Supporting the Specification and Runtime Validation of Asynchronous Calling Patterns in Reactive Systems

Wireless sensor networks (“sensornets”) are highly distributed and concurrent, with program actions bound to external stimuli. They exemplify a system class known as reactive systems, which comprise execution units that have “hidden” layers of control flow. A key obstacle in enabling reactive system developers to rigorously validate their implementations has been the absence of precise software component specifications and tools to assist in leveraging those specifications at runtime. We address this obstacle in three ways: (i) We describe a specification approach tailored for reactive environments and demonstrate its application in the context of sensornets. (ii) We describe the design and implementation of extensions to the popular nesC tool-chain that enable the expression of these specifications and automate the generation of runtime monitors that signal violations, if any. (iii) Finally, we apply the specification approach to a significant collection of the most commonly used software components in the TinyOS distribution and analyze the overhead involved in monitoring their correctness

Electroproduction of lightest nucleon resonances up to Q*2=12 GeV*2 in quark models at light front

The lightest nucleon resonances are described at light front as mixed states of the 3q cluster (“quark core”) possessing a definite value of the inner orbital momentum L = 0,1 and a hadron molecular state, N+σ or Λ+K. Helicity amplitudes of the resonance electroproduction off the proton are calculated at large Q2 up to 12 GeV2 and compared to the last CLAS data. At this basis we have estimated the probability of quark core in lightest nucleon resonances and predicted the high Q2 behaviour of the resonance electrocoupling

Toward a Multifaceted Heuristic of Digital Reading to Inform Assessment, Research, Practice, and Policy

In this commentary, the author explores the tension between almost 30 years of work that has embraced increasingly complex conceptions of digital reading and recent studies that risk oversimplifying digital reading as a singular entity analogous with reading text on a screen. The author begins by tracing a line of theoretical and empirical work that both informs and complicates our understanding of digital literacy and, more specifically, digital reading. Then, a heuristic is proposed to systematically organize, label, and define a multifaceted set of increasingly complex terms, concepts, and practices that characterize the spectrum of digital reading experiences. Research that informs this heuristic is used to illustrate how more precision in defining digital reading can promote greater clarity across research methods and advance a more systematic study of promising digital reading practices. Finally, the author discusses implications for assessment, research, practice, and policy

Network and Psychological Effects in Urban Movement

Correlations are regularly found in space syntax studies between graph-based configurational measures of street networks, represented as lines, and observed movement patterns. This suggests that topological and geometric complexity are critically involved in how people navigate urban grids. This has caused difficulties with orthodox urban modelling, since it has always been assumed that insofar as spatial factors play a role in navigation, it will be on the basis of metric distance. In spite of much experimental evidence from cognitive science that geometric and topological factors are involved in navigation, and that metric distance is unlikely to be the best criterion for navigational choices, the matter has not been convincingly resolved since no method has existed for extracting cognitive information from aggregate flows. Within the space syntax literature it has also remained unclear how far the correlations that are found with syntactic variables at the level of aggregate flows are due to cognitive factors operating at the level of individual movers, or they are simply mathematically probable network effects, that is emergent statistical effects from the structure of line networks, independent of the psychology of navigational choices. Here we suggest how both problems can be resolved, by showing three things: first, how cognitive inferences can be made from aggregate urban flow data and distinguished from network effects; second by showing that urban movement, both vehicular and pedestrian, are shaped far more by the geometrical and topological properties of the grid than by its metric properties; and third by demonstrating that the influence of these factors on movement is a cognitive, not network, effect

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Accurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. Methods: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. Findings: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. Interpretation: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. Funding: Bill & Melinda Gates Foundation

The configuration of Northern Hemisphere ice sheets through the Quaternary

Our understanding of how global climatic changes are translated into ice-sheet fluctuations and sea-level change is currently limited by a lack of knowledge of the configuration of ice sheets prior to the Last Glacial Maximum (LGM). Here, we compile a synthesis of empirical data and numerical modelling results related to pre-LGM ice sheets to produce new hypotheses regarding their extent in the Northern Hemisphere (NH) at 17 time-slices that span the Quaternary. Our reconstructions illustrate pronounced ice-sheet asymmetry within the last glacial cycle and significant variations in ice-marginal positions between older glacial cycles. We find support for a significant reduction in the extent of the Laurentide Ice Sheet (LIS) during MIS 3, implying that global sea levels may have been 30–40m higher than most previous estimates. Our ice-sheet reconstructions illustrate the current state-of-the-art knowledge of pre-LGM ice sheets and provide a conceptual framework to interpret NH landscape evolution

Induction of the trypanosome lymphocyte-triggering factor (TLTF) and neutralizing antibodies to the TLTF in experimental African trypanosomiasis

We have demonstrated that African trypanosomes secrete a novel trypanokine, the trypanosome-derived lymphocyte-triggering factor (TLTF), which activates CD8+ cells to produce interferon-γ (IFN-γ) that in turn stimulates parasite growth. The gene for TLTF was recently cloned, and recombinant TLTF (rTLTF) showed bioactivity that was similar to native TLTF. In this work, we employed two anti-TLTF monoclonal antibodies (mAbs) to detect levels of TLTF during Trypanosoma brucei brucei (T. b. brucei) infections in mice. Furthermore, rTLTF was utilized to assess levels of anti-TLTF antibodies. Mice with intact genes (wild type), and knockout mice with disrupted IFN-γ (IFN-γ−/−) or IFN-γR (IFN-γR−/−) genes were studied. The knockout mice were used in order to illustrate the role of IFN-γ in the production of antibodies to TLTF. While wild-type mice showed high parasitaemia accompanied by high TLTF levels and low anti-TLTF antibodies at day 3 postinfection (p.i.), low TLTF was measured together with increased anti-TLTF antibodies at day 21 p.i. IFN-γ−/− mice exhibited very low parasitaemia, TLTF and anti-TLTF antibody levels. In contrast, IFN-γR−/− mice revealed very high parasitaemia, increased TLTF levels, but decreased anti-TLTF antibodies. In a biological assay for TLTF, Fab′ fragments of anti-TLTF antibodies dose dependently inhibited the TLTF-induced IFN-γ production by splenocytes, suggesting a regulatory importance of these antibodies. Our data demonstrate a role of IFN-γ in the generation of neutralizing antibodies to TLTF. Furthermore, the induction of TLTF and its antibodies may constitute a new approach for future diagnosis of African trypanosomiasis