Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to ...contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities.
The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning <R1,000 per month), and high prevalence of maternal psychosocial risk factors including alcohol use in pregnancy (n = 95; 14.5%), smoking (n = 241; 34.7%), depression (n = 156; 23.7%), lifetime intimate partner violence (n = 310; 47.3%), and history of maternal childhood trauma (n = 228; 34.7%). A high proportion of children were categorised as delayed (defined by scoring < -1 standard deviation below the mean scaled score calculated using the BSID-III norms from a United States population) in different domains (369 50.5% cognition, 402 55.6% receptive language, 389 55.4% expressive language, 169 23.2% fine motor, and 267 38.4% gross motor). Four hundred five (55.3%) children had >1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition β = -0.74; 95% CI -1.46 to -0.03, p = 0.042, receptive language β = -1.10; 95% CI -1.70 to -0.49, p < 0.001, expressive language β = -1.65; 95% CI -2.46 to -0.84, p < 0.001, and fine motor β = -0.70; 95% CI -1.20 to -0.20, p = 0.006 scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitations of the study include attrition of sample from birth to assessment age and missing data in some exposure areas from those assessed.
This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group.
The Tumor-Node-Metastasis (TNM) classification on cancer staging, jointly developed by the American Joint Commission on Cancer (AJCC) and the Union for International Cancer Control (UICC), has been ...updated to its 8th edition with two contemporaneous versions published by the AJCC and UICC. While the goal of the AJCC and UICC is to have identical TNM staging systems, differences exist between these two publications including in the staging of urologic cancers. Among several new facets in the AJCC staging manual, a select few of greater import include an expanded section on imaging, presentation of levels of evidence for significant changes, and endorsement of risk assessment models that pass the AJCC quality criteria such as in prostate cancer. The updates for urologic cancers in the AJCC stage categories can be grouped into: (1) newly defined TNM categories and prognostic stage groupings, (2) clarifications and refinements of previously defined categories, and (3) more systematic and expanded presentation of prognostic factors. Changes are harmonized with the current reporting and treatment guidelines. Contributions from genitourinary pathology are evident in the AJCC classification from many of the International Society of Urological Pathology (ISUP) consensus conferences on prostate, kidney, testicular, and penile neoplasms that addressed staging issues and the timely publication of the 4th edition of the World Health Organization (WHO) classification of urinary and male genital organ tumors. New grading approaches for penile (WHO/ISUP grade), prostate (Grade group), and kidney (WHO/ISUP nucleolar grade) cancers were adopted in the AJCC system. Many of these updates in the AJCC staging manual are also included in the 8th UICC TNM edition. In an effort to achieve the optimal staging recommendations for urologic cancers, updates in the 8th TNM edition were generated through the acquisition of best evidences, tapping interdisciplinary resources including consensus recommendations, and enhanced data analysis.
In this report, we explain the seminal changes in the 8th edition of the Tumor-Node-Metastasis staging system for urologic cancers. Major stage category definitional changes are in Tumor-Node-Metastasis classifications of testicular, penile, and prostate cancer which improve patient stratification for prognosis and management.
Refining the standards that provide the best possible staging system is a never-ending process. The 8th edition continues in that tradition with a more focused attempt to incorporate nonanatomic factors into staging. This approach is most evident in staging of prostate cancers where nonanatomic factors including grade of tumor and serum prostate specific antigen levels significantly impact American Joint Committee on Cancer prognostic stage group assignment whereby which even some organ-confined cancers may be classified as stage III cancer.
Polymers are used in simple consumer items like carpets, furniture, glues, and clothing but are also used in advanced engineering, including materials used in the aerospace industry. Therefore, ...polymers and consequently their monomers play an important role in our everyday life. Currently, most of the monomers are produced from fossil resources, the supply of which is diminishing. In this paper we review strategies and catalytic processes to obtain currently used and potentially new monomers from renewable bio-based feedstocks and platform chemicals. This Review is divided by type of monomer and includes diacids and esters, diols, hydroxy acids and esters, lactones, carbonates, cyclic ethers, diamines, amino acids and lactams, alkenes, acrylics, and conjugated dienes. Only routes based on the use of homogeneous catalysis, heterogeneous catalysis, or bio-catalysis are described. Fermentative processes are not discussed.
