Minimal Reductions Research Articles

No-Poaching Clauses, Job Concentration and Wages: A Natural Experiment Generated by a State Attorney General

We use a natural experiment to perform the first empirical analysis of the widely-claimed effect of no-poaching clauses on job-market concentration and wages. In 2018, the Washington State Attorney General obtained agreements from dozens of quick-service restaurant brands, encompassing thousands of restaurants across the United States, to stop enforcing no-poaching clauses. We use the unexpected, nation-wide enforcement action to identify the effect of no-poaching clauses on job-concentration and wages in job markets covering 3,035 franchised quick-service restaurants in Rhode Island and Florida. We find the elimination of no-poaching clauses causes minimal reductions in job concentration and no increase in wages.

Sarco-Endoplasmic Reticulum Calcium Release Model Based on Changes in the Luminal Calcium Content.

The sarcoplasmic/endoplasmic reticulum (SR/ER) is the main intracellular calcium (Ca2+) pool in muscle and non-muscle eukaryotic cells, respectively. The reticulum accumulates Ca2+ against its electrochemical gradient by the action of sarco/endoplasmic reticulum calcium ATPases (SERCA pumps), and the capacity of this Ca2+ store is increased by the presence of Ca2+ binding proteins in the lumen of the reticulum. A diversity of physical and chemical signals, activate the main Ca2+ release channels, i.e. ryanodine receptors (RyRs) and inositol (1, 4, 5) trisphosphate receptors (IP3Rs), to produce transient elevations of the cytoplasmic calcium concentration ([Ca2+]i) while the reticulum is being depleted of Ca2+. This picture is incomplete because it implies that the elements involved in the Ca2+ release process are acting alone and independently of each other. However, it appears that the Ca2+ released by RyRs and IP3Rs is trapped in luminal Ca2+ binding proteins (Ca2+ lattice), which are associated with these release channels, and the activation of these channels appears to facilitate that the trapped Ca2+ ions become available for release. This situation makes the initial stage of the Ca2+ release process a highly efficient one; accordingly, there is a large increase in the [Ca2+]i with minimal reductions in the bulk of the free luminal SR/ER [Ca2+] ([Ca2+]SR/ER). Additionally, it has been shown that active SERCA pumps are required for attaining this highly efficient Ca2+ release process. All these data indicate that Ca2+ release by the SR/ER is a highly regulated event and not just Ca2+ coming down its electrochemical gradient via the open release channels. One obvious advantage of this sophisticated Ca2+ release process is to avoid depletion of the ER Ca2+ store and accordingly, to prevent the activation of ER stress during each Ca2+ release event.

Tungsten doping for stabilization of Li[Ni0.90Co0.05Mn0.05]O2 cathode for Li-ion battery at high voltage

0.5-mol% and 1.0-mol% W-doped Li[Ni0.90Co0.05Mn0.05]O2 cathodes are synthesized by introducing W in the [Ni0.90Co0.05Mn0.05](OH)2 precursor stage. The W doping considerably improves the cycling stability at 2.7–4.3 V (96% at 100 cycles) and even at 4.4 V (94.5% at 100 cycles) with minimal reductions in the initial capacity (235 mA h g−1 at 4.4 V) of the 1.0-mol% W-doped. The superior chemical stability of the 1.0-mol% W-doped Li[Ni0.90Co0.05Mn0.05]O2 cathode is confirmed by an accelerated thermal aging test (storing of the highly delithiated cathode in the electrolyte at 60 °C). The observed improvement in the performance of the W-doped Li[Ni0.90Co0.05Mn0.05]O2 cathode is attributed mainly to bulk structure stabilization through the reduction in the internal strain, suppressing the detrimental formation of microcracks. Moreover, the spinel-like phase on the periphery of the primary particles acts as a buffer to protect the particle interior from the electrolyte attack. The applicability of the 1.0-mol% W-doped Li[Ni0.90Co0.05Mn0.05]O2 cathode for a high-energy-density Li-ion battery for electric vehicles is partially verified as it maintains 89% of its initial capacity after 500 cycles in a full-cell cycled at a high voltage of 4.3 V (vs. graphite), compared to the value of only 60% for the pristine cathode.

