Diagnostic accuracy of positron emission tomography tracers for the differentiation of tumor progression from treatment-related changes in high-grade glioma:a systematic review and meta-analysis

Background: Post-treatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent response assessment in neuro-oncology (RANO) recommendations PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and meta-analysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: Pubmed, Web of Science and Embase were searched systematically. Study selection, data extraction and quality assessment were performed independently by two authors. Meta-analysis was performed using a bivariate random effects model when ≥ 5 studies were included. Results: 39 studies (11 tracers) were included in the systematic review. 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95%CI 72-92) and 84% (69-93), respectively. 18F-FET (7 studies, 172 lesions) demonstrated a sensitivity of 90% (81-95) and specificity of 85% (71-93). 11C-MET (8 studies, 151 lesions) sensitivity was 93% (80-98) and specificity was 82% (68-91). The number of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93-100% and 0-100% for 18F-FLT, 85-100% and 72-100% for 18F-FDOPA and 100% and 70-88% for 11C-CHO, respectively. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparable higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited, thus 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas

11C-methyl-L-methionine PET measuring parameters for the diagnosis of tumour progression against radiation-induced changes in brain metastases

OBJECTIVES: Radiation-induced changes (RIC) secondary to focal radiotherapy can imitate tumour progression in brain metastases and make follow-up clinical decision making unreliable. 11C-methyl-L-methionine-PET (MET-PET) is widely used for the diagnosis of RIC in brain metastases, but minimal literature exists regarding the optimum PET measuring parameter to be used. We analysed the diagnostic performance of different MET-PET measuring parameters in distinguishing between RIC and tumour progression in a retrospective cohort of brain metastasis patients. METHODS: 26 patients with 31 metastatic lesions were included on the basis of having undergone a PET scan due to radiological uncertainty of disease progression. The PET images were analysed and methionine uptake quantified using standardised-uptake-values (SUV) and tumour-to-normal tissue (T/N) ratios, generated as SUVmean, SUVmax, SUVpeak, T/Nmean, T/Nmax-mean and T/Npeak-mean. Metabolic-tumour-volume and total-lesion methionine metabolism were also computed. A definitive diagnosis of either RIC or tumour progression was established by clinicoradiological follow-up of least 4 months subsequent to the investigative PET scan. RESULTS: All MET-PET parameters except metabolic-tumour-volume showed statistically significant differences between tumour progression and lesions with RIC. Receiver-operating-characteristic curve and area-under the-curve analysis demonstrated the highest value of 0.834 for SUVmax with a corresponding optimum threshold of 3.29. This associated with sensitivity, specificity, positive predictive and negative predictive values of 78.57, 70.59%, 74.32 and 75.25% respectively. CONCLUSIONS: MET-PET is a useful modality for the diagnosis of RIC in brain metastases. SUVmax was the PET parameter with the greatest diagnostic performance. ADVANCES IN KNOWLEDGE: More robust comparisons between SUVmax and SUVpeak could enhance follow-up treatment planning

Sharing ICU Patient Data Responsibly Under the Society of Critical Care Medicine/European Society of Intensive Care Medicine Joint Data Science Collaboration: The Amsterdam University Medical Centers Database (AmsterdamUMCdb) Example.

OBJECTIVES: Critical care medicine is a natural environment for machine learning approaches to improve outcomes for critically ill patients as admissions to ICUs generate vast amounts of data. However, technical, legal, ethical, and privacy concerns have so far limited the critical care medicine community from making these data readily available. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have identified ICU patient data sharing as one of the priorities under their Joint Data Science Collaboration. To encourage ICUs worldwide to share their patient data responsibly, we now describe the development and release of Amsterdam University Medical Centers Database (AmsterdamUMCdb), the first freely available critical care database in full compliance with privacy laws from both the United States and Europe, as an example of the feasibility of sharing complex critical care data. SETTING: University hospital ICU. SUBJECTS: Data from ICU patients admitted between 2003 and 2016. INTERVENTIONS: We used a risk-based deidentification strategy to maintain data utility while preserving privacy. In addition, we implemented contractual and governance processes, and a communication strategy. Patient organizations, supporting hospitals, and experts on ethics and privacy audited these processes and the database. MEASUREMENTS AND MAIN RESULTS: AmsterdamUMCdb contains approximately 1 billion clinical data points from 23,106 admissions of 20,109 patients. The privacy audit concluded that reidentification is not reasonably likely, and AmsterdamUMCdb can therefore be considered as anonymous information, both in the context of the U.S. Health Insurance Portability and Accountability Act and the European General Data Protection Regulation. The ethics audit concluded that responsible data sharing imposes minimal burden, whereas the potential benefit is tremendous. CONCLUSIONS: Technical, legal, ethical, and privacy challenges related to responsible data sharing can be addressed using a multidisciplinary approach. A risk-based deidentification strategy, that complies with both U.S. and European privacy regulations, should be the preferred approach to releasing ICU patient data. This supports the shared Society of Critical Care Medicine and European Society of Intensive Care Medicine vision to improve critical care outcomes through scientific inquiry of vast and combined ICU datasets

