Land use practices have had important implications for structuring household inequalities and broader political systems in the past. Our contribution examines settlement patterns in relation to ...political structure, household wealth, ecological productivity and agricultural techniques. Combining settlement pattern data with high–precision soils data, we examine the extent to which different trajectories of polity formation impact the settlement location and land use practices of intermediate elites and commoners. The Classic Maya (CE 250/300–900) polities of Baking Pot and Lower Dover in the Upper Belize River Valley serve as enlightening case studies because despite being situated near one another, the two centers emerged along very different trajectories. Whereas the polity of Baking Pot arose slowly, in tandem with surrounding demography, the neighboring polity of Lower Dover arose rapidly in the Late Classic period (CE 600–900) in an area which was already home to established local populations. Our analysis shows that while Baking Pot had substantial settlement clustering around its epicenter, populations at Lower Dover aggregated around secondary and tertiary centers farther away from the polity core. Analyses also demonstrate that most commoner and intermediate elite residences were situated on the most productive agricultural lands in the region, though some intermediate elite households were situated on hilltops or in border zones with marginal soil productivity for political and tactical reasons. Commoner households were situated on a range of productivity zones reflecting diverse land–use practices which had implications for household wealth. Our case study illustrates the importance of integrating land use practices into our reconstructions of ancient political hierarchies, especially in terms of understanding political strategies and household wealth.
Abstract
Aims
A polygenic risk score (PRS) has the potential to improve individual atherosclerotic cardiovascular disease (ASCVD) risk assessment. To determine whether a PRS combined with two ...clinical risk scores, the Systematic COronary Risk Evaluation 2 (SCORE2) and the Pooled Cohort Equation (PCE) improves the prediction of ASCVD.
Methods and results
Using a population-based European prospective cohort, with 6733 participants at the baseline (2003–2006), the PRS presenting the best predictive accuracy was combined with SCORE2 and PCE to assess their joint performances for predicting ASCVD Discrimination, calibration, Cox proportional hazard regression, and net reclassification index were assessed. : 4218 subjects (53% women; median age, 53.4 years), with 363 prevalent and incident ASCVD, were used to compare four PRSs. The metaGRS_CAD PRS presented the best predictive capacity (AUROC = 0.77) and was used in the following analyses. 3383 subjects (median follow-up of 14.4 years), with 190 first-incident ASCVD, were employed to test ASCVD risk prediction. The changes in C statistic between SCORE2 and PCE models and those combining metaGRS_CAD with SCORE2 and PCE were 0.008 (95% CI, −0.00008–0.02, P = 0.05) and 0.007 (95% CI, 0.005–0.01, P = 0.03), respectively. Reclassification was improved for people at clinically determined intermediate-risk for both clinical scores NRI of 9.6% (95% CI, 0.3–18.8) and 12.0% (95% CI, 1.5–22.6) for SCORE2 and PCE, respectively.
Conclusion
Combining a PRS with clinical risk scores significantly improved the reclassification of risk for incident ASCVD for subjects in the clinically determined intermediate-risk category. Introducing PRSs in clinical practice may refine cardiovascular prevention for subgroups of patients in whom prevention strategies are uncertain.
Lay Summary
The aim of this study is to determine whether using polygenic risk scores improves the prediction of atherosclerotic cardiovascular disease risk when combined with clinical scores currently recommended by European and US guidelines on cardiovascular prevention.
Graphical Abstract
Graphical Abstract
Polygenic risk scores, summing the weak to moderate contribution of >1mio of genetic variants derived from genome-wide association studies, are used to predict the genetic predisposition of developing ASCVD. Clinically determined intermediate-risk categories were defined according to each guideline (i.e. European Society of Cardiology for SCORE2 and American College of Cardiology/American Heart Association for PCE) and corresponded to the category where treatment should be considered but not recommended. In the figure on the left, the reclassification of people without ASCVD after integrating the PRS into equations is not shown. ASCVD; atherosclerotic cardiovascular disease; metaGRS_CAD; polygenic risk score from Inouye et al. (in Journal of the American College of Cardiology, 2018, doi: 10.1016/j.jacc.2018.07.079), PRS; polygenic risk score
A three‐dimensional (3‐D) inverse modeling scheme is used to constrain the direct surface emissions of carbon monoxide CO. A priori estimates of CO emissions are taken from various inventories and ...are included in the IMAGES model to compute the distribution of CO. The modeled CO mixing ratios are compared with observations at 39 CMDL stations, averaged over the years 1990–1996. The interannual variability of CO sources is therefore ignored. We show that the method used (time‐dependent synthesis inversion) is able to adjust the surface fluxes on a monthly basis in order to improve the agreement between the observed and the modeled CO mixing ratios at the stations. The Earth surface is divided into regions. The spatial distribution of CO sources is fixed inside each of these regions. The inversion scheme optimizes the intensities of the emissions fluxes for the following processes: technological activities, forest and savanna burning, agricultural waste burning and fuelwood use, soil/vegetation emissions, and oceanic emissions. The inversion significantly reduces the uncertainties on the surface sources over Europe, North America and Asia. The most striking result is the increase (almost by a factor of 2) of CO flux from Asia in all a posteriori scenarios. The uncertainties on the Southern Hemisphere emissions remain large after the inversion, because the current observational surface network is too sparse at these latitudes. The inversion, moreover, shifts the peak in biomass burning emissions in the Southern Hemisphere by one month. This temporal shift ensures a better match of the observed and modeled CO seasonal cycle at the Ascension Island station. We also attempted to optimize the annual and global productions of CO due to methane and NMHC. With the current set of data, the scheme was not able to differentiate between these two sources, and hence only the total chemical production of CO can be optimized.
The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently ...used treatment approaches.
This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.
Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.
These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
NCT02339441.
Natural killer (NK) cells are an important lymphocyte population in the nasal mucosa and play important roles in linking the innate and the adaptive immune response. Their two main functions are ...direct cell-mediated cytotoxicity and the release of cytokines. They are important during viral infections and cancer. Due to their location in the nasal mucosa, NK cells are likely exposed to inhaled pollutants, such as diesel exhaust. Whether and how exposure to diesel exhaust particles (DEP) affects NK cell function in the context of viral infections has not been investigated.
NK cells were isolated from peripheral blood obtained from normal healthy volunteers and subsequently stimulated with the viral mimetic polyinosinic:polycytidylic acid (pI:C), DEP, or pI:C+DEP for 18 hours. NK cells were subsequently analyzed for changes in surface marker expression, cytokine production, gene expression changes, and cytotoxic function using flow cytometry, ELISA, qRT-PCR, and cell-mediated cytotoxicity assay, respectively.
Stimulation of NK cells with pI:C and pI:C+DEP, but not DEP alone, increased the release of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70, IFN-γ and TNF-α. As compared to pI:C alone or pI:C+DEP, the release of IL-1β, IL-8 and TNF-α was significantly lower after DEP stimulation alone. Stimulation with pI:C alone increased the gene and protein expression of granzyme B and perforin, which was completely blunted by adding DEP. Addition of DEP further reduced CD16 expression in pI:C stimulated cells. Similarly, cell-mediated cytotoxicity was significantly reduced by the addition of DEP.
In the context of viral infection, DEP potentially reduces NK cells' ability to kill virus-infected host cells, in spite of normal cytokine levels, and this may increase susceptibility to viral infections . This reduction in the potential ability of NK cells to kill virus-infected host cells may increase the susceptibility to viral infections after DEP exposure.
Modulations of oscillatory electroencephalogram (EEG) activity in the induced gamma and theta frequency ranges (induced gamma and theta band responses; iGBRs: >30 Hz; iTBRs: ∼6 Hz) have been ...associated with retrieval of information from long-term memory. However, the specific functional role of these two forms of oscillatory activity remains unclear. The present study examines theta- and gamma-oscillations within a dual-process framework, which defines “familiarity” and “recollection” as the two component processes of recognition memory. During encoding, participants were instructed to make “bigger/smaller than a shoebox” or “living/nonliving” decisions for different object pictures. During retrieval “old/new” recognition was followed (for items judged old) by a source discrimination task regarding the decision made for each item at encoding. iGBRs (35–80 Hz; 210–330 msec) were higher for correctly identified “old” relative to “new” objects. Importantly, they did not distinguish between successful and unsuccessful source judgments. In contrast, iTBRs (4–7.5 Hz; 600–1200 msec) were sensitive to source discrimination. We propose that iGBRs mirror early associative processes linked to familiarity-related retrieval processes, whereas iTBRs reflect later onsetting, episodic, recollection-related mechanisms.
