Challenges for research uptake for health policymaking and practice in low- and middle-income countries: a scoping review.

BACKGROUND: An estimated 85% of research resources are wasted worldwide, while there is growing demand for context-based evidence-informed health policymaking. In low- and middle-income countries (LMICs), research uptake for health policymaking and practice is even lower, while little is known about the barriers to the translation of health evidence to policy and local implementation. We aimed to compile the current evidence on barriers to uptake of research in health policy and practice in LMICs using scoping review. METHODS: The scoping review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses-extension for Scoping Reviews (PRISMA-ScR) and the Arksey and O'Malley framework. Both published evidence and grey literature on research uptake were systematically searched from major databases (PubMed, Cochrane Library, CINAHL (EBSCO), Global Health (Ovid)) and direct Google Scholar. Literature exploring barriers to uptake of research evidence in health policy and practice in LMICs were included and their key findings were synthesized using thematic areas to address the review question. RESULTS: A total of 4291 publications were retrieved in the initial search, of which 142 were included meeting the eligibility criteria. Overall, research uptake for policymaking and practice in LMICs was very low. The challenges to research uptake were related to lack of understanding of the local contexts, low political priority, poor stakeholder engagement and partnership, resource and capacity constraints, low system response for accountability and lack of communication and dissemination platforms. CONCLUSION: Important barriers to research uptake, mainly limited contextual understanding and low participation of key stakeholders and ownership, have been identified. Understanding the local research and policy context and participatory evidence production and dissemination may promote research uptake for policy and practice. Institutions that bridge the chasm between knowledge formation, evidence synthesis and translation may play critical role in the translation process.

Systematic review of the diagnosis and management of necrotising otitis externa: Highlighting the need for high-quality research.

OBJECTIVES: To present a systematic review and critical analysis of clinical studies for necrotising otitis externa (NOE), with the aim of informing best practice for diagnosis and management. DESIGN: Medline, Embase, Cochrane Library and Web of Science were searched from database inception until 30 April 2021 for all clinical articles on NOE. The review was registered on PROSPERO (ID: CRD42020128957) and conducted in accordance with PRISMA guidelines. RESULTS: Seventy articles, including 2274 patients were included in the final synthesis. Seventy-three percent were retrospective case series; the remainder were of low methodological quality. Case definitions varied widely. Median patient age was 69.2 years; 68% were male, 84% had diabetes and 10% had no reported immunosuppressive risk factor. Otalgia was almost universal (96%), with granulation (69%) and oedema (76%) the commonest signs reported. Pseudomonas aeruginosa was isolated in 62%, but a range of bacterial and fungal pathogens were reported and 14% grew no organism. Optimal imaging modality for diagnosis or follow-up was unclear. Median antimicrobial therapy duration was 7.2 weeks, with no definitive evidence for optimal regimens. Twenty-one percent had surgery with widely variable timing, indication, or procedure. One-year disease-specific mortality was 2%; treatment failure and relapse rates were 22% and 7%, respectively. CONCLUSION: There is a lack of robust, high-quality data to support best practice for diagnosis and management for this neglected condition. A minimum set of reporting requirements is proposed for future studies. A consensus case definition is urgently needed to facilitate high-quality research.

Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder.

Ethanol exposure during the early stages of embryonic development can lead to a range of morphological and behavioral differences termed fetal alcohol spectrum disorders (FASDs). In a zebrafish model, we have shown that acute ethanol exposure at 8-10 hr postfertilization (hpf), a critical time of development, produces birth defects similar to those clinically characterized in FASD. Dysregulation of the Sonic hedgehog (Shh) pathway has been implicated as a molecular basis for many of the birth defects caused by prenatal alcohol exposure. We observed in zebrafish embryos that shh expression was significantly decreased by ethanol exposure at 8-10 hpf, while smo expression was much less affected. Treatment of zebrafish embryos with SAG or purmorphamine, small molecule Smoothened agonists that activate Shh signaling, ameliorated the severity of ethanol-induced developmental malformations including altered eye size and midline brain development. Furthermore, this rescue effect of Smo activation was dose dependent and occurred primarily when treatment was given after ethanol exposure. Markers of Shh signaling (gli1/2) and eye development (pax6a) were restored in embryos treated with SAG post-ethanol exposure. Since embryonic ethanol exposure has been shown to produce later-life neurobehavioral impairments, juvenile zebrafish were examined in the novel tank diving test. Our results further demonstrated that in zebrafish embryos exposed to ethanol, SAG treatment was able to mitigate long-term neurodevelopmental impairments related to anxiety and risk-taking behavior. Our results indicate that pharmacological activation of the Shh pathway at specific developmental timing markedly diminishes the severity of alcohol-induced birth defects.

Collection and Utilization of Patient-Reported Outcome Measures in a Colorectal Surgery Clinic.

INTRODUCTION: The routine collection of patient-reported outcome measures (PROMs) promises to improve patient care. However, in colorectal surgery, PROMs are uncommonly collected outside of clinical research studies and rarely used in clinical care. We designed and implemented a quality improvement project with the goals of routinely collecting PROMs and increasing the frequency that PROMs are utilized by colorectal surgeons in clinical practice. METHODS: This mixed-methods, quality improvement project was conducted in the colorectal surgery clinic of a tertiary academic medical center. Patients were administered up to five PROMs before each appointment. PROM completion rates were measured. Additionally, we performed two educational interventions to increase utilization of our electronic health record's PROM dashboard by colorectal surgeons. Utilization rates and attitudes toward the PROM dashboard were measured. RESULTS: Overall, patients completed 3600 of 3977 (90.9%) administered PROMs during the study period. At baseline, colorectal surgeons reviewed 6.7% of completed PROMs. After two educational interventions, this increased to 39.3% (P = 0.004). Colorectal surgeons also felt that the PROM dashboard was easier to use. Barriers to greater PROM dashboard utilization included poor user interface/user experience and a perceived lack of knowledge, time, and relevance. CONCLUSIONS: The collection of PROMs in colorectal surgery clinics is feasible and can result in high PROM completion rates. Educational interventions can improve the utilization of PROMs by colorectal surgeons in clinical practice. Our experience collecting PROMs through this quality improvement initiative can serve as a template for other colorectal surgery clinics interested in collecting and utilizing data from PROMs.

Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

BACKGROUND: This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). METHODS: Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. RESULTS: About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively). CONCLUSION: Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

Phylogeny and historical biogeography of the pantropical genus Parkia (Leguminosae, Caesalpinioideae, mimosoid clade).

Parkia R.Br. (Leguminosae, Caesalpinioideae, mimosoid clade) is a pantropical genus with approximately 35 recognized species in three taxonomic sections (Parkia, Platyparkia and Sphaeroparkia), distributed widely in tropical forests and savannas in South and Central America, Africa-Madagascar and the Indo-Pacific region. In this study, phylogenetic analyses (Maximum Likelihood and Bayesian Inference), ancestral area and habitat estimations were performed using chloroplast (matK, trnL, psbA-trnH and rps16-trnQ) and nuclear (ITS/18S/26S) DNA sequences for the purpose of testing the monophyly of Parkia and inferring the geographic origin of the genus and times of divergence of the various lineages. This enabled investigation of factors that may have influenced its diversification in both hemispheres. Our results support the monophyly of the genus. A fossil-calibrated Bayesian analysis dated the Parkia crown node to the Miocene (at c. 18.85 Ma). Biogeographic analysis reconstructed an origin in the lowlands rainforests (terra firme) in Amazonia with subsequent radiation in the Neotropical region from the Miocene onwards, with dispersion events as far as Central America, and the Atlantic Forest and the cerrado of Brazil. A single dispersion from the Neotropics to the Paleotropics is hypothesised, with subsequent smaller radiations in Africa-Madagascar and the Indo-Pacific (crown ages 3.79 and 5.15 Ma respectively). Factors that may have influenced the radiation and speciation of Parkia include the elevation of the Andes (especially in the Miocene), and more recently the closing of the Panama gap in Neotropics, the climatic fluctuations of the Pleistocene influenced the diversification of species on both continents. The elevation of the Sunda Shelf in Indo-Pacific region during the last glacial maximum (LGM) appears to be the main driving force for speciation in that region. In Africa, the low number of species may be related to extinction processes.

Appraising research policy instrument mixes: a multicriteria mapping study in six European countries of diagnostic innovation to manage antimicrobial resistance.

This article provides prospective appraisal of key policy instruments intended to stimulate innovation to combat antimicrobial resistance (AMR). AMR refers to the ability of microbes to evolve resistance to those treatments designed to kill them, and is associated with the overuse or misuse of medicines such as antibiotics. AMR is an emerging global challenge with major implications for healthcare and society as a whole. Diagnostic tests for infectious diseases can guide decision making when prescribing medicines, so reducing inappropriate drug use. In the context of growing international interest in policies to stimulate innovation in AMR diagnostics, this study uses multicriteria mapping (MCM) to appraise a range of policy instruments in order to understand their potential performance while also highlighting the uncertainties that stakeholders hold about such interventions in complex contexts. A contribution of the article is the demonstration of a novel method to analyse and visualise MCM data in order to reveal stakeholder inclinations towards particular options while exploring interviewees' uncertainties about the effectiveness of each instrument's design or implementation. The article reports results from six European countries (Germany, Greece, Italy, the Netherlands, Spain and the UK). The findings reveal which policy instruments are deemed most likely to perform well, and why, across stakeholder groups and national settings, with areas of common ground and difference being identified. Importantly, the conclusions presented here differ from prominent policy discourse, with international implications for the design of mixes of policy instruments to combat AMR. Strategic and practical methodological implications also emerge for general appraisal of innovation policy instrument mixes.

Stochastic rounding and reduced-precision fixed-point arithmetic for solving neural ordinary differential equations.

Although double-precision floating-point arithmetic currently dominates high-performance computing, there is increasing interest in smaller and simpler arithmetic types. The main reasons are potential improvements in energy efficiency and memory footprint and bandwidth. However, simply switching to lower-precision types typically results in increased numerical errors. We investigate approaches to improving the accuracy of reduced-precision fixed-point arithmetic types, using examples in an important domain for numerical computation in neuroscience: the solution of ordinary differential equations (ODEs). The Izhikevich neuron model is used to demonstrate that rounding has an important role in producing accurate spike timings from explicit ODE solution algorithms. In particular, fixed-point arithmetic with stochastic rounding consistently results in smaller errors compared to single-precision floating-point and fixed-point arithmetic with round-to-nearest across a range of neuron behaviours and ODE solvers. A computationally much cheaper alternative is also investigated, inspired by the concept of dither that is a widely understood mechanism for providing resolution below the least significant bit in digital signal processing. These results will have implications for the solution of ODEs in other subject areas, and should also be directly relevant to the huge range of practical problems that are represented by partial differential equations. This article is part of a discussion meeting issue 'Numerical algorithms for high-performance computational science'.

Synthesis, Structure, and Bonding of d3 Molybdenum-Oxo Complexes.

Reduction of d2 metal-oxo ions of the form [MO(PP)2 Cl]+ (M=Mo, W; PP=chelating diphosphine) produces d3 MO(PP)2 Cl complexes, which include the first isolated examples in group 6. The stability and reactivity of the MO(PP)2 Cl compounds are found to depend upon the steric bulk of the phosphine ligands: derivatives with bulky phosphines that shield the oxo ligand are stable enough to be isolated, whereas those with phosphines that leave the oxo ligand exposed are more reactive and observed transiently. Magnetic measurements and DFT calculations on MoO(dppe)2 Cl indicate the d3 compounds are low spin with a 2 [(dxy )2 (π*(MoO))1 ] configuration. X-ray crystallographic and vibrational-spectroscopic studies on d2 and d3 [MoO(dppe)2 Cl]0/+ establish that the d3 compound possesses a reduced M-O bond order and significantly longer Mo-O bond, accounting for its greater reactivity. These results indicate that the oxo-centered reactivity of d3 complexes may be controlled through ligand variation.

Surgical management of primary colonic lymphoma: Big data for a rare problem.

BACKGROUND AND OBJECTIVES: Primary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short-term outcomes, and five-year survival of patients undergoing nonpalliative surgery for PCL. METHODS: We performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis. RESULTS: We identified 2153 patients. Median patient age was 68. Diffuse large B-cell lymphoma accounted for 57% of tumors. 30- and 90-Day mortality were high (5.6% and 11.1%, respectively). Thirty-nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5-year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07-1.51; P = .01). CONCLUSIONS: Patients undergoing surgery for PCL have high rates of margin positivity and high short-term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.

Are we close to knowing the plant diversity of the Amazon?

Amazonia is often cited as having the most diverse flora on the planet. However, the total number of species of higher plants in the region has been largely a matter of guesswork. Some recent publications have estimated the total number of species present, which indicate a lower overall diversity than was estimated in the past. However, analysis of the sampling density across the region, and data from various sources suggest that there may be reason why the recent figures may be considerable underestimates. I believe that much more investment in extensive collecting of quality plant specimens is needed to encounter the very large number of rare and local species that might never have been collected. Unfortunately the tendencies of investment in botany, in terms of geography and types of project, suggest that we will probably not be able to accurately assess the real diversity of the region.

Evaluation of extended antibiotic prophylaxis in patients undergoing indicated non-cosmetic panniculectomy at the time of gynecologic surgery.

BACKGROUND: Panniculectomy at time of gynecologic surgery is used to improve visualization and prevent major complications in morbidly obese patients. We examine the role of extended antibiotic prophylaxis in prevention of surgical site infections (SSI), specifically based on patient risk factors (hypertension, diabetes, smoking). METHODS: A prospective cohort study of all women who underwent panniculectomy at the time of gynecologic surgery from September 2014 to March 2016 at a university-affiliated hospital. The EAP cohort received standard antibiotics (cefazolin, 2 g) and continued oral antibiotic (doxycycline) for 10 days afterwards. Patients in this cohort were compared to historical controls from the same institution from 1990 to 2014. Specific attention was paid to the reduction of SSIs in patients with hypertension, diabetes, and a history of smoking. RESULTS: The mean age was 56.0 ± 12.6 years, and mean body mass index 44.5 ± 9.3 kg/m2 (range 31-63.4 kg/m2 ). The EAP cohort experienced fewer surgical-site infections overall, however these results were not significantly decreased from the historical controls, (13/56 [23.2%] vs 94/300 [31.3%]; P = 0.469). CONCLUSION: Though initially promising, extended antibiotic prophylaxis did not reduce surgical site infections in the obese women after indicated non-cosmetic panniculectomy at the time of gynecologic surgery.

Panel Size, Clinician Time in Clinic, and Access to Appointments.

Large panel sizes are often held responsible for worse access to appointments in primary care. We evaluated the relationship between appointment backlog, panel size, and primary care clinician time in clinic, using Spearman correlation and multiple regression in a retrospective analysis. We found no independent association between panel size and days until third next available appointment, but larger panel size adjusted for clinician time in clinic was associated with worse access. Less clinician time in clinic was independently associated with longer backlogs for appointments. Our findings suggest that patients of part-time clinicians may be less likely to obtain timely appointments than patients of fulltime clinicians, regardless of panel size.

Electron-transfer sensitization of H2 oxidation and CO2 reduction catalysts using a single chromophore.

Energy-storing artificial-photosynthetic systems for CO2 reduction must derive the reducing equivalents from a renewable source rather than from sacrificial donors. To this end, a homogeneous, integrated chromophore/two-catalyst system is described that is thermodynamically capable of photochemically driving the energy-storing reverse water-gas shift reaction (CO2 + H2 → CO + H2O), where the reducing equivalents are provided by renewable H2. The system consists of the chromophore zinc tetraphenylporphyrin (ZnTPP), H2 oxidation catalysts of the form [Cp(R)Cr(CO)3](-), and CO2 reduction catalysts of the type Re(bpy-4,4'-R2)(CO)3Cl. Using time-resolved spectroscopic methods, a comprehensive mechanistic and kinetic picture of the photoinitiated reactions of mixtures of these compounds has been developed. It has been found that absorption of a single photon by broadly absorbing ZnTPP sensitizes intercatalyst electron transfer to produce the substrate-active forms of each. The initial photochemical step is the heretofore unobserved reductive quenching of the low-energy T1 state of ZnTPP. Under the experimental conditions, the catalytically competent state decays with a second-order half-life of ∼15 µs, which is of the right magnitude for substrate trapping of sensitized catalyst intermediates.

Recurrent Vulvar Carcinoma in a Skin Graft: A Case Reiort and Review of the Literature.

In recentyears, theincidence ofvul- var carcinoma has increased over 400%, specifically in the population of young women. We present a patient with an extensive history of recurrent vulvar carcinoma in situ who underwent multiple surgi- cal procedures and subsequent reconstruction with a skin graft, who then returned with a rare recur- rence in the graft. Multiple hypotheses have been proposedto explain the recurrence ofthis type ofcar- cinoma; however, none provides a solid explanation. It has been noted that the increase in the incidence of vulvar cancer correlates with the increased incidence of HPV infection; the relationship between the two has been well-established. In conclusion, we recommend close and long-term follow-up for high-risk patients with this type of neoplasm.

