Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible ...evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.
Employment has become increasingly precarious in developed countries, meaning that, for many young adults, jobs provide neither benefits nor security, more work is part time, and employers are ...increasingly hiring workers from temporary help agencies and contract companies rather than as employees of their own company. These changes in employment relations have profound effects on gender roles and on family transitions of young adults, especially young men and in particular in countries such as Japan, where there are rigid family norms and the male-breadwinner tradition still prevails. The authors examined the effects of the experience of non-regular work on the timing of marriage and whether this differs by sex. Using recent life history data from Japan, they found that men working in non-regular jobs are especially likely to postpone marriage. The implications of the growth of precarious work for changes in work and family institutions in Japan are discussed.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
Abstract
As the key enzyme of bacterial nitrogen assimilation, glutamine synthetase (GS) is tightly regulated. In cyanobacteria, GS activity is controlled by the interaction with inactivating protein ...factors IF7 and IF17 encoded by the genes gifA and gifB, respectively. We show that a glutamine-binding aptamer within the gifB 5′ UTR of Synechocystis sp. PCC 6803 is critical for the expression of IF17. Binding of glutamine induced structural re-arrangements in this RNA element leading to enhanced protein synthesis in vivo and characterizing it as a riboswitch. Mutagenesis showed the riboswitch mechanism to contribute at least as much to the control of gene expression as the promoter-mediated transcriptional regulation. We suggest this and a structurally related but distinct element, to be designated type 1 and type 2 glutamine riboswitches. Extended biocomputational searches revealed that glutamine riboswitches are exclusively but frequently found in cyanobacterial genomes, where they are primarily associated with gifB homologs. Hence, this RNA-based sensing mechanism is common in cyanobacteria and establishes a regulatory feedback loop that couples the IF17-mediated GS inactivation to the intracellular glutamine levels. Together with the previously described sRNA NsiR4, these results show that non-coding RNA is an indispensable component in the control of nitrogen assimilation in cyanobacteria.
In the summer of 1845, under the command of Sir John Franklin, 128 officers and men aboard Royal Navy ships HMS Erebus and HMS Terror sailed into Lancaster Sound and entered the waters of Arctic ...North America. The goal of this expedition was to complete the discovery of a northwest passage by navigating the uncharted area between Barrow Strait and Simpson Strait. Franklin and his crew spent the first winter at Beechey Island, where three crewmen died and were buried. In September 1846, the ships became stranded in ice off the northwest coast of King William Island, where they remained until April 1848. At that time, the crew, reduced to 105, deserted the ships and retreated south along the island's western and southern shores in a desperate attempt to reach the mainland and via the Back River, to obtain aid at a Hudson's Bay Company Post. Sadly, not one individual survived. Previous analyses of bone, hair, and soft tissue samples from expedition remains found that crewmembers' tissues contained elevated lead (Pb) levels, suggesting that Pb poisoning may have contributed to their demise; however, questions remain regarding the timing and degree of exposure and, ultimately, the extent to which the crewmembers may have been impacted. To address this historical question, we investigated three hypotheses. First, if elevated Pb exposure was experienced by the crew during the expedition, we hypothesized that those sailors who survived longer (King William Island vs. Beechey Island) would exhibit more extensive uptake of Pb in their bones and vice versa. Second, we hypothesized that Pb would be elevated in bone microstructural features forming at or near the time of death compared with older tissue. Finally, if Pb exposure played a significant role in the failure of the expedition we hypothesized that bone samples would exhibit evidence of higher and more sustained uptake of Pb than that of a contemporary comparator naval population from the 19th century. To test these hypotheses, we analyzed bone and dental remains of crew members and compared them against samples derived from the Royal Navy cemetery in Antigua. Synchrotron-based high resolution confocal X-ray fluorescence imaging was employed to visualize Pb distribution within bone and tooth microstructures at the micro scale. The data did not support our first hypothesis as Pb distribution within the samples from the two different sites was similar. Evidence of Pb within skeletal microstructural features formed near the time of death lent support to our second hypothesis but consistent evidence of a marked elevation in Pb levels was lacking. Finally, the comparative analysis with the Antigua samples did not support the hypothesis that the Franklin sailors were exposed to an unusually high level of Pb for the time period. Taken all together our skeletal microstructural results do not support the conclusion that Pb played a pivotal role in the loss of Franklin and his crew.