Pre‐ and postoperative 68Ga‐DOTATOC positron emission tomography for hormone‐secreting pituitary neuroendocrine tumors

Objectives: Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with 68Ga-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, 68Ga-DOTATOC, in patients with hormone-producing PitNETs before and after surgery. Design/Methods: This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre- and postoperatively with 68Ga-DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression. Results: Thyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4-60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6-9.3) than normal pituitary gland (SUVmax 13.8; 12.1-15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6-19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P 13.8. Conclusions: 68Ga-DOTATOC PET can be used to detect thyrotroph tumours in the pre- and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited

Lower 68 Ga-DOTATOC Uptake in Non-Functioning Pituitary Neuroendocrine Tumors Compared to Normal Pituitary Gland - a Proof-of-Concept Study

OBJECTIVES: 68 Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of 68 Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of 68 Ga-DOTATOC PET in the most common PitNET, i.e. non-functioning (NF)-PitNET. DESIGN/METHODS: NF-PitNET patients (n = 9) and controls (n = 13) were examined preoperatively with 68 Ga-DOTATOC PET for 45 min after tracer injection in dynamic list mode. Tumor specimens were collected during surgery in patients. MRI and PET images were co-registered using PMOD software. The maximum standard uptake value (SUVmax ) was analyzed in manually outlined regions of interest (ROC) around the tumor in patients and around the pituitary gland in controls. Immunohistochemical analyses were conducted on tumor specimens for assessment of tumor cell type and SSTR expression. RESULTS: Median SUVmax (IQR) was lower in patients than in controls (3.9 [3.4-8.5] vs 14.1 [12.5-15.9]; P < .01]. In ROC analysis, the area under the curve was 0.87 (P < .01) for SUVmax , with 78% sensitivity and 92% specificity. Immunohistochemical analysis showed NF-PitNETs were of gonadotroph (n = 7) and corticotroph (n = 2) origin. SSTR expression was high for SSTR3, low-to-moderate for SSTR2, and low for SSTR1 and SSTR5. CONCLUSIONS: This proof-of-concept study shows that 68 Ga-DOTATOC PET can be used to differentiate between normal pituitary tissue and NF-PitNET

Tracing winter temperatures over the last two millennia using a north-east Atlantic coastal record

We present 2500 years of reconstructed bottom water temperatures (BWT) using a fjord sediment archive from the north-east Atlantic region. The BWT represent winter conditions due to the fjord hydrography and the associated timing and frequency of bottom water renewals. The study is based on a ca. 8&thinsp;m long sediment core from Gullmar Fjord (Sweden), which was dated by 210Pb and AMS 14C and analysed for stable oxygen isotopes (δ18O) measured on shallow infaunal benthic foraminiferal species Cassidulina laevigata d'Orbigny 1826. The BWT, calculated using the palaeotemperature equation from McCorkle et al. (1997), range between 2.7 and 7.8&thinsp;°C and are within the annual temperature variability that has been instrumentally recorded in the deep fjord basin since the 1890s. The record demonstrates a warming during the Roman Warm Period ( ∼ 350&thinsp;BCE–450&thinsp;CE), variable BWT during the Dark Ages ( ∼ 450–850&thinsp;CE), positive BWT anomalies during the Viking Age/Medieval Climate Anomaly ( ∼ 850–1350&thinsp;CE) and a long-term cooling with distinct multidecadal variability during the Little Ice Age ( ∼ 1350–1850&thinsp;CE). The fjord BWT record also picks up the contemporary warming of the 20th century (presented here until 1996), which does not stand out in the 2500-year perspective and is of the same magnitude as the Roman Warm Period and the Medieval Climate Anomaly.</p

Anthropogenic and climatic impacts on a coastal environment in the Baltic Sea over the last 1000 years

