Elvin Hsing Geng and colleagues discuss mechanism mapping and its utility in conceptualizing and understanding how implementation strategies produce desired effects.
An intensive investigation of carbonaceous PM2.5 and TSP (total suspended particles) from Pudong (China) was conducted as part of the MIRAGE-Shanghai (Megacities Impact on Regional and Global ...Environment) experiment in 2009. Data for organic and elemental carbon (OC and EC), organic species, including C17 to C40 n-alkanes and 17 polycyclic aromatic hydrocarbons (PAHs), and stable carbon isotopes OC (δ13COC) and EC (δ13CEC) were used to evaluate the aerosols' temporal variations and identify presumptive sources. High OC/EC ratios indicated a large fraction of secondary organic aerosol (SOA); high char/soot ratios indicated stronger contributions to EC from motor vehicles and coal combustion than biomass burning. Diagnostic ratios of PAHs indicated that much of the SOA was produced via coal combustion. Isotope abundances (δ13COC = −24.5 ± 0.8‰ and δ13CEC = −25.1 ± 0.6‰) indicated that fossil fuels were the most important source for carbonaceous PM2.5 (particulate matter less than 2.5 micrometers in diameter), with lesser impacts from biomass burning and natural sources. An EC tracer system and isotope mass balance calculations showed that the relative contributions to total carbon from coal combustion, motor vehicle exhaust, and SOA were 41%, 21%, and 31%; other primary sources such as marine, soil and biogenic emissions contributed 7%. Combined analyses of OC and EC, n-alkanes and PAHs, and stable carbon isotopes provide a new way to apportion the sources of carbonaceous particles.
Ingrid Eshun-Wilson and colleagues summarize gaps in primary HIV implementation research methods and reporting, and propose areas for future methodological development.
Cancer research has been rightly and successfully focused on prevention, early detection, and identification of specific molecular targets that distinguish the malignant cells from the neighbouring ...benign cells. However, reducing lethal tissue injury caused by intensive chemoradiotherapy during treatment of late-stage metastatic cancers remains a key clinical challenge. Here we tested whether the induction of adult stem cells could repair chemoradiation-induced tissue injury and prolong overall survival in mice. We found that intestinal stem cells (ISCs) expressed Slit2 and its single-span transmembrane cell-surface receptor roundabout 1 (Robo1). Partial genetic deletion of Robo1 decreased ISC numbers and caused villus hypotrophy, whereas a Slit2 transgene increased ISC numbers and triggered villus hypertrophy. During lethal dosages of chemoradiation, administering a short pulse of R-spondin 1 (Rspo1; a Wnt agonist) plus Slit2 reduced ISC loss, mitigated gut impairment and protected animals from death, without concomitantly decreasing tumour sensitivity to chemotherapy. Therefore Rspo1 and Slit2 may act as therapeutic adjuvants to enhance host tolerance to aggressive chemoradiotherapy for eradicating metastatic cancers.
Three members of PLOS Medicine's editorial board who are leading researchers in implementation science define the characteristics of high-quality studies and invite their submission to the journal.
Abstract
The realization of controllable fermionic quantum systems via quantum simulation is instrumental for exploring many of the most intriguing effects in condensed-matter physics
1–3
. ...Semiconductor quantum dots are particularly promising for quantum simulation as they can be engineered to achieve strong quantum correlations. However, although simulation of the Fermi–Hubbard model
4
and Nagaoka ferromagnetism
5
have been reported before, the simplest one-dimensional model of strongly correlated topological matter, the many-body Su–Schrieffer–Heeger (SSH) model
6–11
, has so far remained elusive—mostly owing to the challenge of precisely engineering long-range interactions between electrons to reproduce the chosen Hamiltonian. Here we show that for precision-placed atoms in silicon with strong Coulomb confinement, we can engineer a minimum of six all-epitaxial in-plane gates to tune the energy levels across a linear array of ten quantum dots to realize both the trivial and the topological phases of the many-body SSH model. The strong on-site energies (about 25 millielectronvolts) and the ability to engineer gates with subnanometre precision in a unique staggered design allow us to tune the ratio between intercell and intracell electron transport to observe clear signatures of a topological phase with two conductance peaks at quarter-filling, compared with the ten conductance peaks of the trivial phase. The demonstration of the SSH model in a fermionic system isomorphic to qubits showcases our highly controllable quantum system and its usefulness for future simulations of strongly interacting electrons.
...in wicked problems, the elusive problem formulation precludes a shared understanding of success, or even progress, by stakeholders. ...in wicked problems, the absence of a shared agenda (and ...measures of progress) undermines aligned and effective action. ...the HIV response has used the cascade framework to define clear targets and extract commitments from elected leaders to meet those targets, thereby enabling measurable progress. The initiative has enrolled over 350 cities around the world—with the mayors of London, Paris, and other cosmopolitan cities all vocal advocates of 90–90–90. Because the cascade is reported, progress toward 90–90–90 can be widely assessed, creating some basis for accountability.
The COVID-19 vaccination campaign in the US has been immensely successful in vaccinating those who are receptive, further increases in vaccination rates however will require more innovative ...approaches to reach those who remain hesitant. Developing vaccination strategies that are modelled on what people want could further increase uptake. To inform COVID-19 vaccine distribution strategies that are aligned with public preferences we conducted a discrete choice experiment among the US public (N = 2,895) between March 15 to March 22, 2021. We applied sampling weights, evaluated mean preferences using mixed logit models, and identified latent class preference subgroups. On average, the public prioritized ease, preferring single to two dose vaccinations (mean preference: -0.29; 95%CI: -0.37 to -0.20), vaccinating once rather than annually (mean preference: -0.79; 95%CI: -0.89 to -0.70) and reducing waiting times at vaccination sites. Vaccine enforcement reduced overall vaccine acceptance (mean preference -0.20; 95%CI: -0.30 to -0.10), with a trend of increasing resistance to enforcement with increasing vaccine hesitancy. Latent class analysis identified four distinct preference phenotypes: the first prioritized inherent "vaccine features" (46.1%), the second were concerned about vaccine "service delivery" (8.8%), a third group desired "social proof" of vaccine safety and were susceptible to enforcement (13.2%), and the fourth group were "indifferent" to vaccine and service delivery features and resisted enforcement (31.9%). This study identifies several critical insights for the COVID-19 public health response. First, identifying preference segments is essential to ensure that vaccination services meet the needs of diverse population subgroups. Second, making vaccination easy and promoting autonomy by simplifying services and offering the public choices (where feasible) may increase uptake in those who remain deliberative. And, third vaccine mandates have the potential to increase vaccination rates in susceptible groups but may simultaneously promote control aversion and resistance in those who are most hesitant.
Evidence, in multiple forms, is a foundation of implementation science. For public health and clinical practice, evidence includes the following: type 1 evidence on etiology and burden; type 2 ...evidence on effectiveness of interventions; and type 3: evidence on dissemination and implementation (D&I) within context. To support a vision for development and use of evidence in D&I science that is more comprehensive and equitable (particularly for type 3 evidence), this article aims to clarify concepts of evidence, summarize ongoing debates about evidence, and provide a set of recommendations and tools/resources for addressing the "how-to" in filling evidence gaps most critical to advancing implementation science.
Because current conceptualizations of evidence have been relatively narrow and insufficiently characterized in our opinion, we identify and discuss challenges and debates about the uses, usefulness, and gaps in evidence for implementation science. A set of questions is proposed to assist in determining when evidence is sufficient for dissemination and implementation. Intersecting gaps include the need to (1) reconsider how the evidence base is determined, (2) improve understanding of contextual effects on implementation, (3) sharpen the focus on health equity in how we approach and build the evidence-base, (4) conduct more policy implementation research and evaluation, and (5) learn from audience and stakeholder perspectives. We offer 15 recommendations to assist in filling these gaps and describe a set of tools for enhancing the evidence most needed in implementation science.
To address our recommendations, we see capacity as a necessary ingredient to shift the field's approach to evidence. Capacity includes the "push" for implementation science where researchers are trained to develop and evaluate evidence which should be useful and feasible for implementers and reflect community or stakeholder priorities. Equally important, there has been inadequate training and too little emphasis on the "pull" for implementation science (e.g., training implementers, practice-based research). We suggest that funders and reviewers of research should adopt and support a more robust definition of evidence. By critically examining the evolving nature of evidence, implementation science can better fulfill its vision of facilitating widespread and equitable adoption, delivery, and sustainment of scientific advances.
Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the ...burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART.
We searched databases between 1 January 2010 and 9 November 2021 to identify randomized controlled trials (RCTs) and observational studies that compared reduced (6- to 12-monthly) clinical consultation or ART refill appointment frequency to 3- to 6-monthly appointments for patients established on ART. We assessed methodological quality and real-world relevance, and used Mantel-Haenszel methods to generate pooled risk ratios (RRs) with 95% confidence intervals for retention, viral suppression, and mortality. We evaluated heterogeneity quantitatively and qualitatively, and overall evidence certainty using GRADE. Searches yielded 3,955 records, resulting in 10 studies (6 RCTs, 3 observational studies, and 1 study contributing observational and RCT data) representing 15 intervention arms with 33,599 adults (≥16 years) in 8 sub-Saharan African countries. Reduced frequency clinical consultations occurred at health facilities, while reduced frequency ART refills were delivered through facility or community pharmacies and adherence groups. Studies were highly pragmatic, except for some study settings and resources used in RCTs. Among studies comparing reduced clinical consultation frequency (6- or 12-monthly) to 3-monthly consultations, there appeared to be no difference in retention (RR 1.01, 95% CI 0.97-1.04, p = 0.682, 8 studies, low certainty), and this finding was consistent across 6- and 12-monthly consultation intervals and delivery strategies. Viral suppression effect estimates were markedly influenced by under-ascertainment of viral load outcomes in intervention arms, resulting in inconclusive evidence. There was similarly insufficient evidence to draw conclusions on mortality (RR 1.12, 95% CI 0.75-1.66, p = 0.592, 6 studies, very low certainty). For ART refill frequency, there appeared to be little to no difference in retention (RR 1.01, 95% CI 0.98-1.06, p = 0.473, 4 RCTs, moderate certainty) or mortality (RR 1.45, 95% CI 0.63-3.35, p = 0.382, 4 RCTs, low certainty) between 6-monthly and 3-monthly visits. Similar to the analysis for clinical consultations, although viral suppression appeared to be better in 3-monthly arms, effect estimates were markedly influence by under-ascertainment of viral load outcomes in intervention arms, resulting in overall inclusive evidence. This systematic review was limited by the small number of studies available to compare 12- versus 6-monthly clinical consultations, insufficient data to compare implementation strategies, and lack of evidence for children, key populations, and low- and middle-income countries outside of sub-Saharan Africa.
Based on this synthesis, extending clinical consultation intervals to 6 or 12 months and ART dispensing intervals to 6 months appears to result in similar retention to 3-month intervals, with less robust conclusions for viral suppression and mortality. Future research should ensure complete viral load outcome ascertainment, as well as explore mechanisms of effect, outcomes in other populations, and optimum delivery and monitoring strategies to ensure widespread applicability of reduced frequency visits across settings.
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