Abstract Aim of the study Identifying clinical, electrophysiological and biological predictors for 6-month neurological outcome in survivors at day 3 after cardiac arrest (CA) treated with ...therapeutic hypothermia (TH). Methods We conducted a retrospective cohort study of adults comatose after out-of hospital CA treated with TH. All data were collected from medical charts and laboratory files. Results Between January 2010 and March 2013, among the 130 analysed CA survivors, 27 (21%) had a good neurological outcome at 6 months and 103 (79%) had a poor neurological outcome, including 98 deaths. The Glasgow coma score motor response (GCS-M), pupillary reflexes and Neuron Specific Enolase (NSE) were the three best predictors of neurological outcome ( P < 0.0001). The area under the Receiver Operating Characteristic curve for NSE was 0.92 0.84–0.99. Conclusion NSE values, GCS-M scores and pupillary reflexes are the best predictors of poor 6-month outcome after out-of-hospital CA treated with TH. Of these, NSE values have the best-isolated prognostic performance when above 28.8 μg/L.
The morphological development, ultrastructural cytology, and molecular phylogeny of
Eurychasma dicksonii, a holocarpic oomycete endoparasite of phaeophyte algae, were investigated in laboratory ...cultures. Infection of the host algae by
E. dicksonii is initiated by an adhesorium-like infection apparatus. First non-walled, the parasite cell developed a cell wall and numerous large vacuoles once it had almost completely filled the infected host cell (foamy stage). Large-scale cytoplasmic changes led to the differentiation of a sporangium with peripheral primary cysts. Secondary zoospores appeared to be liberated from the primary cysts in the internal space left after the peripheral spores differentiated. These zoospores contained two phases of peripheral vesicles, most likely homologous to the dorsal encystment vesicles and K-bodies observed in other oomycetes. Following zoospore liberation the walls of the empty cyst were left behind, forming the so-called net sporangium, a distinctive morphological feature of this genus. The morphological and ultrastructural features of
Eurychasma were discussed in relation to similarities with other oomycetes. Both SSU rRNA and COII trees pointed to a basal position of
Eurychasma among the Oomycetes. The
cox2 sequences also revealed that the UGA codon encoded tryptophan, constituting the first report of stop codon reassignment in an oomycete mitochondrion.
Abstract Graves’ disease (GD) during pregnancy involves risks for the mother, foetus and neonate. Objective To compile an inventory of the clinical practices regarding the management of GD during ...pregnancy in the Poitou-Charentes region of France. This was a retrospective, multicentre study covering the period 2005 to 2012. Ninety-five pregnancies were reviewed: 14 GD diagnosed during pregnancy, 24 GD already treated with synthetic antithyroid drugs (SAT) prior to pregnancy, 25 GD in remission before pregnancy and 32 GD who had undergone thyroidectomy prior to pregnancy. In patients under SAT and/or with TSH receptor antibody levels (TRAb) > 3 N at the 2nd (T2) and/or 3rd trimester (T3) of pregnancy, a foetal thyroid ultrasound (FTU) was performed in 18/32 cases and neonatal thyroid screening (NTS) in 14/20 cases. One case of foetal hyperthyroidism, two of neonatal hyperthyroidism and three of foetal hypothyroidism (including one neonatal hypothyroidism) were observed. Propylthiouracil was the preferred treatment prescribed, whatever the trimester. A congenital malformation was observed in 4/19 foetuses exposed to carbimazole during the 1st trimester (T1). In operated patients, TSH levels were > 2.5 mIU/L during T1 in 23/32 cases, while TRAb were not assayed during pregnancy in 12/32 cases. The management of GD during pregnancy could be improved by adjusting SAT therapy during its course, titrating levothyroxine prior to conception and in early pregnancy in thyroidectomised patients, and a more targeted use of FTU during T2 and T3 and of neonatal thyroid screening.
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