Coastal environments have experienced large ecological changes as a result of human activities over the last 100-200 years. To understand the severity and potential consequences of such changes, paleoenvironmental records provide important contextual information. The Baltic Sea coastal zone is naturally a vulnerable system and subject to significant human-induced impacts. To put the recent environmental degradation in the Baltic coastal zone into a long-term perspective, and to assess the natural and anthropogenic drivers of environmental change, we present sedimentary records covering the last 1000 years obtained from a coastal inlet (Gasfjarden) and a nearby lake (Lake Storsjon) in Sweden. We investigate the links between a pollen-based land cover reconstruction from Lake Storsjon and paleoenvironmental variables from Gasfjarden itself, including diatom assemblages, organic carbon (C) and nitrogen (N) contents, stable C and N isotopic ratios, and biogenic silica contents. The Lake Storsjon record shows that regional land use was characterized by small-scale agricultural activity between 900 and 1400 CE, which slightly intensified between 1400 and 1800 CE. Substantial expansion of cropland was observed between 1800 and 1950 CE, before afforestation between 1950 and 2010 CE. From the Gasfjarden record, prior to 1800 CE, relatively minor changes in the diatom and geochemical proxies were found. The onset of cultural eutrophication in Gasfjarden can be traced to the 1800s and intensified land use is identified as the main driver. Anthropogenic activities in the 20th century have caused unprecedented ecosystem changes in the coastal inlet, as reflected in the diatom composition and geochemical proxies. (c) 2018 Elsevier Ltd. All rights reserved.Peer reviewe

On the Convergence of Kergin and Hakopian Interpolants at Leja Sequences for the Disk

We prove that Kergin interpolation polynomials and Hakopian interpolation polynomials at the points of a Leja sequence for the unit disk $D$ of a sufficiently smooth function $f$ in a neighbourhood of $D$ converge uniformly to $f$ on $D$. Moreover, when $f$ is $C^\infty$ on $D$, all the derivatives of the interpolation polynomials converge uniformly to the corresponding derivatives of $f$

Acute interaction between hydrocortisone and insulin alters the plasma metabolome in humans

With the aim of identifying biomarkers of glucocorticoid action and their relationship with biomarkers of insulin action, metabolomic profiling was carried out in plasma samples from twenty healthy men who were administered either a low or medium dose insulin infusion (n = 10 each group). In addition, all subjects were given metyrapone (to inhibit adrenal cortisol secretion) +/-hydrocortisone (HC) in a randomised crossover design to produce low, medium and high glucocorticoid levels. The clearest effects of insulin were to reduce plasma levels of the branched chain amino acids (BCAs) leucine/isoleucine and their deaminated metabolites, and lowered free fatty acids and acylcarnitines. The highest dose of hydrocortisone increased plasma BCAs in both insulin groups but increased free fatty acids only in the high insulin group, however hydrocortisone did not affect the levels of acyl carnitines in either group. The clearest interaction between HC and insulin was that hydrocortisone produced an elevation in levels of BCAs and their metabolites which were lowered by insulin. The direct modulation of BCAs by glucocorticoids and insulin may provide the basis for improved in vivo monitoring of glucocorticoid and insulin action

Genetic signs of multiple colonization events in Baltic ciscoes with radiation into sympatric spring- and autumn-spawners confined to early postglacial arrival

Presence of sympatric populations may reflect local diversification or secondary contact of already distinct forms. The Baltic cisco (Coregonus albula) normally spawns in late autumn, but in a few lakes in Northern Europe sympatric autumn and spring- or winter-spawners have been described. So far, the evolutionary relationships and taxonomic status of these main life history forms have remained largely unclear. With microsatellites and mtDNA sequences, we analyzed extant and extinct spring- and autumn-spawners from a total of 23 Swedish localities, including sympatric populations. Published sequences from Baltic ciscoes in Germany and Finland, and Coregonus sardinella from North America were also included together with novel mtDNA sequences from Siberian C.sardinella. A clear genetic structure within Sweden was found that included two population assemblages markedly differentiated at microsatellites and apparently fixed for mtDNA haplotypes from two distinct clades. All sympatric Swedish populations belonged to the same assemblage, suggesting parallel evolution of spring-spawning rather than secondary contact. The pattern observed further suggests that postglacial immigration to Northern Europe occurred from at least two different refugia. Previous results showing that mtDNA in Baltic cisco is paraphyletic with respect to North American C.sardinella were confirmed. However, the inclusion of Siberian C.sardinella revealed a more complicated pattern, as these novel haplotypes were found within one of the two main C.albula clades and were clearly distinct from those in North American C.sardinella. The evolutionary history of Northern Hemisphere ciscoes thus seems to be more complex than previously recognized

A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in wistar rats

A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4 triggers feedback activation of the thyroid hormone system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events

Data descriptor: a global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. (TABLE) Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike