The value of rapid functional assays of germline p53 status in LFS and LFL families

We have tested two rapid assays of p53 function, namely the apoptotic assay and the FASAY as means of detecting germline p53 mutations in members of Li–Fraumeni and Li–Fraumeni-like families. Results of the functional assays have been compared with direct sequencing of all 11 exons of the p53 gene. The results show good agreement between the two functional assays and between them and sequencing. No false-positives or negatives were seen with either functional assay although the apoptotic assay gave one borderline result for an individual without a mutation. As an initial screen the apoptotic assay is not only rapid but inexpensive and very simple to perform. It would be expected to detect any germline defect that leads to loss of p53 function. The apoptotic assay could be ideal as a means of prescreening large numbers of samples and identifying those that require further investigation. The FASAY detects mutations in exons 4–10, is rapid and distinguishes between functionally important and silent mutations. © 2000 Cancer Research Campaig

Comparison of flipped learning and traditional lecture method for teaching digestive system diseases in undergraduate medicine: A prospective non-randomized controlled trial

Introduction: This study examined the effects of a large-scale flipped learning (FL) approach in an undergraduate course of Digestive System Diseases. Methods: This prospective non-randomized trial recruited 404 students over three academic years. In 2016, the course was taught entirely in a Traditional Lecture (TL) style, in 2017 half of the course (Medical topics) was replaced by FL while the remaining half (Surgical topics) was taught by TL and in 2018, the whole course was taught entirely by FL. Academic performance, class attendance and student’s satisfaction surveys were compared between cohorts. Results: Test scores were higher in the FL module (Medical) than in the TL module (Surgical) in the 2017 cohort but were not different when both components were taught entirely by TL (2016) or by FL (2018). Also, FL increased the probability of reaching superior grades (scores >7.0) and improved class attendance and students’ satisfaction. Conclusion: The holistic FL model is more effective for teaching undergraduate clinical gastroenterology compared to traditional teaching methods and has a positive impact on classroom attendances

The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

BACKGROUND: The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. METHODS: We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. RESULTS: Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. CONCLUSION: Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found

Analyses of an Expressed Sequence Tag Library from Taenia solium, Cysticerca

A method used to describe expressed genes at a specific stage in an organism is an EST library. In this method mRNA from a specific organism is isolated, transcribed into cDNA and sequenced. The sequence will derive from the 5′-end of the cDNA. The library will not have sequences from all genes, especially if they are expressed in low amounts or not at all in the studied stage. Also the library will mostly not contain full length sequences from genes, but expression patterns can be established. If EST libraries are made from different stages of the same organisms these libraries can be compared and differently expressed genes can be identified. Described here is an analysis of an EST library from the pig cysticerca which is thought to be similar to the stage giving the human neglected disease neurocysticercosis. Novel genes together with putative drug targets are examples of data presented

Fundamental Neutron Physics: a White Paper on Progress and Prospects in the US

Fundamental neutron physics, combining precision measurements and theory, probes particle physics at short range with reach well beyond the highest energies probed by the LHC. Significant US efforts are underway that will probe BSM CP violation with orders of magnitude more sensitivity, provide new data on the Cabibbo anomaly, more precisely measure the neutron lifetime and decay, and explore hadronic parity violation. World-leading results from the US Fundamental Neutron Physics community since the last Long Range Plan, include the world's most precise measurement of the neutron lifetime from UCN$\tau$, the final results on the beta-asymmetry from UCNA and new results on hadronic parity violation from the NPDGamma and n-${^3}$He runs at the FNPB (Fundamental Neutron Physics Beamline), precision measurement of the radiative neutron decay mode and n-${}^4$He at NIST. US leadership and discovery potential are ensured by the development of new high-impact experiments including BL3, Nab, LANL nEDM and nEDM@SNS. On the theory side, the last few years have seen results for the neutron EDM from the QCD $\theta$ term, a factor of two reduction in the uncertainty for inner radiative corrections in beta-decay which impacts CKM unitarity, and progress on {\it ab initio} calculations of nuclear structure for medium-mass and heavy nuclei which can eventually improve the connection between nuclear and nucleon EDMs. In order to maintain this exciting program and capitalize on past investments while also pursuing new ideas and building US leadership in new areas, the Fundamental Neutron Physics community has identified a number of priorities and opportunities for our sub-field covering the time-frame of the last Long Range Plan (LRP) under development. This white paper elaborates on these priorities.Comment: arXiv admin note: text overlap with arXiv:2304.0345

The Multiplanet System TOI-421*: A Warm Neptune and a Super Puffy Mini-Neptune Transiting a G9 V Star in a Visual Binary*