IDENTIFICATION OF GENETIC PATHWAYS CONTROLLING RESISTANCE TO STANDARD COMBINATION CHEMOTHERAPY IN ACUTE MYELOID LEUKAEMIA

Genetic aberrations and clonal evolution underpin chemoresistant and relapsed acute myeloid leukaemia (AML). We used a genome-wide CRISPR knock-out screen to identify genes which mediate resistance to Cytarabine (AraC) and Doxorubicin (Dox) in AML, informing combination therapies to potentially circumvent resistance. Cas9-expressing human AML cell lines, OCI-AML3 and MV4-11, were transduced with the Brunello gRNA library and treated with continuous or intermittent Dox/AraC (D/A), at synergistic doses sufficient to eliminate non-transduced controls, but allow outgrowth of resistant library-transduced populations. In resistant populations, gRNAs targeting AraC metabolism components, including deoxycytidine kinase (DCK) were enriched. Additionally, cyclin-dependent kinase inhibitor 2a (CDKN2A) and checkpoint kinase 2 (CHEK2) were major hits. CDKN2A and CHEK2 mediate apoptosis and cell cycle arrest in response to DNA damage and are clinically relevant in AML. In competition assays, CDKN2A and CHK2 inactivation by CRISPR led to a survival advantage over empty-vector controls in the presence of D/A, confirming their contribution to chemoresistance. This resistance was mediated by evasion of cell cycle arrest in response to chemotherapy, with minimal reductions in apoptosis seen. Given convergence of CDKN2A and CHEK2 pathways on cell cycle G1S transition, we hypothesised that the CDK4/6 inhibitor, palbociclib could enhance efficacy of D/A therapy in AML with deregulation of CDKN2A or CHEK2. Palbociclib induced a rapid G1 arrest in empty vector, CDKN2A- and CHEK2-inactivated cells by 24 hours. Further, it synergised with D/A over longer treatments (4-11 days), demonstrating the therapeutic potential of cell cycle inhibitors in combination with conventional agents to improve chemotherapy response in AML.

Reproductive health care in Catholic-owned hospitals

Mergers that affiliate a hospital with a Catholic owner, network, or system reduce the set of possible reproductive medical procedures since Catholic hospitals have strict prohibitions on contraception. Using changes in ownership of hospitals, we find that Catholic hospitals reduce the per bed rates of tubal ligations by 31%, whereas there is no significant change in related permitted procedures such as Caesarian sections. However, across a variety of measures, we find minimal overall welfare reductions. Still, fewer tubal ligations increase the risk of unintended pregnancies across the United States, imposing a potentially substantial cost for less reliable contraception on women and their partners.

Companion planting with French marigolds protects tomato plants from glasshouse whiteflies through the emission of airborne limonene.

Horticulturalists and gardeners in temperate regions often claim that planting marigolds next to tomato plants protects the tomatoes from the glasshouse whitefly (Trialeurodes vaporariorum Westwood). If shown to hold true, this technique could be used in larger-scale tomato production, protecting the crop and helping to introduce greater plant diversity into these agro-ecosystems. Here we present two large-scale glasshouse trials corresponding to the two main ways growers are likely to use marigolds to control whiteflies. In the first, marigolds are grown next to tomato throughout the growing period and we quantify whitefly population growth from the seedling stage over a 48 day infestation period. Here we show that association with marigolds significantly slows whitefly population development. Introducing additional whitefly-attractive ‘pull’ plants around the perimeter of plots has little effect, but reducing the proportion of marigolds and introducing other non-hosts of whiteflies (basil, nasturtium and Chinese cabbage) also reduces whitefly populations on tomato. The second experiment assesses the efficacy of marigolds when used as an ‘emergency’ measure. Here we allow whitefly populations to build to a high density on unprotected tomatoes then introduce marigolds and assess whitefly population over a further period. Following laboratory work showing limonene to be a major chemical component of French marigolds and a negative behaviour response of whiteflies to this compound, limonene dispensers are added as an additional treatment to this experiment. “Emergency” marigold companion planting yielded minimal reductions in whitefly performance, but the use of limonene dispensers was more effective. Our work indicates that companion planting short vine tomatoes with French marigolds throughout the growing season will slow development of whitefly populations. Introducing marigolds to unprotected tomatoes after significant whitefly build-up will be less effective. The use of limonene dispensers placed near to tomato plants also shows promise. It is argued that this work supports the possibility of the development of a mixture of tomato companion plants that infer ‘associational resistance’ against many major invertebrate pests of tomato. Such a mixture, if comprising edible or ornamental plants, would be economically viable, would reduce the need for additional chemical and biological control, and, if used outdoors, would generate plant-diverse agro-ecosystems that are better able to harbour invertebrate wildlife.

An algorithm for computing the Hilbert–Samuel multiplicities and reductions of zero-dimensional ideals of Cohen–Macaulay local rings

In this paper, we present an algorithm for computing the minimal reductions of m-primary ideals of Cohen–Macaulay local rings. Using this algorithm, we are able to compute the Hilbert–Samuel multiplicities and solve the membership problem for the integral closure of m-primary ideals.

High water recovery and improved thermodynamic efficiency for capacitive deionization using variable flowrate operation

Water recovery is a measure of the amount of treated water produced relative to the total amount of water processed through the system, and is an important performance metric for any desalination method. Conventional operating methods for desalination using capacitive deionization (CDI) have so far limited water recovery to be about 50%. To improve water recovery for CDI, we here introduce a new operating scheme based on a variable (in time) flow rate wherein a low flow rate during discharge is used to produce a brine volume which is significantly less than the volume of diluent produced. We demonstrate experimentally and study systematically this novel variable flowrate operating scheme in the framework of both constant current and constant voltage charge-discharge modes. We show that the variable flowrate operation can increase water recovery for CDI to very high values of ∼90% and can improve thermodynamic efficiency by about 2- to 3-fold compared to conventional constant flowrate operation. Importantly, this is achieved with minimal performance reductions in salt removal, energy consumption, and volume throughput. Our work highlights that water recovery can be readily improved for CDI at very minimal additional cost using simple flow control schemes.

Energy Performance Resilience of UAE Buildings to Climate Change

A large proportion of electricity in the UAE is consumed in meeting air conditioning cooling demands in buildings where up to 80% of a buildings total electricity demand is for cooling. With projected climate changes in the UAE pre­dicting an increase in annual mean temperature of 2.8°C and minimal reductions in relative humidity and global solar radiation by 2050, cooling energy demands are set to increase. This paper reports on a study of how the climatic drivers of cooling energy demand change under a “business-as-usual” scenario of climate change. As annual energy demand for cooling per unit treated area varies across building types, a range of typical UAE commercial and residential buildings are simulated under generated annual hourly projected climate change weather da­tasets of 2020, 2050, and 2080. The results show an increase in cooling demand of 22.2% by 2050 and 40.0% by 2080 and a shift in the sources of these heat gains. The comparative effect of climate changes on the fundamental heat gain paths are examined and discussed to identify the most effective solutions for im­proving energy performance resilience to future climate change in the UAE.

Adaptation, chance, and history in experimental evolution reversals to unicellularity.

Evolution is often deemed irreversible. The evolution of complex traits that require many mutations makes their reversal unlikely. Even in simpler traits, reversals might become less likely as neutral or beneficial mutations, with deleterious effects in the ancestral context, become fixed in the novel background. This is especially true in changes that involve large reorganizations of the organism and its interactions with the environment. The evolution of multicellularity involves the reorganization of previously autonomous cells into a more complex organism; despite the complexity of this change, single cells have repeatedly evolved from multicellular ancestors. These repeated reversals to unicellularity undermine the generality of Dollo's law. In this article, we evaluated the dynamics of reversals to unicellularity from recently evolved multicellular phenotypes of the brewers yeast Saccharomyces cerevisae. Even though multicellularity in this system evolved recently, it involves the evolution of new levels of selection. Strong selective pressures against multicellularity lead to rapid reversibility to single cells in all of our replicate lines, whereas counterselection favoring multicellularity led to minimal reductions to the rates of reversal. History and chance played an important role in the tempo and mode of reversibility, highlighting the interplay of deterministic and stochastic events in evolutionary reversals.

Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1

Spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody–drug conjugates and other targeted delivery approaches. Unfortunately, it is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive. As a result, the design and synthesis of more acid-stable and linker functional group-equipped analogs that retain the low picomolar potency of the parent natural product requires more efficient and step-economical synthetic access. Using uniquely enabling direct complex fragment coupling crotyl- and alkallylsilylation reactions, we report a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is characterized by GI50 values in the low picomolar range, and a proof-of-concept result that the C(15) acetate may be replaced with linker functional group-bearing esters with only minimal reductions in potency.

Recycled glass fiber reinforced polymer composites incorporated in mortar for improved mechanical performance

Glass fiber reinforced polymer (GFRP) panels from retired wind turbines were recycled into discrete structural elements in mortar. Based on 7-day testing, out of Powder, Small, Medium, and Large fiber size groups, the Large group was identified as the optimum size due to the highest modulus of rupture (MR) and toughness index (TI) while maintaining comparable compressive strength (f’c) relative to control. Implementing the Large group at 1, 3, and 5% replacement of sand resulted in 5, 25 and 35% increases in 90-day MR with significant increases in TI and minimal reductions in f’c and no expansion due to alkali-silica reaction.

Alveolar ridge regeneration of damaged extraction sockets using deproteinized porcine versus bovine bone minerals: A randomized clinical trial

BackgroundsClinical benefits in bone grafting of intact extraction socket have been widely known, but limited evidence is available for the procedure in damaged extraction sockets due to periodontal disease.PurposeThis study aimed to determine the dimensional alteration of alveolar ridge following bone grafting of damaged extraction sockets, and compare the outcomes of using deproteinized bovine (DBBM) versus porcine bone mineral (DPBM) in the damaged sockets.Materials and MethodsOne hundred patients (n = 50 for each group) with periodontitis‐induced damaged extraction socket were included in this randomized, single‐blind trial. After removal of tooth and granulation tissue, sites were grafted with either DBBM (DBBM group) or DPBM (DPBM group), and covered with collagen membrane. Linear/volumetric analyses of hard and soft‐tissue dimensions were performed on reconstructed/superimposed computed tomography and scanned cast images, taken immediately and 4 months after surgery.ResultsThe two groups showed comparable hard tissue augmentation with minimal reductions in the grafted volume, as well as in vertical (1.22 ± 2.16 and 1.45 ± 1.92 mm for DPBM and DBBM group, respectively) and horizontal (1.43 ± 3.40 and 1.83 ± 2.85 mm on the central section, respectively) dimensions at 4 months after surgery. However, several cases showed large variations in maintenance of the grafted volume. None of the measured parameters in hard and soft tissue dimensions differed significantly between DBBM and DPBM sites.ConclusionsDBBM and DPBM can comparably augment damaged extraction sockets with minimal postoperative reduction of the grafted volume. However, the large variations in the results should be further evaluated for application in routine dental clinics.

Bayesian Bias Correction of Satellite Rainfall Estimates for Climate Studies

Advances in remote sensing have led to the use of satellite-derived rainfall products to complement the sparse rain gauge data. Although these products are globally and some regional bias corrected, they often show substantial differences relative to ground measurements attributed to local and external factors that require systematic consideration. A decreasing rain gauge network inhibits the continuous validation of these products. Our proposal to deal with this problem was to use a Bayesian approach to merge the existing historical rain gauge information to create consistent satellite rainfall data for long-term applications. Monthly bias correction was applied to Climate Hazards Group Infrared Precipitation with Stations (CHIRPS v2) using a corresponding gridded (0.05°) rain gauge data over East Africa for 33 years (1981–2013). The first 22 years were utilized to derive error fields which were then applied to independent CHIRPS data for 11 years for validation. Assessments of the approach’s influence on the rainfall estimates spatially and temporally were explored. Results showed a significant spatial reduction of the underestimation and overestimation of systematic errors at both monthly and yearly scales. The reduced errors increased with increased rainfall amounts, hence was less so in the relatively drier months. The overall monthly reduction of Root Mean Square Difference (RMSD) was between 4% and 60%, and the Mean Absolute Error (MAE) was between 1% and 63%, while the correlations improved by up to 21%. Yearly, the RMSD was reduced between 17% and 49%, and the MAE between 13% and 48%, while the increase in correlations was between 9% and 17%. Decreased yearly bias correction corresponded with years of high rainfall associated with El Niño. Results for the assessments of the effectiveness of the Bayesian approach showed that it was more effective in reducing systematic errors related to rainfall magnitudes, but its performance decreased in areas of sparse rain gauge network that insufficiently represented rainfall variabilities. This affected areas of deep convection, leading to minimal overestimation reductions associated with the cirrus effect. Conversely, significant corrections were during years of low rainfall from shallow convections. The approach is suitable for long-term applications where consistencies of mean errors can be assumed.

Quantifying the impact of the Great Recession on the AEC industry—a call to reevaluate home office overhead costs

ABSTRACTThe 2007–2009 recession significantly affected the U.S. construction industry, with unemployment peaking at approximately 20%. In such circumstances, construction companies must devise strategies to adapt to and even counteract declining revenue. One tactic is to reduce home office overhead costs, such as bonuses, rent, and business development expenses. The purpose of this study was to examine the degree to which construction companies reduced overhead costs in response to a market downturn, and whether these reductions are correlated with companies’ demographic attributes. A total of 437 contractors across the United States completed a survey on how much their companies reduced expenses; 92% of the respondents reported that their companies reduced overhead in at least one area, by an average of about 15%. Companies with revenue of $100.1 million to $500 million and that primarily performed manufacturing work tended to reduce overhead costs more than other types of construction companies. This study also reveals that larger companies made fewer reductions to overhead, with the exception being roofers who made very minimal reductions regardless of their annual revenue. The Architecture, Engineering, and Construction (AEC) industry can use the data presented in this study to anticipate reductions in overhead spending that future distressed market conditions may necessitate.

Rifampin modulation of xeno- and endobiotic conjugating enzyme mRNA expression and associated microRNAs in human hepatocytes.

Rifampin is a pleiotropic inducer of multiple drug metabolizing enzymes and transporters. This work utilized a global approach to evaluate rifampin effects on conjugating enzyme gene expression with relevance to human xeno‐ and endo‐biotic metabolism. Primary human hepatocytes from 7 subjects were treated with rifampin (10 μmol/L, 24 hours). Standard methods for RNA‐seq library construction, EZBead preparation, and NextGen sequencing were used to measure UDP‐glucuronosyl transferase UGT, sulfonyltransferase SULT, N acetyltransferase NAT, and glutathione‐S‐transferase GST mRNA expression compared to vehicle control (0.01% MeOH). Rifampin‐induced (>1.25‐fold) mRNA expression of 13 clinically important phase II drug metabolizing genes and repressed (>1.25‐fold) the expression of 3 genes (P < .05). Rifampin‐induced miRNA expression changes correlated with mRNA changes and miRNAs were identified that may modulate conjugating enzyme expression. NAT2 gene expression was most strongly repressed (1.3‐fold) by rifampin while UGT1A4 and UGT1A1 genes were most strongly induced (7.9‐ and 4.8‐fold, respectively). Physiologically based pharmacokinetic modeling (PBPK) was used to simulate the clinical consequences of rifampin induction of CYP3A4‐ and UGT1A4‐mediated midazolam metabolism. Simulations evaluating isolated UGT1A4 induction predicted increased midazolam N‐glucuronide exposure (~4‐fold) with minimal reductions in parent midazolam exposure (~10%). Simulations accounting for simultaneous induction of both CYP3A4 and UGT1A4 predicted a ~10‐fold decrease in parent midazolam exposure with only a ~2‐fold decrease in midazolam N‐glucuronide metabolite exposure. These data reveal differential effects of rifampin on the human conjugating enzyme transcriptome and potential associations with miRNAs that form the basis for future mechanistic studies to elucidate the interplay of conjugating enzyme regulatory elements.

Calibration of a Field-Scale Soil and Water Assessment Tool (SWAT) Model with Field Placement of Best Management Practices in Alger Creek, Michigan

Subwatersheds within the Great Lakes “Priority Watersheds” were targeted by the Great Lakes Restoration Initiative (GLRI) to determine the effectiveness of the various best management practices (BMPs) from the U.S. Department of Agriculture-Natural Resources Conservation Service National Conservation Planning (NCP) Database. A Soil and Water Assessment Tool (SWAT) model is created for Alger Creek, a 50 km2 tributary watershed to the Saginaw River in Michigan. Monthly calibration yielded very good Nash–Sutcliffe efficiency (NSE) ratings for flow, sediment, total phosphorus (TP), dissolved reactive phosphorus (DRP), and total nitrogen (TN) (0.90, 0.79, 0.87, 0.88, and 0.77, respectively), and satisfactory NSE rating for nitrate (0.51). Two-year validation results in at least satisfactory NSE ratings for flow, sediment, TP, DRP, and TN (0.83, 0.54, 0.73, 0.53, and 0.60, respectively), and unsatisfactory NSE rating for nitrate (0.28). The model estimates the effect of BMPs at the field and watershed scales. At the field-scale, the most effective single practice at reducing sediment, TP, and DRP is no-tillage followed by cover crops (CC); CC are the most effective single practice at reducing nitrate. The most effective BMP combinations include filter strips, which can have a sizable effect on reducing sediment and phosphorus loads. At the watershed scale, model results indicate current NCP BMPs result in minimal sediment and nutrient reductions (&lt;10%).

Toughening Anhydride-Cured Epoxy Resins Using Fatty Alkyl-Anhydride-Grafted Epoxidized Soybean Oil.

The aim of this work is to develop a series of advanced biobased tougheners for thermosetting epoxy resins suitable for high-performance applications. These bio-rubber (BR) tougheners were prepared via a one-step chemical modification of epoxidized soybean oil using biobased hexanoic anhydride. To investigate their toughening performance, these BR tougheners were blended with diglycidyl ether of bisphenol A epoxy monomers at various weight fractions and cured with anhydride hardeners. Significant improvements in fracture toughness properties, as well as minimal reductions in glass transition temperature (Tg), were observed. When 20 wt % of a BR toughener was utilized, the critical stress intensity factor and critical strain energy release rate of a thermosetting matrix were enhanced by >200 and >500%, respectively, whereas the Tg was reduced by only 20 °C. The phase-separated domains were evenly dispersed across the fracture surfaces as observed through scanning electron microscopy and atomic force microscopy. Moreover, domain sizes were demonstrated to be tunable within the micrometer range by altering the toughener molecular structure and weight fractions. These BR tougheners demonstrate the possibility of achieving toughness while having the thermal properties of standard bisphenol epoxy thermosetting resins.

Agro-morphological characterization of diverse sorghum lines for pre-and post-flowering drought tolerance

The impact of drought stress on sorghum yield does not only depend on the intensity and timing of drought, but as well on the developmental stage of the crop. One of the limitations in breeding for pre-and/or postflowering drought stress resistance in sorghum is the less availability of diverse genetic sources possessing drought tolerant agro-morphological or physiological traits that could be introgressed into elite sorghum lines. This research evaluate a diverse group of 54 introgressed, converted, and commonly used sorghum breeding lines for their tolerance to field drought stress imposed at the pre-flowering and post-anthesis developmental stages in 2015 and 2016 growing seasons. Agro-morphological characteristics such as panicle area, panicle width, and percent green leaf and yield-related characteristics such as total above ground dry biomass and dry panicle weight were identified as significant predictors of grain yield under water stress. The current research identifies other sources that could be use by breeding programs as donor lines for traits related to pre-and postflowering drought tolerance in sorghum. Following statistical distribution and Tukey-Krammer HSD connecting letter tests, lines JB39, SC191, and SC270 and RIL R.11269 were identified as plausible sources for pre-flowering drought tolerance, and JB14, JB15, JB19, JB22, JB24, JB25, JB26, and JB33 as sources for the staygreen trait. While the staygreen is a good selection tool for postflowering drought tolerance, identifying staygreen lines with minimal reductions in grain yield and with earlier flowering dates (JB14, JB22, JB24 and JB25 in this study) than most commonly used staygreen donor lines, will ensure that grain yield is not over sacrificed by the ability of the crop to staygreen under terminal drought conditions.