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Traumatic diaphragmatic injury (TDI) is a rarely diagnosed injury in trauma. Previous studies have been limited in their evaluation of TDI because of small population size and ...center bias. Although injuries may be suspected based on penetrating mechanism, blunt injuries may be particularly difficult to detect. The American College of Surgeons National Trauma Data Bank is the largest trauma database in the United States. We hypothesized that we could identify specific injury patterns associated with blunt and penetrating TDIs. Methods We examined demographics, diagnoses, mechanism of injury, and outcomes for patients with TDI in 2012 as this is the largest and most recent dataset available. Comparisons were made using chi-square or independent samples t test. Results There were a total of 833,309 encounters in the National Trauma Data Bank in 2012. Three thousand eight hundred seventy-three patients had a TDI (.46%). Of those, 1,240 (33%) patients had a blunt mechanism and 2,543 (67%) had a penetrating mechanism. Patients with blunt TDI were older (44 ± 19 vs 31 ± 13 years, P < .001), had a higher injury severity score (33 ± 14 vs 24 ± 15, P < .001), and a higher mortality rate (19.8% vs 8.8%, P < .001). Compared with patients with penetrating injuries, those with blunt TDI were more likely to have injuries to the thoracic aorta (2.9% vs .5%, P < .001), lung (48.7% vs 28.1, P < .001), bladder (5.9% vs .7%, P < .001), and spleen (44.8% vs 29.1%, P < .001). Penetrating TDI was associated with liver and hollow viscus injuries. Conclusions Diaphragmatic injury is an uncommon but significant diagnosis in trauma patients. Blunt injuries may be more likely to be occult; however, a pattern of associated injuries to the aorta, lung, spleen, and bladder should prompt further workup for TDI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
Radionuclide imaging of phaeochromocytomas (PCCs) and paragangliomas (PGLs) involves various functional imaging techniques and approaches for accurate diagnosis, staging and tumour ...characterization. The purpose of the present guidelines is to assist nuclear medicine practitioners in performing, interpreting and reporting the results of the currently available SPECT and PET imaging approaches. These guidelines are intended to present information specifically adapted to European practice.
Methods
Guidelines from related fields, issued by the European Association of Nuclear Medicine and the Society of Nuclear Medicine, were taken into consideration and are partially integrated within this text. The same was applied to the relevant literature, and the final result was discussed with leading experts involved in the management of patients with PCC/PGL. The information provided should be viewed in the context of local conditions, laws and regulations.
Conclusion
Although several radionuclide imaging modalities are considered herein, considerable focus is given to PET imaging which offers high sensitivity targeted molecular imaging approaches.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Less than half of anthropogenic carbon dioxide emissions remain in the atmosphere. While carbon balance models imply large carbon uptake in tropical forests, direct on-the-ground observations are ...still lacking in Southeast Asia. Here, using long-term plot monitoring records of up to half a century, we find that intact forests in Borneo gained 0.43 Mg C ha
per year (95% CI 0.14-0.72, mean period 1988-2010) above-ground live biomass. These results closely match those from African and Amazonian plot networks, suggesting that the world's remaining intact tropical forests are now en masse out-of-equilibrium. Although both pan-tropical and long-term, the sink in remaining intact forests appears vulnerable to climate and land use changes. Across Borneo the 1997-1998 El Niño drought temporarily halted the carbon sink by increasing tree mortality, while fragmentation persistently offset the sink and turned many edge-affected forests into a carbon source to the atmosphere.
Conservation breeding programmes have become an increasingly important tool to save endangered species, yet despite the allocation of significant resources, efforts to create self-sustaining ...populations have met with limited success. The iconic giant panda (Ailuropoda melanoleuca) embodies the struggles associated with ex situ species conservation. Here we show that behavioural mate preferences in giant pandas predict reproductive outcomes. Giant pandas paired with preferred partners have significantly higher copulation and birth rates. Reproductive rates increase further when both partners show mutual preference for one another. If managers were to incorporate mate preferences more fully into breeding management, the production of giant panda offspring for China's reintroduction programme might be greatly expedited. When extended to the increasing numbers of species dependent on ex situ conservation breeding to avoid extinction, our findings highlight that mate preference and other aspects of informed behavioural management could make the difference between success and failure of these programmes.
We provide the first assessment of tropical peatland depth of burn (DoB) using structure from motion (SfM) photogrammetry, applied to imagery collected using a low-cost, low-altitude unmanned aerial ...vehicle (UAV) system operated over a 5.2 ha tropical peatland in Jambi Province on Sumatra, Indonesia. Tropical peat soils are the result of thousands of years of dead biomass accumulation, and when burned are globally significant net sources of carbon emissions. The El Nino year of 2015 saw huge areas of Indonesia affected by tropical peatland fires, more so than any year since 1997. However, the Depth of Burn (DoB) of these 2015 fires has not been assessed, and indeed has only previously been assessed in few tropical peatland burns in Kalimantan. Therefore, DoB remains arguably the largest uncertainty when undertaking fire emissions calculations in these tropical peatland environments. We apply a SfM photogrammetric methodology to map this DoB metric, and also investigate combustion heterogeneity using orthomosaic photography collected using the UAV system. We supplement this information with pre-burn airborne light detection and ranging (LiDAR) data, reducing uncertainty by estimating pre-burn soil height more accurately than from interpolation of adjacent unburned areas alone. Our pre-and post-fire Digital Terrain Models (DTMs) show accuracies of 0.04 and 0.05 m (root-mean-square error, RMSE) respectively, compared to ground-based global navigation satellite system (GNSS) surveys. Our final DoB map of a 5.2 ha degraded peat swamp forest area neighboring Berbak National Park (Sumatra, Indonesia) shows burn depths extending from close to zero to over 1 m, with a mean ( plus or minus 1 sigma ) DoB of 0.23 plus or minus 0.19 m. This lies well within the range found by the few other studies available (on Kalimantan; none are available on Sumatra). Our combustion heterogeneity analysis suggests the deepest burns, which extend to ~1.3 m, occur around tree roots. We use these DoB data within the Intergovernmental Panel on Climate Change (IPCC) default equation for fire emissions to estimate mean carbon emissions as 134 plus or minus 29 t times C times ha-1 for this peatland fire, which is in an area that had not had a recorded fire previously. This is amongst the highest per unit area fuel consumption anywhere in the world for landscape fires. Our approach provides significant uncertainty reductions in such emissions calculations via the reduction in DoB uncertainty, and by using the UAV SfM approach this is accomplished at a fraction of the cost of airborne LiDAR-albeit over limited sized areas at present. Deploying this approach at locations across Indonesia, sampling a variety of fire-affected landscapes, would provide new and important DoB statistics for producing optimized carbon and greenhouse gas (GHG) emissions estimates from peatland fires.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Quantifying the relationship between tree diameter and height is a key component of efforts to estimate biomass and carbon stocks in tropical forests. Although substantial site‐to‐site variation in ...height–diameter allometries has been documented, the time consuming nature of measuring all tree heights in an inventory plot means that most studies do not include height, or else use generic pan‐tropical or regional allometric equations to estimate height.
Using a pan‐tropical dataset of 73 plots where at least 150 trees had in‐field ground‐based height measurements, we examined how the number of trees sampled affects the performance of locally derived height–diameter allometries, and evaluated the performance of different methods for sampling trees for height measurement.
Using cross‐validation, we found that allometries constructed with just 20 locally measured values could often predict tree height with lower error than regional or climate‐based allometries (mean reduction in prediction error = 0.46 m). The predictive performance of locally derived allometries improved with sample size, but with diminishing returns in performance gains when more than 40 trees were sampled. Estimates of stand‐level biomass produced using local allometries to estimate tree height show no over‐ or under‐estimation bias when compared with biomass estimates using field measured heights. We evaluated five strategies to sample trees for height measurement, and found that sampling strategies that included measuring the heights of the ten largest diameter trees in a plot outperformed (in terms of resulting in local height–diameter models with low height prediction error) entirely random or diameter size‐class stratified approaches.
Our results indicate that even limited sampling of heights can be used to refine height–diameter allometries. We recommend aiming for a conservative threshold of sampling 50 trees per location for height measurement, and including the ten trees with the largest diameter in this sample.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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