There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of ...established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials.
Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters.
The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6-17.9 years) and glycated hemoglobin 7.3% (6.6-8.4%) 56 mmol/mol (49-68 mmol/mol). Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval CI 32.7-36.8) and 31.8% (95% CI 29.7-33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively.
In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).
•Butanol production by bioconversion of renewable resource.•Clostridium acetobutylicum fermentation of unsupplemented cheese whey.•Operation of a biofilm packed bed reactor.•Optimization of operating ...conditions.
Butanol production by Clostridium acetobutylicum DSM 792 fermentation was investigated. Unsupplemented cheese whey was adopted as renewable feedstock. The conversion was successfully carried out in a biofilm packed bed reactor (PBR) for more than 3months.
The PBR was a 4cm ID, 16cm high glass tube with a 8cm bed of 3mm Tygon rings, as carriers. It was operated at the dilution rate between 0.4h−1 and 0.94h−1.
The cheese whey conversion process was characterized in terms of metabolites production (butanol included), lactose conversion and biofilm mass. Under optimized conditions, the performances were: butanol productivity 2.66g/Lh, butanol concentration 4.93g/L, butanol yield 0.26g/g, butanol selectivity of the overall solvents production 82wt%.
Better preparedness for summer heatwaves could mitigate their adverse effects on society. This can potentially be attained through an increased understanding of the relationship between heatwaves and ...one of their main dynamical drivers, atmospheric blocking. In the 1979-2015 period, we find that there is a significant correlation between summer heatwave magnitudes and the number of days influenced by atmospheric blocking in Northern Europe and Western Russia. Using three large global climate model ensembles, we find similar correlations, indicating that these three models are able to represent the relationship between extreme temperature and atmospheric blocking, despite having biases in their simulation of individual climate variables such as temperature or geopotential height. Our results emphasize the need to use large ensembles of different global climate models as single realizations do not always capture this relationship. The three large ensembles further suggest that the relationship between summer heatwaves and atmospheric blocking will not change in the future. This could be used to statistically model heatwaves with atmospheric blocking as a covariate and aid decision-makers in planning disaster risk reduction and adaptation to climate change.
High-risk triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage and onset of resistance to chemotherapy, thus representing an area in need ...of new therapeutic approaches. Programmed death-ligand 1 (PD-L1) expression is an adaptive mechanism of tumour resistance to tumour-infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, available data support the concept that blockade of PD-L1/programmed cell death protein 1 checkpoint may improve efficacy of classical chemotherapy.
Two hundred and eighty patients with TNBC were enrolled in this multicentre study (NCT002620280) and randomized to neoadjuvant carboplatin area under the curve 2 and nab-paclitaxel 125 mg/m2 intravenously (i.v.) on days 1 and 8, without (n = 142) or with (n = 138) atezolizumab 1200 mg i.v. on day 1. Both regimens were given q3 weeks for eight cycles before surgery followed by four cycles of an adjuvant anthracycline regimen. The primary aim of the study was to compare event-free survival (EFS), and an important secondary aim was the rate of pathological complete response (pCR defined as the absence of invasive cells in breast and lymph nodes). The primary population for all efficacy endpoints is the intention-to-treat (ITT) population.
The ITT analysis revealed that pCR rate after treatment with atezolizumab (48.6%) did not reach statistical significance compared to no atezolizumab 44.4%: odds ratio (OR) 1.18; 95% confidence interval 0.74-1.89; P = 0.48. Treatment-related adverse events were similar with either regimen except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab.
The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis, the presence of PD-L1 expression was the most significant factor influencing the rate of pCR (OR 2.08). Continuing follow-up for the EFS is ongoing, and molecular studies are under way.
•Atezolizumab with neoadjuvant carboplatin/nab-paclitaxel led to non-significantly higher pCR rate in PD-L1+ TNBC.•In other trials neoadjuvant ICIs and chemotherapy significantly improved pCR rate, but EFS was independent of pCR.•Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC.•Lack of pCR improvement may be misleading as to the impact of atezolizumab on long-term efficacy in high risk TNBC.
Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest ...carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.
The aim of the research was to study the effects of an insect meal from Hermetia illucens larvae (HILM) as complete replacement of soybean meal (SBM) on productive performance and blood profiles of ...laying hens, from 24 to 45 wk of age. A total of 108 24-week-old Lohmann Brown Classic laying hens was equally divided into 2 groups (54 hens/group, 9 replicates of 6 hens/group). From 24 to 45 wk of age, the groups were fed 2 different isoproteic and isoenergetic diets: the control group (SBM) was fed a corn-soybean meal based diet, while in the HILM group the soybean meal was completely replaced by Hermetia illucens larvae meal. Feed intake, number of eggs produced, and egg weight were recorded weekly along the trial. At 45 wk of age, blood samples were collected from 2 hens per replicate. The use of HIML led to a more favorable (P < 0.01) feed conversion ratio in hens but lay percentage, feed intake, average egg weight, and egg mass were higher (P < 0.01) in hens fed the SBM diet. Hens fed insect meal produced a higher percentage of eggs from small (S), medium (M), and extra-large (XL) classes (P < 0.01) than SBM, while the SBM group had a higher percentage of eggs from the large (L) class (P < 0.01). The levels of globulin and albumin to globulin ratio were, respectively, higher and lower (P < 0.05) in HILM than the SBM group. Cholesterol and triglycerides were higher (P < 0.05 and P < 0.01, respectively) in hens from SBM than in the HILM group. Blood levels of Ca were higher (P < 0.01) in hens fed insect meal, while creatinine was higher (P < 0.01) in blood of hens fed SBM. Hermetia illucens larvae meal can be a suitable alternative protein source for laying hens even if the complete replacement of soybean meal needs further investigation to avoid the negative effects on feed intake.
The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more ...aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage.
To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period.
Young adults (YAs: 18–29 years old) significantly differed from adults (30–59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011).
The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome.
NCT00510926, NCT00514488, NCT00769327, NCT00481052.
Cerebral palsy (CP) is a common, clinically heterogeneous group of disorders affecting movement and posture. Its prevalence has changed little in 50 years and the causes remain largely unknown. The ...genetic contribution to CP causation has been predicted to be ~2%. We performed whole-exome sequencing of 183 cases with CP including both parents (98 cases) or one parent (67 cases) and 18 singleton cases (no parental DNA). We identified and validated 61 de novo protein-altering variants in 43 out of 98 (44%) case-parent trios. Initial prioritization of variants for causality was by mutation type, whether they were known or predicted to be deleterious and whether they occurred in known disease genes whose clinical spectrum overlaps CP. Further, prioritization used two multidimensional frameworks-the Residual Variation Intolerance Score and the Combined Annotation-dependent Depletion score. Ten de novo mutations in three previously identified disease genes (TUBA1A (n=2), SCN8A (n=1) and KDM5C (n=1)) and in six novel candidate CP genes (AGAP1, JHDM1D, MAST1, NAA35, RFX2 and WIPI2) were predicted to be potentially pathogenic for CP. In addition, we identified four predicted pathogenic, hemizygous variants on chromosome X in two known disease genes, L1CAM and PAK3, and in two novel candidate CP genes, CD99L2 and TENM1. In total, 14% of CP cases, by strict criteria, had a potentially disease-causing gene variant. Half were in novel genes. The genetic heterogeneity highlights the complexity of the genetic contribution to CP. Function and pathway studies are required to establish the causative role of these putative pathogenic CP genes.
The objective of this study was to investigate the effects of medium composition on CO fermentation by Clostridium carboxidivorans. The focus was to reduce the medium cost preserving acceptable ...levels of solvent production.
Yeast extract (YE) concentration was set in the range of 0–3 g/L. Different reducing agents were investigated, including cysteine-HCl 0.6 g/L, pure cysteine 0.6 g/L, sodium sulphide (Na2S) 0.6 g/L, cysteine-sodium sulphide 0.6 g/L and cysteine-sodium sulphide 0.72 g/L. The concentration of the metal solution was decreased down to 25 % of the standard value. Fermentation tests were also carried out with and without tungsten or selenium.
The results demonstrated that under optimized conditions, namely yeast extract (YE) concentration set at 1 g/L, pure cysteine as the reducing agent and trace metal concentration reduced to 75 % of the standard value, reasonable solvent production was achieved in less than 150 h. Under these operating conditions, the production levels were found to be 1.39 g/L of ethanol and 0.27 g/L of butanol. Furthermore, the study revealed that selenium was not necessary for C. carboxidivorans fermentation, whereas the presence of tungsten played a crucial role in both cell growth and solvent production.
The optimization of the medium composition in CO fermentation by Clostridium carboxidivorans is crucial for cost-effective solvent production. Tuning the yeast extract (YE) concentration, using pure cysteine as the reducing agent and reducing trace metal concentration contribute to reasonable solvent production within a relatively short fermentation period. Tungsten is essential for cell growth and solvent production, while selenium is not required.
•The effect of yeast extract, reducing agents and trace metals was evaluated.•The synthetic medium was optimized in the concentration of each nutritional factor.•Selenium was not strictly necessary for C. carboxidivorans to ferment.•Tungsten presence was fundamental for cell growth and solvent production.
Leveraging renewable carbon-based resources for energy and chemical production is a promising approach to decrease reliance on fossil fuels. This entails a thermo/biotechnological procedure wherein ...bacteria, notably Clostridia, ferment syngas, converting CO or CO2 + H2 into Hexanol, Butanol and Ethanol (H-B-E fermentation). This work reports of Clostridium carboxidivorans performance in a stirred tank reactor continuously operated with respect to the gas and the cell/liquid phases. The primary objective was to assess acid and solvent production at pH 5.6 by feeding pure CO or synthetic syngas under gas flow differential conditions. Fermentation tests were conducted at four different dilution rates (DL) of the fresh medium in the range 0.034–0.25 h−1. The fermentation pathways of C. carboxidivorans were found to be nearly identical for both CO and syngas, with consistent growth and metabolite production at pH 5.6 within a range of dilution rates. Wash-out conditions were observed at a DL of 0.25 h−1 regardless of the carbon source. Ethanol was the predominant solvent produced, but a shift towards butanol production was observed with CO as the substrate and towards hexanol production with synthetic syngas. In particular, the maximum cell concentration (0.5 gDM/L) was obtained with pure CO at DL 0.05 h−1; the highest solvent productivity (60 mg/L*h of total solvent) was obtained at DL 0.17 h−1 by using synthetic syngas as C-source. The findings highlight the importance of substrate composition and operating conditions in syngas fermentation processes. These insights contribute to the optimization of syngas fermentation processes for biofuel and chemical production.
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•C. carboxidivorans was grown in a CSTR at pH= 5.6.•The effect of substrate gas and dilution rate was evaluated.•max cell concentration (0.5 gDM/L) was obtained with pure CO at DL 0.05 h−1.•max solvent productivity was 60 mg/L*h, at DL 0.17 h−1 using synthetic syngas.
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