vs. 41.1 ± 12.5%, respectively, p < 0.001) or with OCT + CAB (Emax = 56.8 ± 7.2% vs. 44.4 ± 9.4%, p < 0.001). BIM-133 did not have any impact on the activity of TBR-065. Conclusion: TBR-065 has significantly improved efficacy in suppressing GH secretion as compared to current available therapies and may represent a new promising option for the treatment of acromegaly. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome due to mutations of the proto-oncogene REarranged during Transfection (RET), defined by the association of medullary thyroid carcinoma (MTC) in almost 100% cases, and pheochromocytoma in roughly 50% (primary hyperparathyroidism can be seen in 10–20% of patients with MEN2A). Early thyroidectomy and the efficacy of novel tyrosine kinase inhibitors modified the natural history of MTC, with possibilities of cure or long-term control. The second main compound, pheochromocytoma, is reported with a variable penetrance, from 10 to 80% cases, depending on the mutation of RET. Pheochromocytoma constitutes the main disease to screen in patients with RET mutations. Pheochromocytoma clinical and biochemical diagnosis, as well as the way to treat it are thus crucial. This review will thus focus on the epidemiological specificities of MEN2-related pheochromocytoma, the genotype/phenotype relationship, the modern imaging modalities necessary to confirm the diagnosis in this hereditary context, as well as the optimal management and the possibilities of adrenal sparing surgery. Additional information will include the natural history of MEN2B-pheochromocytoma, the rare cases of malignant pheochromocytoma, and the factors that could modify the penetrance between individuals carrying the same mutation, especially in the same family. [ABSTRACT FROM AUTHOR]

Satellite Laser Ranging (SLR) began in the mid-1960s on satellites of opportunity with retro-reflectors intended as a part of intercomparison tests of satellite tracking techniques. Shortly thereafter, data from these satellites began to work their way into geodetic solutions and dedicated geodesy experiments. By early 1970s when future requirements for centimeter accuracy were envisioned, planning began for dedicated, spherical retro-reflector geodetic satellites. Built with high mass-to-area ratios, these satellites would have important applications in gravity field modeling, station geolocation and fiducial reference systems, Earth rotation, and fundamental physics. Early geodetic satellites were Starlette, launched in 1975 by Centre National d'Etudes Spatiales (CNES), and LAGEOS in 1976 by the National Aeronautics and Space Administration (NASA). Recent geodetic satellites include LARES, launched in 2012, and LARES-2 under development, both by the Italian Space Agency (ASI). Today, a complex of these 'geodetic satellites' from low to high altitude Earth orbits supports many space geodesy requirements. This paper will discuss the evolution of the geodetic satellites from the early days, through current programs and out to future needs as we approach our goal for millimeter accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Carney complex (CNC) is a rare autosomal dominant syndrome, characterized by mucocutaneous pigmentation, cardiac, cutaneous myxomas and endocrine overactivity. It is generally caused by inactivating mutations in the PRKAR1A (protein kinase cAMP-dependent type I regulatory subunit alpha) gene. Acromegaly is an infrequent manifestation of CNC, reportedly diagnosed in 10% of patients. Methods: We here report the case of a patient who was concomitantly diagnosed with Carney complex, due to a new mutation in PRKAR1A ((NM_002734.3:c.80_83del, p.(Ile27Lysfs*101 in exon 2), and acromegaly. In parallel, we conducted an extensive review of published case reports of acromegaly in the setting of CNC. Results: The 43-year-old patient was diagnosed with an acromegaly due to a GH-secreting pituitary microadenoma resistant to somatostatin analogs. He underwent transsphenoidal surgery in our tertiary referral center, which found a pure GH-secreting adenoma. In the literature, we identified 57 cases (24 men, 33 women) of acromegaly in CNC patients. The median age at diagnosis was 28.8 ± 12 year and there were 6 cases of gigantism. Acromegaly revealed CNC in only 4 patients. 24 patients had a microadenoma and two carried pituitary hyperplasia and/or multiple adenomas, suggesting that CNC may result in a higher proportion of microadenoma as compared to non-CNC acromegaly. Conclusions: Although it rarely reveals CNC, acromegaly is diagnosed at a younger age in this setting, with a higher proportion of microadenomas. [ABSTRACT FROM AUTHOR]