Hookworm-Related Anaemia among Pregnant Women: A Systematic Review

Anaemia affects large numbers of pregnant women in developing countries and increases their risk of dying during pregnancy and delivering low birth weight babies, who in turn are at increased risk of dying. Human hookworm infection has long been recognized among the major causes of anaemia in poor communities, but understanding of the benefits of the management of hookworm infection in pregnancy has lagged behind the other major causes of maternal anaemia. Low coverage of anthelmintic treatment in maternal health programmes in many countries has been the result. After systematically reviewing the available literature we observed that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women. We also estimate that between a quarter and a third of pregnant women in sub-Saharan Africa are infected with hookworm and at risk of preventable hookworm-related anaemia. However, all identified intervention studies showed a benefit of deworming for maternal or child health and we argue that increased efforts should be made to increase the coverage of anthelmintic treatment among pregnant women

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Grasping the changes seen in older adults when reaching for objects of varied texture.

Old age is associated with reduced mobility of the hand. To investigate age related decline when reaching-to-lift an object we used sophisticated kinematic apparatus to record reaches carried out by healthy older and younger participants. Three objects of different widths were placed at three different distances, with objects having either a high or low friction surface (i.e. rough or slippery). Older participants showed quantitative differences to their younger counterparts - movements were slower and peak speed did not scale with object distance. There were also qualitative differences with older adults showing a greater propensity to stop the hand and adjust finger position before lifting objects. The older participants particularly struggled to lift wide slippery objects, apparently due to an inability to manipulate their grasp to provide the level of precision necessary to functionally enclose the object. These data shed light on the nature of age related changes in reaching-to-grasp movements and establish a powerful technique for exploring how different product designs will impact on prehensile behavior

The elusive archaeology of Kongo urbanism: the case of Kindoki, Mbanza Nsundi (Lower Congo, DRC)

We present here results, analyses and an in-depth historical contextualisation of the fieldwork undertaken in 2012 and 2013 at the Kindoki site in the Lower Congo (DRC). This site is linked with Mbanza Nsundi, one of the Kongo Kingdom's provincial capitals, which turns out to be archaeologically 'elusive'. Pinpointing its location proved to be particularly challenging. To this end, a historically-informed excavation methodology was developed that was never implemented in Central Africa before. We combined a strategy of systematic test pits with a large-scale 50 m grid approach. A cemetery was identified on Kindoki Hill with distinct but contemporaneous quarters of a 16th-17thcenturies settlement on both sides. The cemetery itself contains mainly 18th-century burials, in all likelihood of successive Nsundi rulers. The foreign, especially Portuguese, ceramics excavated on the hilltop and the hundreds of Venetian and likely Bavarian beads found in the graves are indicative of Mbanza Nsundi's connection to trade routes linking the Atlantic coast with the Pool region. The most striking discovery is that of a previously unknown type of comb-impressed pottery, from a pit with a calibrated radiocarbon date AD 1294-1393 (2 sigma). This suggests that a settlement had been developing at Kindoki since at least the 14th century, which allows us, for the very first time, to spatially bridge Kongo history and 'prehistory'. For the entire Lower Congo region only three 14C dates posterior to AD 1000 were available before the start of the KongoKing project, twelve have been added for just Kindoki

Degradation of p53 by Human Alphapapillomavirus E6 Proteins Shows a Stronger Correlation with Phylogeny than Oncogenicity

Human Papillomavirus (HPV) E6 induced p53 degradation is thought to be an essential activity by which high-risk human Alphapapillomaviruses (alpha-HPVs) contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types) to include members of all known HPV species groups within the Alphapapillomavirus genus.We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71) were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA) and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53.These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential