Learning from changes concurrent with implementing a complex and dynamic intervention to improve urban maternal and perinatal health in Dar es Salaam, Tanzania, 2011-2019

Introduction Rapid urbanisation in Dar es Salaam, the main commercial hub in Tanzania, has resulted in congested health facilities, poor quality care, and unacceptably high facility-based maternal and perinatal mortality. Using a participatory approach, the Dar es Salaam regional government in partnership with a non-governmental organisation, Comprehensive Community Based Rehabilitation in Tanzania, implemented a complex, dynamic intervention to improve the quality of care and survival during pregnancy and childbirth. The intervention was rolled out in 22 public health facilities, accounting for 60% of the city's facility births. Methods Multiple intervention components addressed gaps across the maternal and perinatal continuum of care (training, infrastructure, routine data quality strengthening and utilisation). Quality of care was measured with the Standards-Based Management and Recognition tool. Temporal trends from 2011 to 2019 in routinely collected, high-quality data on facility utilisation and facility-based maternal and perinatal mortality were analysed. Results Significant improvements were observed in the 22 health facilities: 41% decongestion in the three most overcrowded hospitals and comparable increase in use of lower level facilities, sixfold increase in quality of care, and overall reductions in facility-based maternal mortality ratio (47%) and stillbirth rate (19%). Conclusions This collaborative, multipartner, multilevel real-world implementation, led by the local government, leveraged structures in place to strengthen the urban health system and was sustained through a decade. As depicted in the theory of change, it is highly plausible that this complex intervention with the mediators and confounders contributed to improved distribution of workload, quality of maternity care and survival at birth.Research into fetal development and medicin

A simple dummy liver assist device prolongs anhepatic survival in a porcine model of total hepatectomy by slight hypothermia

<p>Abstract</p> <p>Background</p> <p>Advances in intensive care support such as therapeutic hypothermia or new liver assist devices have been the mainstay of treatment attempting to bridge the gap from acute liver failure to liver transplantation, but the efficacy of the available devices in reducing mortality has been questioned. To address this issue, the present animal study was aimed to analyze the pure clinical effects of a simple extracorporeal dummy device in an anhepatic porcine model of acute liver failure.</p> <p>Methods</p> <p>Total hepatectomy was performed in ten female pigs followed by standardized intensive care support until death. Five animals (dummy group, n = 5) underwent additional cyclic connection to an extracorporeal dummy device which consisted of a plasma separation unit. The separated undetoxified plasma was completely returned to the pigs circulation without any plasma substitution or exchange in contrast to animals receiving intensive care support alone (control group, n = 5). All physiological parameters such as vital and ventilation parameters were monitored electronically; laboratory values and endotoxin levels were measured every 8 hours.</p> <p>Results</p> <p>Survival of the dummy device group was 74 ± 6 hours in contrast to 53 ± 5 hours of the control group which was statistically significant (p < 0.05). Body temperature 24 hours after hepatectomy was significantly lower (36.5 ± 0.5°C vs. 38.2 ± 0.7°C) in the dummy device group. Significant lower values were measured for blood lactate (1.9 ± 0.2 vs. 2.5 ± 0.5 mM/L) from 16 hours, creatinine (1.5 ± 0.2 vs. 2.0 ± 0.3 mg/dL) from 40 hours and ammonia (273 ± 122 vs. 1345 ± 700 μg/dL) from 48 hours after hepatectomy until death. A significant rise of endotoxin levels indicated the onset of sepsis at time of death in 60% (3/5) of the dummy device group animals surviving beyond 60 hours from hepatectomy.</p> <p>Conclusions</p> <p>Episodes of slight hypothermia induced by cyclic connection to the extracorporeal dummy device produced a significant survival benefit of more than 20 hours through organ protection and hemodynamic stabilisation. Animal studies which focus on a survival benefit generated by liver assist devices should especially address the aspect of slight transient hypothermia by extracorporeal cooling.</p

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.Objectives: This project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk of CV-related traits. Methods: 1946 GCA patients with clinicodemographic data at GCA presentation were included. Associations between pre-existing CV-related traits (including Polygenic Risk Scores (PRS) for CV traits) and cranial ischaemic complications were tested. A model for cranial ischaemic complications was optimised using an elastic net approach. Positional gene mapping of associated PRS was performed to improve biological understanding. Results: In a sample of 1946 GCA patients (median age=71, 68.7% female), 17% had cranial ischaemic complications at presentation. In univariable analyses, 10 variables were associated with complications (likelihood-ratio test p≤0.05). In multivariable analysis, the two variables with the strongest effects, with or without PRS in the model, were anticoagulant therapy (adjusted OR (95% CI)=0.21 (0.05 to 0.62), p=4.95 710-3) and age (adjusted OR (95% CI)=1.60 (0.73 to 3.66), p=2.52 710-3, for ≥80 years versus &lt;60 years). In sensitivity analyses omitting anticoagulant therapy from multivariable analysis, age and hypertension were associated with cranial ischaemic complications at presentation (hypertension: adjusted OR (95% CI)=1.35 (1.03 to 1.75), p=0.03). Positional gene mapping of an associated transient ischaemic attack PRS identified TEK, CD96 and MROH9 loci. Conclusion: Age and hypertension were risk factors for cranial ischaemic complications at GCA presentation, but in this dataset, anticoagulation appeared protective. Positional gene mapping suggested a role for immune and coagulation-related pathways in the pathogenesis of complications. Further studies are needed before implementation in clinical practice

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study

Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. Methods: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. Findings: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10–8; OR 1·19 [95% CI 1·12–1·26]) and VTN (rs704; p=2·75 × 10–9; OR 0·84 [0·79–0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10–8; OR 1·18 [1·12–1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15–3·82]; p=1·73 × 10–13). Interpretation: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. Funding: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Researc

TRANSLATIONAL BASIS SET CONTRACTION IN VARIATIONAL REACTIVE SCATTERING

A new translational basis set is introduced for quantum reactive scattering calculations that use the log derivative version of the Kohn variational principle. This basis set, which is similar in many respects to that used in electron-atom scattering calculations by Burke and Robb, is obtained by contracting a primitive basis of Lobatto shape functions to the box eigenfunctions of a one-dimensional reference Hamiltonian H0. In addition, a single energy-dependent scattering function is included in the variational expansion to ensure completeness at the boundary of the box. One fairly obvious choice for the reference Hamiltonian in an atom-diatom reaction is suggested, and all of the equations which are actually needed to implement the method in this context are carefully described. Example applications to the three-dimensional F + H2 reaction are then chosen to illustrate the practical potential of the approach. © 1990 American Institute of Physics

Expression and content of terminal oxidases in Azotobacter vinelandii grown with excess NH4+ are modulated by O-2 supply

The influence of the rate of O2 supply to batch cultures on the contents of cytochromes bd and 'o' in NH4 +-grown Azotobacter vinelandii has been investigated. Difference spectra at room temperature (reduced + CO minus reduced) were recorded for whole cells of a wild-type strain and mutants which either lacked or over-produced the cytochrome bd-type terminal oxidase encoded by cydAB. A Tn5-B20 insertion in cydB in the former mutant also provided a means of monitoring cydAB gene expression from measurements of β-galactosidase activity. The content of cytochrome d in the wild-type, and the expression of cydAB-lacZ, in the mutant, increased as the O2 supply was raised, suggesting that O2 regulates cydAB expression even in the absence of diazotrophy. In a strain carrying a mutation in cydR, a regulatory gene upstream of cydAB, and which over-produces cytochrome bd, the responses to O2 supply during growth at different O2 supply rates were reversed. Changes in the content of a haemoprotein detectable in low temperature photodissociation spectra, and attributed to cytochrome b 595 -the high-spin cytochrome b component of the cytochrome bd complex - followed the changes in cytochrome d levels. CO difference spectra of both the wild-type strain and the cytochrome bd-deficient mutant revealed a haemoprotein with spectral characteristics similar to cytochrome o, the levels of which increased as the O2 supply was raised. These results are discussed with reference to previous reports of cytochrome changes in cells grown under N2-fixing conditions

CONVERGED VARIATIONAL QUANTUM SCATTERING RESULTS FOR THE 3-DIMENSIONAL F+D2 REACTION

Converged J=0 quantum reaction probabilities over the translational range 0.04 to 4.84 kcal/mol are computed for the 3D F+D2 reaction, using the log derivative version of the Kohn variational principle. Rotational distributions for the DF ν′=3 and ν′=4 product states formed from the ν=0, j=0 initial state are plotted. The results are considered in the light of available experimental and theoretical work on the F+H2, F+D2 and F+HD reactions. © 1990

CONVERGED VARIATIONAL QUANTUM SCATTERING RESULTS FOR THE 3-DIMENSIONAL F+HD REACTION

The log derivative version of the Kohn variational principle is used to calculate J=0 reaction probabilities and state-to-state time delays for the F+HD reaction, on the T5A potential energy surface, in the total energy range Etot=0.236 to 0.350 eV. While the computed reaction probabilities to H+DF are comparatively bland, those to D+HF show considerable resonant structure as a function of the scattering energy. For example, the computed state-to-state time delays for the predominant HF(v′=2) resonance et Etot=0.2575 eV imply the existence of a metastable collision complex with a half-life of about 0.1 ps. These results are discussed in the light of the high-resolution molecular beam experiments of Lee and coworkers and the bending corrected rotating linear model calculations of Hayes and Walker. © 1990