Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impaired bioavailability and/or responsiveness to endogenous NO has been implicated in the ...pathogenesis of cardiovascular and other diseases. Current therapies that involve the use of organic nitrates and other NO donors have limitations, including non-specific interactions of NO with various biomolecules, lack of response and the development of tolerance following prolonged administration. Compounds that activate sGC in an NO-independent manner might therefore provide considerable therapeutic advantages. Here we review the discovery, biochemistry, pharmacology and clinical potential of haem-dependent sGC stimulators (including YC-1, BAY 41-2272, BAY 41-8543, CFM-1571 and A-350619) and haem-independent sGC activators (including BAY 58-2667 and HMR-1766).
Summary Background A third of the 2·5 billion people worldwide without access to improved sanitation live in India, as do two-thirds of the 1·1 billion practising open defecation and a quarter of the ...1·5 million who die annually from diarrhoeal diseases. We aimed to assess the effectiveness of a rural sanitation intervention, within the context of the Government of India's Total Sanitation Campaign, to prevent diarrhoea, soil-transmitted helminth infection, and child malnutrition. Methods We did a cluster-randomised controlled trial between May 20, 2010, and Dec 22, 2013, in 100 rural villages in Odisha, India. Households within villages were eligible if they had a child younger than 4 years or a pregnant woman. Villages were randomly assigned (1:1), with a computer-generated sequence, to undergo latrine promotion and construction or to receive no intervention (control). Randomisation was stratified by administrative block to ensure an equal number of intervention and control villages in each block. Masking of participants was not possible because of the nature of the intervention. However, households were not told explicitly that the purpose of enrolment was to study the effect of a trial intervention, and the surveillance team was different from the intervention team. The primary endpoint was 7-day prevalence of reported diarrhoea in children younger than 5 years. We did intention-to-treat and per-protocol analyses. This trial is registered with ClinicalTrials.gov , number NCT01214785. Findings We randomly assigned 50 villages to the intervention group and 50 villages to the control group. There were 4586 households (24 969 individuals) in intervention villages and 4894 households (25 982 individuals) in control villages. The intervention increased mean village-level latrine coverage from 9% of households to 63%, compared with an increase from 8% to 12% in control villages. Health surveillance data were obtained from 1437 households with children younger than 5 years in the intervention group (1919 children younger than 5 years), and from 1465 households (1916 children younger than 5 years) in the control group. 7-day prevalence of reported diarrhoea in children younger than 5 years was 8·8% in the intervention group and 9·1% in the control group (period prevalence ratio 0·97, 95% CI 0·83–1·12). 162 participants died in the intervention group (11 children younger than 5 years) and 151 died in the control group (13 children younger than 5 years). Interpretation Increased latrine coverage is generally believed to be effective for reducing exposure to faecal pathogens and preventing disease; however, our results show that this outcome cannot be assumed. As efforts to improve sanitation are being undertaken worldwide, approaches should not only meet international coverage targets, but should also be implemented in a way that achieves uptake, reduces exposure, and delivers genuine health gains. Funding Bill & Melinda Gates Foundation, International Initiative for Impact Evaluation (3ie), and Department for International Development-backed SHARE Research Consortium at the London School of Hygiene & Tropical Medicine.