Self-care support for children and adolescents with long-term conditions: the REfOCUS evidence synthesis

BackgroundSelf-care support (e.g. education, training, peer/professional support) is intended to enhance the self-care capacities of children and young people, while simultaneously reducing the financial burden facing health-care systems.ObjectivesTo determine which models of self-care support for long-term conditions (LTCs) are associated with significant reductions in health utilisation and costs without compromising outcomes for children and young people.DesignSystematic review with meta-analysis.PopulationChildren and young people aged 0–18 years with a long-term physical or mental health condition (e.g. asthma, depression).InterventionSelf-care support in health, social care, educational or community settings.ComparatorUsual care.OutcomesGeneric/health-related quality of life (QoL)/subjective health symptoms and health service utilisation/costs.DesignRandomised/non-randomised trials, controlled before-and-after studies, and interrupted time series designs.Data sourcesMEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, ISI Web of Science, NHS Economic Evaluation Database, The Cochrane Library, Health Technology Assessment database, Paediatric Economic Database Evaluation, IDEAS, reference scanning, targeted author searches and forward citation searching. All databases were searched from inception to March 2015.MethodsWe conducted meta-analyses, simultaneously plotting QoL and health utilisation effects. We conducted subgroup analyses for evidence quality, age, LTC and intervention (setting, target, delivery format, intensity).ResultsNinety-seven studies reporting 114 interventions were included. Thirty-seven studies reported adequate allocation concealment. Fourteen were UK studies. The vast majority of included studies recruited children and young people with asthma (n = 66, 68%). Four per cent of studies evaluated ‘pure’ self-care support (delivered through health technology without additional contact), 23% evaluated facilitated self-care support (≤ 2 hours’/four sessions’ contact), 65% were intensively facilitated (≥ 2 hours’/four sessions’ contact) and 8% were case management (≥ 2 hours’ support with multidisciplinary input). Self-care support was associated with statistically significant, minimal benefits for QoL [effect size (ES) –0.17, 95% confidence interval (CI) –0.23 to –0.11], but lacked clear benefit for hospital admissions (ES –0.05, 95% CI –0.12 to 0.03). This finding endured across intervention intensities and LTCs. Statistically significant, minimal reductions in emergency use were observed (ES –0.11, 95% CI –0.17 to –0.04). The total cost analysis was limited by the small number of data. Subgroup analyses revealed statistically significant, minimal reductions in emergency use for children aged ≤ 13 years (ES –0.10, 95% CI –0.17 to –0.04), children and young people with asthma (ES –0.12, 95% CI –0.18 to –0.06) and children and young people receiving ≥ 2 hours per four sessions of support (ES –0.10, 95% CI –0.17 to –0.03). Preliminary evidence suggested that interventions that include the child or young person, and deliver some content individually, may optimise QoL effects. Face-to-face delivery may help to maximise emergency department effects. Caution is required in interpreting these findings.LimitationsIdentification of optimal models of self-care support is challenged by the size and nature of evidence available. The emphasis on meta-analysis meant that a minority of studies with incomplete but potentially relevant data were excluded.ConclusionsSelf-care support is associated with positive but minimal effects on children and young people’s QoL, and minimal, but potentially important, reductions in emergency use. On current evidence, we cannot reliably conclude that self-care support significantly reduces health-care costs.Future workResearch is needed to explore the short- and longer-term effects of self-care support across a wider range of LTCs.Study registrationThis study is registered as PROSPERO CRD42014015452.FundingThe National Institute for Health Research Health Services and Delivery Research programme.