Purpose: Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in pituitary development have been implicated. Congenital CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD. Methods: Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes (PROP1/HESX1/LHX4/LHX3/POU1F1) involved in the pituitary development following an established algorithm. Results: In seven out of 23 patients (30%) a specific mutation in genes encoding pituitary transcription factors was discovered. In five patients, two different mutations of the PROP1 gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the LHX4 gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2. Conclusions: Our study confirms that the two most common mutations of the PROP1 gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of pituitary transcription factor genes are extremely rare. [ABSTRACT FROM AUTHOR]

The Smithsonian Astrophysical Observatory (SAO) and the Centre National d'Études Spatiales (CNES) worked closely together in the early years of the space program to deploy satellite laser ranging (SLR) systems at overseas sites to enhance global coverage to support specific missions. The data were routinely made available for use by the science community for programs in geodesy, gravity field, atmospheric physics, and ultimately for oceanography and geodynamics. SAO and CNES organized campaigns for international participation and loaned each other equipment to enhance the network. SAO and CNES provided technical expertise and advice to a number of other groups as they planned and deployed SLR systems. In this paper, we will discuss the history and the role of the two institutions in the building of the international SLR network. [ABSTRACT FROM AUTHOR]

In recent years, familial pheochromocytoma (PHEO) with germline mutations in the MAX (MYC associated factor X) gene has been reported in a few cases. Here, we investigated a 25-year-old patient with multiple PHEOs associated with a non-sense germline MAX mutation. Preoperative F-FDOPA PET/CT revealed bilateral adrenal involvement with multiple tumors. In addition, both adrenal glands were found to have diffuse or nodular adrenal medullary hyperplasia (AMH), a histopathological feature previously described as a precursor of MEN2- and SDHB-related PHEOs but not MAX. After bilateral adrenalectomy, different paraffin-embedded and frozen samples were analyzed for allelic imbalances of the MAX gene using allelic quantification by pyrosequencing. The expression of the protein MAX was studied by immunohistochemistry. All PHEOs but also nodular AMH exhibited a loss of the normal allele. By contrast, the diffuse AMH did not show loss-of-heterozygosity. Nevertheless, immunohistochemistry demonstrated loss of protein MAX expression in all samples including diffuse hyperplasia, suggesting a causative role of MAX mutation for both PHEOs and AMH. The present case shows that both nodular and diffuse AMH belongs to the spectrum of MAX-related disease. These data support the possible continuum between nodular AMH and PHEO, expanding the qualification of micro-PHEO to nodular AMH. [ABSTRACT FROM AUTHOR]

Purpose: Succinate dehydrogenase B ( SDHB) associated pheochromocytomas (PHEOs) are associated with a higher risk of tumor aggressiveness and malignancy. The aim of the present study was to evaluate (1) the frequency of germline SDHB mutations in apparently sporadic patients with PHEO who undergo preoperative genetic testing and (2) the ability to predict pathogenic mutations. Methods: From 2012 to 2016, 82 patients underwent a PHEO surgical resection. Sixteen were operated in the context of hereditary PHEO and were excluded from analysis. Among the 66 remaining cases, 48 were preoperatively screened for an SDHB mutation. In addition to imaging studies with specific radiopharmaceuticals (I-MIBG or F-FDOPA) for exclusion of multifocality/metastases, 36 patients underwent F-FDG PET/CT. Results: From the 48 genetically screened patients, genetic testing found a germline SDHB variant in two (4.2%) cases: a variant of unknown significance, exon 1, c.14T>G (p.Val5Gly), and a most likely pathogenic mutation, exon 5, c.440A>G (p.Tyr147Cys), according to in silico analysis. Structural and functional analyses of the protein predicted that p.Tyr147Cys mutant was pathogenic. Both tumors exhibited moderate F-FDG PET uptake with similar uptake patterns to non- SDHB mutated PHEOs. The two patients underwent total laparoscopic adrenalectomies. Of the remaining patients, 44 underwent a laparoscopic adrenalectomy, and two had an open approach. Pathological analysis of the tumors from patients bearing two germline SDHB variants revealed a typical PHEO (PASS 0 and 2). Ex-vivo analyses (metabolomics, SDHB immunohistochemistry, loss of heterozygosity analysis) allowed a reclassification of the two SDHB variants as probably non-pathogenic variants. Conclusions: This study illustrates that SDHx mutational analysis can be misleading, even if structural and functional analyses are done. Surgeons should be aware of the difficulty of classifying new SDHB variants prior to implementing SDHB mutation status into a tailored surgical management strategy of a patient. [ABSTRACT FROM AUTHOR]