Highly efficient red-emitting nitridosilicate phosphors Sr2Si5N8:Eu2+ and Ba1.5Sr0.5Si5N8:Eu2+ (doping level 1 %) applicable to phosphor converted pc-LEDs were synthesized in nanocrystalline form at ...low temperatures employing a novel single-source precursor approach. Synthesis starts from nanocrystalline silicon and uses mixed metal amides M(NH2)2 with M = Sr, Ba, Eu as reactive intermediates. In a second approach, a single-source precursor mixture obtained from a one-pot reaction of the corresponding elements (Sr/Ba, Eu, Si) was obtained in supercritical ammonia. Thermoanalytical in situ investigations gain a deeper insight into the degradation mechanism of the mixed metal amide precursors and revealed the onset for the formation of the 2-5-8 phosphor materials at temperatures slightly above 900 °C. Formation of the products is complete below 1400 °C. Under these conditions, the nitridosilicate phosphors form spherically shaped particles with crystallites of 200 nm in size. Spherical particles are desirable for phosphor application because light extraction may be improved by decreased light trapping and re-absorption losses. As a major advantage of the one-pot precursor approach, the exact Sr/Ba content in the solid solution series Sr2−x Ba x Si2N8:Eu2+ and the doping concentration of Eu2+ can easily be controlled in a wide range by the relative amount of the elemental starting materials (Sr, Ba, Eu, Si). Simultaneously, thorough mixing of these elements down to an atomic level (Sr, Ba, Eu) or at least at nanoscopic dimensions (silicon) is achieved by the solution approach. As a consequence, no milling and pre-reaction steps are necessary which might give rise to contamination. Advantageously, this approach can easily be extended to large-scale processes by simultaneously preserving complete mixing. Furthermore, the influence of the starting materials (single-source precursor, nanocrystalline silicon) and the reaction conditions on the crystal shape and finally on the luminescence properties of the products was investigated. The obtained nanophosphors exhibit luminescence properties comparable to coarsely crystalline nitridosilicate phosphor powders prepared by conventional high-temperature processing.
Using environmental, social, and governance (ESG) ratings from seven different data providers for a sample of firms in the S&P 500 Index between 2010 and 2017, we studied the relationship between ESG ...rating disagreement and stock returns. We found that stock returns are positively related to ESG rating disagreement, suggesting a risk premium for firms with higher ESG rating disagreement. The relationship is primarily driven by disagreement about the environmental dimension. We discuss the practical implications of our findings for firms' equity cost of capital as well as for investment managers and asset owners who use ESG investment strategies.
Narrow-band red-emitting luminescent CaBaLi2Al6N8:Eu2+ for potential application in illumination-grade white-light-emitting diodes (WLEDs) was synthesized by reaction of the metal hydrides and ...nitrides in molybdenum crucibles in a hot isostatic press. Upon irradiation with high-energy visible light (444 nm), the material exhibits intense red and infrared luminescence (emission maxima, 636–639 nm, 790 nm; full width at half-maximum (fwhm), 1095–1266 cm–1 (48–57 nm), ≈1450 cm–1 (89 nm)). The red emission from Eu occupying the Ba site is nearly optimal for use in WLEDs combining outstanding color rendition and excellent luminous efficacy and the most narrow-band Eu2+ emission observed to date. The infrared emission intensity from Eu occupying the Ca site can be limited by reducing the activator concentration (here, 0.02–5 atom % Eu). CaBaLi2Al6N8:Eu2+ crystallizes isotypically with RbNaLi6Si2O8 in the monoclinic space group C2/m (no. 12) with unit cell parameters a = 16.0851(2), b = 6.467 38(4), c = 8.042 42(13) Å, β = 90.004(2)°, and Z = 4. The material is obtained almost phase pure with <4 wt % AlN as side phase. The crystal structure consists of a network of vertex- and edge-sharing AlN4 and LiN4 tetrahedra with differently sized four-membered ring channels along 010 occupied by either cubelike coordinated Ca or Ba atoms or left empty.
Global challenges such as climate change or the refugee crises emphasize the necessity of altruism and cooperation. In a large-scale 9-month intervention study, we investigated the malleability of ...prosociality by three distinct mental trainings cultivating attention, socio-affective, or socio-cognitive skills. We assessed numerous established measures of prosociality that capture three core facets: Altruistically motivated behaviours, norm motivated behaviours, and self-reported prosociality. Results of multiple time point confirmatory factor analyses support the validity and temporal stability of this model. Furthermore, linear mixed effects models reveal differential effects of mental trainings on the subcomponents of prosociality: Only training care and compassion effectively boosted altruistically motivated behaviour. No effects were revealed for norm-based behaviour. Self-reported prosociality increased with all training modules; this increase was, however, unrelated to changes in task-based measures of altruistic behaviour. These findings corroborate our motivation-based framework of prosociality, challenge economic views of fixed preferences by showing that socio-affective training boosts altruism, and inform policy makers and society about how to increase global cooperation.
LEARNING, HYGIENE AND TRADITIONAL MEDICINE Bennett, Daniel; Naqvi, Asjad; Schmidt, Wolf-Peter
The Economic journal (London),
July 2018, Letnik:
128, Številka:
612
Journal Article
Recenzirano
Odprti dostop
Information provision is only an effective behaviour-change strategy if the information is credible. A novel programme augments conventional hygiene instruction by showing participants everyday ...microbes under a microscope. Through a randomised evaluation in Pakistan, we show that this programme leads to meaningful hygiene and health improvements, while instruction alone does not. Traditional medicine, which offers an alternative disease model, may undermine learning by strengthening prior beliefs about hygiene. We show that believers in traditional medicine have smaller impacts, suggesting that traditional and modern medical beliefs are substitutes and that traditional medicine may exacerbate the infectious disease burden in this context.
Oxonitridophosphates exhibit the potential for broad structural diversity, making them promising host‐compounds in phosphor‐converted light‐emitting diode applications. The novel ...monophyllo‐oxonitridophosphate β‐MgSrP3N5O2 was obtained by using the high‐pressure multianvil technique. The crystal structure was solved and refined based on single‐crystal X‐ray diffraction data and confirmed by powder X‐ray diffraction. β‐MgSrP3N5O2 crystallizes in the orthorhombic space group Cmme (no. 67, a=8.8109(6), b=12.8096(6), c=4.9065(3) Å, Z=4) and has a structure related to that of Ba2CuSi2O7. DFT calculations were performed to investigate the phase transition from α‐ to β‐MgSrP3N5O2 and to confirm the latter as the corresponding high‐pressure polymorph. Furthermore, the luminescence properties of Eu2+ doped samples of both polymorphs were investigated and discussed, showing blue and cyan emission, respectively (α‐MgSrP3N5O2; λmax=438 nm, fwhm=46 nm/2396 cm−1; β‐MgSrP3N5O2; λmax=502 nm, fwhm=42 nm/1670 cm−1).
With the discovery of β‐MgSrP3N5O2:Eu2+, an oxonitridophosphate with outstanding luminescence properties is presented. Structural comparison of the α‐phase already known from the literature with other classes of compounds allowed a possible basic structure to be predicted, which was confirmed experimentally. This approach could be applied to other (oxo)nitridophosphates known in the literature, leading to the discovery of additional host lattices for possible luminescent properties.
Rationale
Reproductive mood disorders, including premenstrual dysphoria (PMD) and postpartum depression (PPD), are characterized by affective dysregulation that occurs during specific reproductive ...states. The occurrence of illness onset during changes in reproductive endocrine function has generated interest in the role of gonadal steroids in the pathophysiology of reproductive mood disorders, yet the mechanisms by which the changing hormone milieu triggers depression in susceptible women remain poorly understood.
Objectives
This review focuses on one of the neurosteroid metabolites of progesterone — allopregnanolone (ALLO) — that acutely regulates neuronal function and may mediate affective dysregulation that occurs concomitant with changes in reproductive endocrine function. We describe the role of the “neuroactive” steroids estradiol and progesterone in reproductive endocrine-related mood disorders to highlight the potential mechanisms by which ALLO might contribute to their pathophysiology. Finally, using existing data, we test the hypothesis that changes in ALLO levels may trigger affective dysregulation in susceptible women.
Results
Although there is no reliable evidence that basal ALLO levels distinguish those with PMD or PPD from those without, existing animal models suggest potential mechanisms by which specific reproductive states may unmask susceptibility to affective dysregulation. Consistent with these models, initially euthymic women with PMD and those with a history of PPD show a negative association between depressive symptoms and circulating ALLO levels following progesterone administration.
Conclusions
Existing animal models and our own preliminary data suggest that ALLO may play an important role in the pathophysiology of reproductive mood disorders by triggering affective dysregulation in susceptible women.
PDF