We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations—comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echellé Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution Échelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements—and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of Pb = 5.19672 ± 0.00049 days, a mass of Mb = 7.17 ± 0.66 M⊕, and a radius of Rb = ${2.68}_{-0.18}^{+0.19}$ R⊕, whereas the outer warm Neptune, TOI-421 c, has a period of Pc = 16.06819 ± 0.00035 days, a mass of Mc = ${16.42}_{-1.04}^{+1.06}$ M⊕, a radius of Rc = ${5.09}_{-0.15}^{+0.16}$ R⊕, and a density of ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3. With its characteristics, the outer planet (ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Lyα transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed

Challenging local realism with human choices

A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism 1, in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings 2,3 . Although technology can satisfy the first two of these requirements 4-7, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests 8 . Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology 9 . The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons 5,6, single atoms 7, atomic ensembles 10 and superconducting devices 11 . Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties 13 ), the utilization of video-game methods 14 for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science

Carbon uptake by mature Amazon forests has mitigated Amazon nations' carbon emissions

Background: Several independent lines of evidence suggest that Amazon forests have provided a significant carbon sink service, and also that the Amazon carbon sink in intact, mature forests may now be threatened as a result of different processes. There has however been no work done to quantify non-land-use-change forest carbon fluxes on a national basis within Amazonia, or to place these national fluxes and their possible changes in the context of the major anthropogenic carbon fluxes in the region. Here we present a first attempt to interpret results from groundbased monitoring of mature forest carbon fluxes in a biogeographically, politically, and temporally differentiated way. Specifically, using results from a large long-term network of forest plots, we estimate the Amazon biomass carbon balance over the last three decades for the different regions and nine nations of Amazonia, and evaluate the magnitude and trajectory of these differentiated balances in relation to major national anthropogenic carbon emissions. Results: The sink of carbon into mature forests has been remarkably geographically ubiquitous across Amazonia, being substantial and persistent in each of the five biogeographic regions within Amazonia. Between 1980 and 2010, it has more than mitigated the fossil fuel emissions of every single national economy, except that of Venezuela. For most nations (Bolivia, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname) the sink has probably additionally mitigated all anthropogenic carbon emissions due to Amazon deforestation and other land use change. While the sink has weakened in some regions since 2000, our analysis suggests that Amazon nations which are able to conserve large areas of natural and semi-natural landscape still contribute globally-significant carbon sequestration. Conclusions: Mature forests across all of Amazonia have contributed significantly to mitigating climate change for decades. Yet Amazon nations have not directly benefited from providing this global scale ecosystem service. We suggest that better monitoring and reporting of the carbon fluxes within mature forests, and understanding the drivers of changes in their balance, must become national, as well as international, priorities

Carbon uptake by mature Amazon forests has mitigated Amazon nations' carbon emissions

BACKGROUND: Several independent lines of evidence suggest that Amazon forests have provided a significant carbon sink service, and also that the Amazon carbon sink in intact, mature forests may now be threatened as a result of different processes. There has however been no work done to quantify non-land-use-change forest carbon fluxes on a national basis within Amazonia, or to place these national fluxes and their possible changes in the context of the major anthropogenic carbon fluxes in the region. Here we present a first attempt to interpret results from ground-based monitoring of mature forest carbon fluxes in a biogeographically, politically, and temporally differentiated way. Specifically, using results from a large long-term network of forest plots, we estimate the Amazon biomass carbon balance over the last three decades for the different regions and nine nations of Amazonia, and evaluate the magnitude and trajectory of these differentiated balances in relation to major national anthropogenic carbon emissions. RESULTS: The sink of carbon into mature forests has been remarkably geographically ubiquitous across Amazonia, being substantial and persistent in each of the five biogeographic regions within Amazonia. Between 1980 and 2010, it has more than mitigated the fossil fuel emissions of every single national economy, except that of Venezuela. For most nations (Bolivia, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname) the sink has probably additionally mitigated all anthropogenic carbon emissions due to Amazon deforestation and other land use change. While the sink has weakened in some regions since 2000, our analysis suggests that Amazon nations which are able to conserve large areas of natural and semi-natural landscape still contribute globally-significant carbon sequestration. CONCLUSIONS: Mature forests across all of Amazonia have contributed significantly to mitigating climate change for decades. Yet Amazon nations have not directly benefited from providing this global scale ecosystem service. We suggest that better monitoring and reporting of the carbon fluxes within mature forests, and understanding the drivers of changes in their balance, must become national, as well as international, priorities