Purpose: In 2012-2013, a cross-sectional survey was conducted in women visiting a general practitioner for urinary tract infection (UTI), to estimate the annual incidence of UTIs due to antibiotic-resistant Escherichia coli ( E. coli). Methods: A sampling design (stratification, stages and sampling weights) was taken into account in all analyses. Urine analyses were performed for each woman and centralised in one laboratory. Results: Among 538 included women, urine culture confirmed UTI in 75.2 % of cases. E. coli represented 82.8 % of species. Among E. coli, resistance ( I + R) was most common to amoxicillin [38 % (95 % confidence interval 31.1-44.5)] and to trimethoprim/sulfamethoxazole [18.1 % (12.0-24.1)]. Resistance to ciprofloxacin and cefotaxime was lower [1.9 % in both cases, (0.3-3.5)], as it was for nitrofurantoin [0.4 (0-1.0)] and fosfomycin (0). Extended-spectrum β-lactamase (ESBL) represented 1.6 % of E. coli (0.2-2.9). Annual incidence rate of confirmed UTI was estimated at 2400 per 100,000 women (1800-3000). Incidence rates of UTI due to fluoroquinolone-resistant and ESBL-producing E. coli were estimated at 102 per 100,000 women (75-129) and at 32 (24-41), respectively. Conclusions: ESBL had been found in a community population, and even though the rate was low, it represents a warning and confirms that surveillance should continue. [ABSTRACT FROM AUTHOR]

Purpose: Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using Ga-labeled somatostatin analogs (Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene ( SDHB) mutations and head and neck PGLs (HNPGLs). The value of Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare Ga-DOTATATE PET/CT, F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. Design: Ga-DOTATATE, F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. Results: The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for Ga-DOTATATE PET/CT, F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for Ga-DOTATATE PET/CT, F-FDOPA PET/CT, and conventional imaging respectively ( p = 0.042). Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). Conclusion: Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient F-FDOPA. The present study further expands the use of Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. Ga-DOTATATE PET/CT may be inferior to F-FDOPA PET/CT in the detection PHEOs. [ABSTRACT FROM AUTHOR]

Central nervous system hemangioblastomas (CNS-HBs) occur sporadically or as a component of von Hippel-Lindau-VHL syndrome. CNS-HBs share some molecular similarities with pheochromocytomas/paragangliomas (PPGLs) and renal cell carcinomas (RCCs). Recently, hypoxia-inducible factors, particularly somatic HIF2A mutations, have been found to play an important role in the pathogenesis of PPGLs. Somatic mutations in HIF2A have been reported in PPGLs associated with polycythemia, which have been reported to also be present in patients with RCCs and HBs. However, whether CNS-HBs is associated with the presence of a HIF2A mutation is currently uknown. We analyzed somatic HIF2A and VHL mutations in a series of 28 sporadic CNS-HBs. We also investigated the expression of HIF target proteins and hypoxia-associated factor (HAF). Two sporadic CNS-HBs were found to have somatic HIF2A mutations. One tumor had 2 HIF2A missense mutations, one of which was previously described in a PPGL (c.1121 T>A, F374Y). The second patient had coexistence of somatic truncated mutations (c.1669 C>T, Q557*) in HIF2A together with a VHL mutation. Neither of the two patients had polycythemia at the time of diagnosis. We demonstrate that the novel truncated mutation in HIF2A (Q557*) affects HIF-2α prolyl hydroxylation with its reduced ubiquitination but intact transcriptional activity, resulting in an activating effect. Both CNS-HB samples showed positive expression of VEGFR2/CA9/Glut1 and HAF. Our data support the unique central role of the VHL/HIF-2α signaling pathway in the molecular pathogenesis of CNS-HBs and show for the first time the presence of HIF2A mutations in sporadic HB. [ABSTRACT FROM AUTHOR]

Skin plays a protective role against the loss of water and external aggression, including mechanical stresses. These crucial functions are ensured by different cutaneous layers, particularly the stratum corneum (SC). During aging, the human skin reveals some apparent modifications of functionalities such as a loss of elasticity. Our investigations aimed at demonstrating that Raman microspectroscopy, as a label-free technique with a high molecular specificity, is efficient to assess in vivo the molecular composition of the skin and the alterations underwent during aging. Our approach was based on a search for correlation between Raman data collected on healthy female volunteers of different ages (from 21 to 70 years old) by means of a remote confocal Raman and skin firmness measurements used as a reference method. Raman and biometric data were then submitted to a partial least square (PLS)-based data processing. Our experiments demonstrated the potential of Raman microspectroscopy to provide an objective in vivo assessment of the skin 'biological age' that can be very different from the 'chronological age' of the person. In addition, Raman features sensitive to the elasticity and the fatigability of the SC were highlighted. Thereafter, calibration transfer functions were constructed to show the possibility to compare the results obtained during two distinct measurement campaigns conducted with two Raman probes of the same conception. This approach could lead to several interesting prospects, in particular by objectifying the effects of dermocosmetic products on the superficial layers of the skin and by accessing some underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas. To investigate new therapeutic strategies, we evaluated the activity of everolimus (mTOR inhibitor), BKM-120 and BEZ-235 (new Pi3K/Akt/mTOR inhibitors), octreotide and a combined treatment (octreotide plus everolimus), on cell proliferation, signaling pathways, and cell cycle proteins, respectively. The in vitro study was conducted on human meningioma primary cells extracted from fresh tumors, allowing the assessment of somatostatin analogs at the concentration levels used in patients. The results were correlated to WHO grades. Further, everolimus decreased cell viability of human meningiomas, but concomitantly, induced Akt activation, reducing the antiproliferative effect of the drug. The new Pi3K inhibitors were not more active than everolimus alone, limiting their clinical relevance. In contrast, a clear cooperative inhibitory effect of octreotide and everolimus was observed on cell proliferation in all tested meningiomas, including WHO grades II-III. Octreotide not only reversed everolimus-induced Akt phosphorylation but also displayed additive and complementary effects with everolimus on downstream proteins involved in translation (4EB-P1), and controlling cell cycle (p27Kip1 and cyclin D1). We have demonstrated a co-operative action between everolimus and octreotide on cell proliferation in human meningiomas, including aggressive ones, establishing the basis for a clinical trial. [ABSTRACT FROM AUTHOR]

Pseudohypoparathyroidism is a rare endocrine disorder that can be caused by genetic (mainly maternally inherited inactivating point mutations, although intragenic and gross deletions have rarely been reported) or epigenetic alterations at GNAS locus. Clinical and molecular characterization of this disease is not that easy because of phenotypic, biochemical and molecular overlapping features between both subtypes of the disease. The European Consortium for the study of PHP (EuroPHP) designed the present work with the intention of generating the standards of diagnostic clinical molecular (epi)genetic testing in PHP patients. With this aim, DNA samples of eight independent PHP patients carrying GNAS genetic and/or epigenetic defects (three patients with GNAS deletions, two with 20q uniparental disomy and three with a methylation defect of unknown origin) without GNAS point mutations were anonymized and sent to the five participant laboratories for their routine genetic analysis (methylation-specific (MS)-MLPA, pyrosequencing and EpiTYPER) and interpretations. All laboratories were able to detect methylation defects and, after the data analysis, the Consortium compared the results to define technical advantages and disadvantages of different techniques. To conclude, we propose as first-level investigation in PHP patients copy number and methylation analysis by MS-MLPA. Then, in patients with partial methylation defect, the result should be confirmed by single CpG bisulphite-based methods (ie pyrosequencing), whereas in case of a complete methylation defect without detectable deletion, microsatellites or SNP genotyping should be performed to exclude uniparental disomy 20. [ABSTRACT FROM AUTHOR]

