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Book
Patient-Reported Barriers to Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis
Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.
We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children.
Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence.
Journal Article
Beyond grief : sculpture and wonder in the Gilded Age cemetery
\"This book attempts to set out at least part of the story of how high-style funerary sculpture functioned at the turn of the twentieth century and in the decades immediately after, a subject little investigated to date by scholars. These monuments have not been considered in terms of their wider context and shifting use as objects of consolation, power, and multisensory mystery and wonder. Rather, they have mostly been considered as oddities, a part of an individual artist's oeuvre, a detail of a patron's biography, or as local civic cemetery history. Why did new forms--many of them now produced in bronze rather than stone and placed in architectural settings--arise just at this time, and how did they mesh or clash with the sensibilities of their era? Why was there a gap between the intention of these elite patrons and artists, whose lives were often intertwined in a closed circle, and the way some public audiences received them through the filter of the mass media?\"-- Provided by publisher.
Book
Earliest land plants created modern levels of atmospheric oxygen
The progressive oxygenation of the Earth’s atmosphere was pivotal to the evolution of life, but the puzzle of when and how atmospheric oxygen (O₂) first approached modern levels (∼21%) remains unresolved. Redox proxy data indicate the deep oceans were oxygenated during 435–392 Ma, and the appearance of fossil charcoal indicates O₂ >15–17% by 420–400 Ma. However, existing models have failed to predict oxygenation at this time. Here we show that the earliest plants, which colonized the land surface from ∼470 Ma onward, were responsible for this mid-Paleozoic oxygenation event, through greatly increasing global organic carbon burial—the net long-term source of O₂. We use a trait-based ecophysiological model to predict that cryptogamic vegetation cover could have achieved ∼30% of today’s global terrestrial net primary productivity by ∼445 Ma. Data from modern bryophytes suggests this plentiful early plant material had a much higher molar C:P ratio (∼2,000) than marine biomass (∼100), such that a given weathering flux of phosphorus could support more organic carbon burial. Furthermore, recent experiments suggest that early plants selectively increased the flux of phosphorus (relative to alkalinity) weathered from rocks. Combining these effects in a model of long-term biogeochemical cycling, we reproduce a sustained +2‰ increase in the carbonate carbon isotope (δ13C) record by ∼445 Ma, and predict a corresponding rise in O₂ to present levels by 420–400 Ma, consistent with geochemical data. This oxygen rise represents a permanent shift in regulatory regime to one where fire-mediated negative feedbacks stabilize high O₂ levels.
Journal Article
An Overview of Precision Oncology Basket and Umbrella Trials for Clinicians
With advancements in biomarkers and momentum in precision medicine, biomarker-guided trials such as basket trials and umbrella trials have been developed under the master protocol framework. A master protocol refers to a single, over-arching design developed to evaluate multiple hypotheses with the general goal of improving the efficiency of trial evaluation. One type of master protocol is the basket trial, in which a targeted therapy is evaluated for multiple diseases that share com-mon molecular alterations or risk factors that may help predict whether the patients will respond to the given therapy. Another variant of a master protocol is the umbrella trial, in which multiple targeted therapies are evaluated for a single disease that is stratified into multiple subgroups based on different molecular or other predictive risk factors. Both designs follow the core principle of precision medicine-to tailor intervention strategies based on the patient's risk factor(s) that can help predict whether they will respond to a specific treatment. There have been increasing num-bers of basket and umbrella trials, but they are still poorly understood. This article re-views common characteristics of basket and umbrella trials, key trials and recent US Food and Drug Administration approvals for precision oncology, and important con-siderations for clinical readers when critically evaluating future publications on bas-ket trials and umbrella trials and for researchers when designing these clinical trials.
Journal Article
Magnetically-driven phase transformation strengthening in high entropy alloys
CrCoNi alloy exhibits a remarkable combination of strength and plastic deformation, even superior to the CrMnFeCoNi high-entropy alloy. We connect the magnetic and mechanical properties of CrCoNi, via a magnetically tunable phase transformation. While both alloys crystallize as single-phase face-centered-cubic (fcc) solid solutions, we find a distinctly lower-energy phase in CrCoNi alloy with a hexagonal close-packed (hcp) structure. Comparing the magnetic configurations of CrCoNi with those of other equiatomic ternary derivatives of CrMnFeCoNi confirms that magnetically frustrated Mn eliminates the fcc-hcp energy difference. This highlights the unique combination of chemistry and magnetic properties in CrCoNi, leading to a fcc-hcp phase transformation that occurs only in this alloy, and is triggered by dislocation slip and interaction with internal boundaries. This phase transformation sets CrCoNi apart from the parent quinary, and its other equiatomic ternary derivatives, and provides a new way for increasing strength without compromising plastic deformation.
Medium entropy alloy CoCrNi has better mechanical properties than high entropy alloys such as CrMnFeCoNi, but why that is remains unclear. Here, the authors show that a nanostructured phase at lattice defects in CoCrNi causes its extraordinary properties, while it is magnetically frustrated and suppressed in CrMnFeCoNi.
Journal Article
Harnessing global fisheries to tackle micronutrient deficiencies
Micronutrient deficiencies account for an estimated one million premature deaths annually, and for some nations can reduce gross domestic product
1
,
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by up to 11%, highlighting the need for food policies that focus on improving nutrition rather than simply increasing the volume of food produced
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. People gain nutrients from a varied diet, although fish—which are a rich source of bioavailable micronutrients that are essential to human health
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—are often overlooked. A lack of understanding of the nutrient composition of most fish
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and how nutrient yields vary among fisheries has hindered the policy shifts that are needed to effectively harness the potential of fisheries for food and nutrition security
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. Here, using the concentration of 7 nutrients in more than 350 species of marine fish, we estimate how environmental and ecological traits predict nutrient content of marine finfish species. We use this predictive model to quantify the global spatial patterns of the concentrations of nutrients in marine fisheries and compare nutrient yields to the prevalence of micronutrient deficiencies in human populations. We find that species from tropical thermal regimes contain higher concentrations of calcium, iron and zinc; smaller species contain higher concentrations of calcium, iron and omega-3 fatty acids; and species from cold thermal regimes or those with a pelagic feeding pathway contain higher concentrations of omega-3 fatty acids. There is no relationship between nutrient concentrations and total fishery yield, highlighting that the nutrient quality of a fishery is determined by the species composition. For a number of countries in which nutrient intakes are inadequate, nutrients available in marine finfish catches exceed the dietary requirements for populations that live within 100 km of the coast, and a fraction of current landings could be particularly impactful for children under 5 years of age. Our analyses suggest that fish-based food strategies have the potential to substantially contribute to global food and nutrition security.
Nutrient content analyses of marine finfish and current fisheries landings show that fish have the potential to substantially contribute to global food and nutrition security by alleviating micronutrient deficiencies in regions where they are prevalent.
Journal Article