We show that the numerical renormalization group is a viable multi-band impurity solver for dynamical mean-field theory (DMFT), offering unprecedented real-frequency spectral resolution at ...arbitrarily low energies and temperatures. We use it to obtain a numerically exact DMFT solution to the Hund metal problem for a three-band model on a Bethe lattice at 1/3 filling. The ground state is a Fermi liquid. The one-particle spectral function undergoes a coherence-incoherence crossover with increasing temperature, with spectral weight being transferred from low to high energies. Further, it exhibits a strong particle-hole asymmetry. In the incoherent regime, the self-energy displays approximate power-law behavior for positive frequencies only. The spin and orbital spectral functions show "spin-orbital separation": spin screening occurs at much lower energies than orbital screening. The renormalization group flows clearly reveal the relevant physics at all energy scales.
•We model strategic investment decisions for distributed energy resources and passive measures.•Compare the demonstrated mixed integer optimization model with other existing tools.•Describe the ...mathematical formulation of the tool.•Demonstrate the capabilities at an Austrian University building.•Show the trade-off between cost and CO2 reduction and report on the optimal investment decisions.
The pressuring need to reduce the import of fossil fuels as well as the need to dramatically reduce CO2 emissions in Europe motivated the European Commission (EC) to implement several regulations directed to building owners. Most of these regulations focus on increasing the number of energy efficient buildings, both new and retrofitted, since retrofits play an important role in energy efficiency. Overall, this initiative results from the realization that buildings will have a significant impact in fulfilling the 20/20/20-goals of reducing the greenhouse gas emissions by 20%, increasing energy efficiency by 20%, and increasing the share of renewables to 20%, all by 2020.
The Distributed Energy Resources Customer Adoption Model (DER-CAM) is an optimization tool used to support DER investment decisions, typically by minimizing total annual costs or CO2 emissions while providing energy services to a given building or microgrid site. This paper shows enhancements made to DER-CAM to consider building retrofit measures along with DER investment options. Specifically, building shell improvement options have been added to DER-CAM as alternative or complementary options to investments in other DER such as PV, solar thermal, combined heat and power, or energy storage. The extension of the mathematical formulation required by the new features introduced in DER-CAM is presented and the resulting model is demonstrated at an Austrian Campus building by comparing DER-CAM results with and without building shell improvement options. Strategic investment results are presented and compared to the observed investment decision at the test site. Results obtained considering building shell improvement options suggest an optimal weighted average U value of about 0.53W/(m2K) for the test site. This result is approximately 25% higher than what is currently observed in the building, suggesting that the retrofits made in 2002 were not optimal. Furthermore, the results obtained with DER-CAM illustrate the complexity of interactions between DER and passive measure options, showcasing the need for a holistic optimization approach to effectively optimize energy costs and CO2 emissions. The simultaneous optimization of building shell improvements and DER investments enables building owners to take one step further towards nearly zero energy buildings (nZEB) or nearly zero carbon emission buildings (nZCEB), and therefore support the 20/20/20 goals.
The stringent regulation of cell cycle progression helps to maintain genetic stability in cells. MicroRNAs (miRNAs) are critical regulators of gene expression in diverse cellular pathways, including ...developmental patterning, hematopoietic differentiation and antiviral defense. Here, we show that two c-Myc-regulated miRNAs, miR-17 and miR-20a, govern the transition through G1 in normal diploid human cells. Inhibition of these miRNAs leads to a G1 checkpoint due to an accumulation of DNA double-strand breaks, resulting from premature temporal accumulation of the E2F1 transcription factor. Surprisingly, gross changes in E2F1 levels were not required to initiate the DNA damage response and checkpoint, as these responses could occur with a less than twofold change in E2F1 protein levels. Instead, our findings indicate that the precise timing of E2F1 expression dictates S-phase entry and that accurate timing of E2F1 accumulation requires converging signals from the Rb/E2F pathway and the c-Myc-regulated miR-17 and miR-20a miRNAs to circumvent a G1 checkpoint arising from the untimely accumulation of E2F1. These data provide a mechanistic view of miRNA-based regulation of E2F1 in the context of the emerging model that miRNAs coordinate the timing of cell cycle progression.
Physical properties of multi-orbital materials depend not only on the strength of the effective interactions among the valence electrons but also on their type. Strong correlations are caused by ...either Mott physics that captures the Coulomb repulsion among charges, or Hund physics that aligns the spins in different orbitals. We identify four energy scales marking the onset and the completion of screening in orbital and spin channels. The differences in these scales, which are manifest in the temperature dependence of the local spectrum and of the charge, spin and orbital susceptibilities, provide clear signatures distinguishing Mott and Hund physics. We illustrate these concepts with realistic studies of two archetypal strongly correlated materials, and corroborate the generality of our conclusions with a model Hamiltonian study.
Endophytic fungi have been demonstrated to produce bioactive secondary metabolites, some of which promote plant growth. Three endophytic fungi isolated from healthy plants living in dehesas of ...Extremadura (Spain) were identified and evaluated for their ability to produce phytohormone-like substances, antioxidant activity, total polyphenol content, phosphate solubilization ability and siderophore and ammonia production. The filtrates and extracts produced by the three endophytes were applied to Lolium multiflorum seeds and seedlings under both in vitro and greenhouse conditions, to analyse their influence on plant growth traits such as germination, vigour index, chlorophyll data, number and length of leaves and roots, and dry weight. All three endophytes, which were identified as Fusarium avenaceum, Sarocladium terricola and Xylariaceae sp., increased the germination of L. multiflorum seeds by more than 70%. Shoot and root length, plant dry weight and the number of roots were positively affected by the application of fungal filtrates and/or extracts, compared with controls. The tentative HPLC-MS identification of phytohormone-like substances, such as gibberellin A2 and zeatin, or the antioxidant acetyl eugenol, may partially explain the mechanisms of L. multiflorum plant growth promotion after the application of fungal filtrates and/or extracts.
Summary Background Non-clear cell renal cell carcinomas are histologically and genetically diverse kidney cancers with variable prognoses, and their optimum initial treatment is unknown. We aimed to ...compare the mTOR inhibitor everolimus and the VEGF receptor inhibitor sunitinib in patients with non-clear cell renal cell carcinoma. Methods We enrolled patients with metastatic papillary, chromophobe, or unclassified non-clear cell renal cell carcinoma with no history of previous systemic treatment. Patients were randomly assigned (1:1) to receive everolimus (10 mg/day) or sunitinib (50 mg/day; 6-week cycles of 4 weeks with treatment followed by 2 weeks without treatment) administered orally until disease progression or unacceptable toxicity. Randomisation was stratified by Memorial Sloan Kettering Cancer Center risk group and papillary histology. The primary endpoint was progression-free survival in the intention-to-treat population using the RECIST 1.1 criteria. Safety was assessed in all patients who were randomly assigned to treatment. This study is registered with ClinicalTrials.gov , number NCT01108445. Findings Between Sept 23, 2010, and Oct 28, 2013, 108 patients were randomly assigned to receive either sunitinib (n=51) or everolimus (n=57). As of December, 2014, 87 progression-free survival events had occurred with two remaining active patients, and the trial was closed for the primary analysis. Sunitinib significantly increased progression-free survival compared with everolimus (8·3 months 80% CI 5·8–11·4 vs 5·6 months 5·5–6·0; hazard ratio 1·41 80% CI 1·03–1·92; p=0·16), although heterogeneity of the treatment effect was noted on the basis of histological subtypes and prognostic risk groups. No unexpected toxic effects were reported, and the most common grade 3–4 adverse events were hypertension (12 24% of 51 patients in the sunitinib group vs one 2% of 57 patients in the everolimus group), infection (six 12% vs four 7%), diarrhoea (five 10% vs one 2%), pneumonitis (none vs five 9%), stomatitis (none vs five 9%), and hand-foot syndrome (four 8% vs none). Interpretation In patients with metastatic non-clear cell renal cell carcinoma, sunitinib improved progression-free survival compared with everolimus. Future trials of novel agents should account for heterogeneity in disease outcomes based on genetic, histological, and prognostic factors. Funding Novartis and Pfizer.
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