Isolation and trans-differentiation of mesenchymal stromal cells into smooth muscle cells: Utility and applicability for cell-sheet engineering.

BACKGROUND: Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) have shown potential to differentiate into various cell types, including smooth muscle cells (SMCs). The extracellular matrix (ECM) represents an appealing and readily available source of SMCs for use in tissue engineering. In this study, we hypothesized that the ECM could be used to induce MSC differentiation to SMCs for engineered cell-sheet construction. METHODS: Primary MSCs were isolated from the BM of Wistar rats, transferred and cultured on dishes coated with 3 different types of ECM: collagen type IV (Col IV), fibronectin (FN), and laminin (LM). Primary MSCs were also included as a control. The proportions of SMC (a smooth muscle actin [aSMA] and SM22a) and MSC markers were examined with flow cytometry and Western blotting, and cell proliferation rates were also quantified. RESULTS: Both FN and LM groups were able to induce differentiation of MSCs toward smooth muscle-like cell types, as evidenced by an increase in the proportion of SMC markers (aSMA; Col IV 42.3 ± 6.9%, FN 65.1 ± 6.5%, LM 59.3 ± 7.0%, Control 39.9 ± 3.1%; P = 0.02, SM22; Col IV 56.0 ± 7.7%, FN 74.2 ± 6.7%, LM 60.4 ± 8.7%, Control 44.9 ± 3.6%) and a decrease in that of MSC markers (CD105: Col IV 64.0 ± 5.2%, FN 57.6 ± 4.0%, LM 60.3 ± 7.0%, Control 85.3 ± 4.2%; P = 0.03). The LM group showed a decrease in overall cell proliferation, whereas FN and Col IV groups remained similar to control MSCs (Col IV, 9.0 ± 2.3%; FN, 9.8 ± 2.5%; LM, 4.3 ± 1.3%; Control, 9.8 ± 2.8%). CONCLUSIONS: Our findings indicate that ECM selection can guide differentiation of MSCs into the SMC lineage. Fibronectin preserved cellular proliferative capacity while yielding the highest proportion of differentiated SMCs, suggesting that FN-coated materials may be facilitate smooth muscle tissue engineering.

Axial Ligand Effects on the Structures of Self-Assembled Gallium-Porphyrin Monolayers on Highly Oriented Pyrolytic Graphite.

Monolayers of five-coordinate gallium octaethylporphyrin complexes (Ga(OEP)X; X = Cl, Br, I, O3SCF3, CCPh) on highly oriented pyrolytic graphite were studied at the solid-liquid (1-phenyloctane) interface using scanning tunneling microscopy (STM) to probe the dependence of their properties on the nature of the axial X ligand. Density functional theory calculations of the gas-phase structures of the free molecules reveal that the gallium atom is positioned above the plane of the porphyrin macrocycle, with this pyramidal distortion increasing in magnitude according to X = O3SCF3 (displacement = 0.35 Å) < Cl, Br, I (∼0.47 Å) < CCPh (0.54 Å). All compounds exhibit pseudohexagonal close-packed structures in which the porphyrin is oriented coplanar with the surface and the axial ligand is oriented perpendicular to it, and with unit-cell parameters that are within experimental error of each other (a, b = 1.34 (3)-1.39 (2) nm, Γ = 66 (2)-68 (1)°). In contrast to these close similarities, the stabilities of the monolayers are sensitive to the nature of the axial ligand: the monolayers of Ga(OEP)(O3SCF3) and Ga(OEP)(CCPh) exhibit damage during the STM experiment upon repeated scanning and upon toggling the sign of the bias potential, but monolayers of Ga(OEP)Cl, Ga(OEP)Br, and Ga(OEP)I do not. A second important ligand-influenced property is that Ga(OEP)I forms bilayer structures, whereas the other Ga(OEP)X compounds form monolayers exclusively under identical conditions. The top layer of the Ga(OEP)I bilayer is oriented with the iodo ligand directed away from the surface, like the bottom layer, but the molecules pack in a square, lower-density geometry. The comparatively large polarizability of the iodo ligand is suggested to be important in stabilizing the bilayer structure.