Tahiti is a unique geodetic site located in the south Pacific Ocean where few observatories exist nearby. The American mobile station MOBLAS-8 was installed in Tahiti in 1998, and GPS and DORIS systems were also deployed in its vicinity in order to develop this site into one of the fundamental colocated sites of the International Terrestrial Reference Frame. In order to make a new estimate of the colocation differences between the different techniques, a campaign of the French Transportable Laser Ranging System (FTLRS) was conducted in Tahiti between April and October 2011. The FTLRS was deployed close to the existing equipment. Observations for LAGEOS 1, LAGEOS 2 and Starlette were studied, and the solutions to the local ties between FTLRS, MOBLAS-8, DORIS and GPS were evaluated. Our results of the geodetic local-ties between laser stations and GPS agree well with the measurements made by the Institut National de l'Information Géographique et Forestière (IGN) during the campaign, with differences less than 2 mm in the vertical direction. The laser station range biases as a function of satellites are also presented, $$-3$$ ( $$\pm $$ 2) mm for MOBLAS-8 and 3 ( $$\pm $$ 3) mm for FTLRS, respectively. In addition, we investigated the role of time bias (ranging from a few hundreds of nanoseconds to one microsecond) given by the Time Transfer by Laser Link experiment, which shows a limited impact on the present SLR analysis. We also compared the coordinates of the three available techniques at Tahiti, i.e., laser, GPS and DORIS. We found the accuracy of laser solutions still needs to be improved, so that the SLR at Tahiti could contribute more effectively to the tracking of satellites and thus to the international reference frame. This study is useful in evaluating the SLR and other space techniques in order to prepare the deployment of new equipment in Tahiti in the near future. [ABSTRACT FROM AUTHOR]

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis. [ABSTRACT FROM AUTHOR]

In familial cases of combined pituitary hormone deficiency the most common mutations are that of Prophet of Pit 1 (PROP1) gene. PROP1 mutations are associated with deficiencies of growth hormone, thyrotropin, prolactin, and gonadotropins (follicle-stimulating hormone and luteinizing hormone), with evolving adrenocorticotropin (ACTH) deficiency in some cases. On imaging in most patients the pituitary gland is hypoplastic, but occasionally transient pituitary enlargement is found. We report a 22-year-old female initially diagnosed at age 12 with familial hypopituitarism due to PROP1 mutation, who presented with coma and respiratory arrest (acute hyponatremia). She was urgently treated in Intensive Care Unit of Emergency Center with hypertonic saline and stress doses of hydrocortisone, which resulted in the fast increase of plasma osmolality resulting in the osmotic demyelination syndrome. Simultaneously and incidentally on computed tomography scan a large sellar and suprasellar mass were reported as possible Rathke's cleft cyst or craniopharyngioma. Once the patient was stable, ACTH deficiency was documented. She remained replaced with hydrocortisone and subsequently underwent transphenoidal surgery. The removed sellar content revealed no pituitary adenoma or pituitary cells, but only an eosinophilic, colloid-like mass, and necrotic acellular debris. Her sister with hypopituitarism had an empty sella. Genetic testing in both sisters revealed the same homozygous c.150delA mutation in PROP1 gene. Here we report two sisters with the same PROP1 mutation who presented in adulthood with different pituitary morphology, one of them with a large sellar and suprasellar mass, in which transphenoidal surgery provided an extremely rare opportunity for a histopathological analysis of the sellar content. Due to the lack of endocrine care during the transition period hypocortisolism which evolved, a consequence of PROP1 mutation, was not recognized. Empirical use of hydrocortisone in the Intensive Care in our patient with life-threatening acute hyponatremia was appropriate but because glucocorticoid therapy on its own corrects hyponatremia even after stopping hypertonic saline infusion, the risk for over-correction of hyponatremia in ACTH deficiency is high. [ABSTRACT FROM AUTHOR]

Idiopathic pituitary insufficiency (IPI) is diagnosed in 10% of all hypopituitary patients. There are several known and unknown aetiologies within the IPI group. The aim of this study was to investigate an adult IPI population for genetic cause according a screening schedule. From files of 373 GH deficient (GHD) patients on GH replacement 50 cases with IPI were identified. Of the 39 patients that approved to the study, 25 patients were selected for genetic investigation according to phenotype and 14 patients were not further tested, as sporadic isolated GHD (n = 9) and GHD with diabetes insipidus (n = 5) have low probability for a known genetic cause. Genotyping of all coding exons of HESX1, LHX4, PROP1, POU1F1 and GH1 genes were performed according to a diagnostic algorithm based on clinical, hormonal and neuroradiological phenotype. Among the 25 patients, an overall rate of 8% of mutations was found, and a 50% rate in familial cases. Among two sibling pairs, one pair that presented with complete anterior pituitary insufficiency, had a compound heterozygous PROP1 gene mutation (codons 117 and 120: exon 3 p Phe 117 Ile (c349 T>A) and p Arg 120 Cys (c358 C>T)) with a phenotype of very late onset ACTH-insufficiency. In the other sibling pair and in the sporadic cases no mutation was identified. This study suggests that currently known genetic causes are rare in sporadic adult IPI patients, and that systematic genetic screening is not needed in adult-onset sporadic cases of IPI. Conversely, familial cases are highly suspect for genetic causes. [ABSTRACT FROM AUTHOR]

The phenotypic heterogeneity of low-grade gliomas (LGGs) is still inconsistently explained by known molecular abnormalities in patients treated according to the present standards of care. IDH1 codon 132 and IDH2 codon 172 sequencing was performed in a series of 47 LGGs and correlated with clinical presentation, MR imaging characteristics, genomic profile and outcome. A total of 38 IDH1 mutations at codon 132 and 2 IDH2 mutations at codon 172 were found, including 35 R132H (87.5%), 2 R132C (5.0%), 1 R132S (2.5%) and 2 R172 M (5%). The IDH mutations were significantly associated with 1p19q deleted genotype ( P = 0.031) and p53 expression ( P = 0.014). The presence (vs. absence) of IDH mutations was associated with a better outcome (5-year survival rate, 93% vs. 51%, respectively, P = 0.000001). After adjustment for age, tumor location and size, radiologic infiltration pattern and extent of surgery, multivariate analysis confirmed that IDH mutations was an independent favorable prognostic factor (hazard ratio = 40.9; 95% CI, 2.89-578.49, P = 0.006). Furthermore, we showed that patients with IDH-nonmutated tumors were significantly older ( P = 0.020) and that these tumors involved significantly more frequently the insula ( P = 0.004), were larger in size (>6 cm, P = 0.047), displayed an infiltrative pattern on MRI ( P = 0.007) and were all p53 negative with no 1p19q deletion ( P < 10). The absence of IDH mutations in LGGs identifies a novel entity of LGGs with distinctive location, infiltrative behavior, specific molecular alterations, and dismal outcome. These findings could significantly modify the LGG classification and may represent a new tool to guide patient-tailored therapy. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence of succinate dehydrogenase (SDH) B, C, and D germline mutations in a surgical series of cervical paragangliomas and to precise the characteristics of patients presenting with familial form. Among 29 patients operated on cervical paragangliomas (carotid or vagal body) at our institution between 1994 and 2007, 23 could be asked for a genetic analysis and a familial study. Clinical characteristics of patients harboring a germline SDH mutation were studied and compared with those presenting without mutation. Mutations were found in 8/23 (35%) patients, mostly in SDHD gene (6 cases), and in SDHB and SDHC gene, respectively, in one case each. Mean age at onset was significantly lower for patients with mutation (34 vs. 51.5 years, P = 0.01). In patients presenting with a mutation, 50% had a family history of paraganglioma compared with 0% for others ( P = 0.008) and 87.5% had a multifocal form of paragangliomas versus 0% for others ( P = 0.001). No difference was found concerning malignant forms between the two groups (12.5 vs. 13.3%). In the 16 patients who had an apparently sporadic paraganglioma, 6% had mutations in the SDH gene. A positive family history of paraganglioma and/or the presence of bilateral or multiple paragangliomas and/or an early age of onset are the main parameters associated with SDH mutations. Genetic testing should be considered for all patients with a cervical paraganglioma, even for those presenting with an apparently sporadic tumor as familial form may be such identified in 6% of cases. [ABSTRACT FROM AUTHOR]

The Western Alps are among the best studied collisional belts with both detailed structural mapping and also crustal geophysical investigations such as the ECORS and EGT seismic profile. By contrast, the present-day kinematics of the belt is still largely unknown due to small relative motions and the insufficient accuracy of the triangulation data. As a consequence, several tectonic problems still remain to be solved, such as the amount of N–S convergence in the Occidental Alps, the repartition of the deformation between the Alpine tectonic units, and the relation between deformation and rotation across the Alpine arc. In order to address these problems, the GPS ALPES group, made up of French, Swiss and Italian research organizations, has achieved the first large-scale GPS surveys of the Western Alps. More than 60 sites were surveyed in 1993 and 1998 with a minimum observation of 3 days at each site. GPS data processing has been done by three independent teams using different software. The different solutions have horizontal repeatabilities (N–E) of 4–7 mm in 1993 and 2–3 mm in 1998 and compare at the 3–5-mm level in position and 2-mm/yr level in velocity. A comparison of 1993 and 1998 coordinates shows that residual velocities of the GPS marks are generally smaller than 2 mm/yr, precluding a detailed tectonic interpretation of the differential motions. However, these data seem to suggest that the N–S compression of the Western Alps is quite mild (less than 2 mm/yr) compared to the global convergence between the African and Eurasian plate (6 mm/yr). This implies that the shortening must be accomodated elsewhere by the deformation of the Maghrebids and/or by rotations of Mediterranean microplates. Also, E–W velocity components analysis supports the idea that E–W extension exists, as already suggested by recent structural and seismotectonic data interpretation. [ABSTRACT FROM AUTHOR]

The International GLONASS Experiment (IGEX-98) was carried out between 19 October 1998 and 19 April 1999. Among several objectives was the precise orbit determination of GPS and GLONASS satellites and its validation by laser ranging observations. Local laser-based orbit corrections (radial, tangential and normal components in a rotating orbital local reference frame) are computed using a geometrical short-arc technique. The order of magnitude of these corrections is at the level of few decimeters, depending on the considered components. The orbit corrections are analyzed as a function of several parameters (date, orbital plane, geographical area). The mean corrections are at the level of several centimeters. However, when averaging over the entire campaign and for all the satellites, no mean radial, tangential and normal orbit corrections are found. The origin of the observed corrections is considered (errors due to the geocentric gravitational constant, the non-gravitational forces, the thermal equilibrium of on-board equipment, the reference systems, the location and the signature of the retroreflector array, and the precision of the satellite laser ranges). Some features are also due to errors in the radio-tracking GLONASS orbits. Further investigations will be needed to better understand the origin of various biases. [ABSTRACT FROM AUTHOR]

Satellite laser ranging (SLR) has proven avery efficient method for contributingto the tracking of altimetric satellites anddetermining accurately their orbitalthough hampered by the non-worldwide coverageand the meteorologicalconditions. Indeed, in some cases it is the onlymethod available to determinethe satellite orbit (e.g., the orbits of the ERS-1and Geosat-Follow-On missions).Moreover, any operational and non-weather dependenttechniques, like GPS,DORIS, PRARE, can exhibit systematic errors inpositioning and orbitography. Acomparison with SLR results allows to evidence sucherrors and vice versa. Fordoing that, two different approaches for determiningprecise orbits can beconsidered: one based on global orbit determination,the other on a short-arctechnique used to locally improve a global orbitdetermined by another trackingtechniques, such as DORIS or GPS. We can thusvalidate a global orbit andachieve orbit quality control to a level of2 to 3 centimeters at present and expectto achieve a level of 1 to 2 centimeters inthe near future. Errors induced bystation coordinates or by the gravity field(geographically correlated errors, forexample) can be estimated from SLR tracking data.Colocation experiments withdifferent techniques in the same geodetic siteplay also a key role to ensure preciserelationships between the geodetic referenceframes linked to each technique. Inparticular, the role of the SLR technique is tostrengthen the vertical component(including velocity) of the positioning, whichis crucial for altimetry missions. The role of SLR data in the modelling of the firstterms of the gravity field has finally to be emphasized,which is of primary importance in orbitography,whatever the tracking technique used.Another application of SLR technology is thesatellite altimeter calibration. Examples of past calibrationand future experiments are given, including theaccuracy we can expect from the Jason-1 and EnviSatspace oceanography missions. [ABSTRACT FROM AUTHOR]

The French Transportable Laser Ranging Station (FTLRS)is a highly mobile satellite laserranging (SLR) system dedicated to the trackingof geodetic satellites equipped withretroreflectors. This station weighs only 300kg witha 13-cm diameter telescope and is housedin eight containers. The reliability of such a station and its accuracy of 2 cmin real field experiment conditionswere demonstrated during a first field campaign carried outfrom October 1996 to February1997 near Ajaccio on Corsica Island, France. The results ofthis probatory experiment suggestedthat several technical improvements and some modificationswere necessary for JASON-1validation and calibration phase and for new applicationssuch as the Time Transfer by LaserLink (T2L2) experiment. A first change concerns theuse of a new laser wavelength (green instead ofinfrared) and of a new avalanche photodiode with atime walk compensation system. Anotherchange is the installation of a coaxial cabletransmitting directly the signal coming from thereturn detector. Finally, a new calibration systemwas developed with several other changes.A short description of the system is first given.Then, the major changes and the main resultsof ground accuracy tests are summarized and presented. [ABSTRACT FROM AUTHOR]

The Drag Temperature Model (1978) has been improved to respond better to the actual requirements of space geodesy, especially under extreme solar and geomagnetic conditions. Extended data and an improved algorithm have been considered, leading to valuable improvements. Temporal variations of temperature of the thermopause, total density and major chemical constituent density are reviewed and compared to the DTM94, DTM78 and MSIS86 models. A comparison with data is performed, giving the mean ratios between observed and model values with their root mean squares for different physical and geometric conditions. This comparison is made for the three models and includes data used in the modelling as well as external data. The limits of the thermosphere modelling are discussed. [ABSTRACT FROM AUTHOR]

GFZ Potsdam and GRGS Toulouse/Grasse jointly developed a new pair of global models of the Earth's gravity field to satisfy the requirements of the recent and future geodetic and altimeter satellite missions. A precise gravity model is a prerequisite for precise satellite orbit restitution, tracking station positioning and altimeter data reduction. According to different applications envisaged, the new model exists in two parallel versions: the first one being derived exclusively from satellite tracking data acquired on 34 satellites, the second one further incorporating satellite altimeter data over the oceans and terrestrial gravity data. The most recent “satellite-only” gravity model is labelled GRIM4-S4 and the “combined” gravity model GRIM4-C4. The models are solutions in spherical harmonics and have a resolution up to degree and order 60 plus a few resonance terms in the case of GRIM4-S4, and up to degree/order 72 in the case of GRIM4-C4, corresponding to a spatial resolution of 555 km at the Earth's surface. The gravitational coefficients were estimated in a rigorous least squares adjustment simultaneously with ocean tidal terms and tracking station position parameters, so that each gravity model is associated with a consistent ocean tide model and a terrestrial reference frame built up by over 300 optical, laser and Doppler tracking stations. Comprehensive quality tests with external data and models, and test arc computations over a wide range of satellites have demonstrated the state-of-the-art capabilities of both solutions in long-wavelength geoid representation and in precise orbit computation. [ABSTRACT FROM AUTHOR]

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Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1.We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGGAAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL. [ABSTRACT FROM AUTHOR]

Cette expérience montre que la Géodésie locale, par méthode Doppler, est possible, c'est-à-dire que ne disposant que de peu de stations, il est possible de les relier géodésiquement entre elles; dans le cas de deux stations assez éloignées, la précision paraît toutefois un peu faible du point de vue géodésique (40 m); par contre, comme l'ont montré les expériences 'Diadèmes', avec trois stations correctement disposées, la précision est bien meilleure, proche du décamètre. (P. CHASSAING, 1969 [6]). Dans ce dernier cas, on a même une excellente information sur la position du centre de gravité de la Terre, ce que nous n'avons pu obtenir. La Géodésie locale par mesure Doppler n'est toutefois possible qu'avec des observations de grandes qualités, de longs passages continus d'un horizon à un autre et un filtrage adéquat des observations. Cet aspect est un des points les plus importants de l'étude. Nous recoupons des résultats trouvés par YIONOULIS, GUIER et NEWTON [5] Enfin, nous avons abservé un écart significatif par rapport à la détermination faite par méthode classique par H.M. DUFOUR. Pour ce faire, Dufour a utilisé les déviations de la verticale déduites de données du Brigadier Bomford. Il estime que la précision n'est pas supérieure à 30 ou 40 mètres. L'écart trouvé ne pose donc pas de problèmes théoriques. Il prouve que, dans certains cas, la Géodésie a encore besoin de points dont la précision est de l'ordre de 30 mètres. [ABSTRACT FROM AUTHOR]

Copyright of Space Science Reviews is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]