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Anhedonia – a diminished interest or pleasure in activities – is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development.
Using a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith–Hamilton Pleasure Scale).
Compared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis.
Our findings suggest that anhedonia is a heterogeneous symptom associated with impairments in reward sensitivity and effort-based decision-making.
East of England is considered the “bread basket” of the UK, supplying domestic and global food markets but it is under pressures from policy, economic and environmental challenges. This chapter studies with a mixed-method approach the risks affecting the arable farming sector in the East of England, describing the role of knowledge networks and learning for resilience.
Risk and risk management are essential elements of farming. We show that strategies to cope with risk often go beyond the level of the individual farm. Cooperation, learning and sharing of risks play a vital role in European agriculture. An enabling environment should support cooperative approaches, enable a diversity of risk management solutions and harness novel technological opportunities.
Portable oxygen concentrators (POCs) are medical devices that use physical means to separate oxygen from the atmosphere to produce concentrated, medical-grade gas. Providing oxygen to low-resources environments, such as austere locations, military combat zones, rural Emergency Medical Services (EMS), and during disasters, becomes expensive and logistically intensive. Recent advances in separation technology have promoted the development of POC systems ruggedized for austere use. This review provides a comprehensive summary of the available data regarding POCs in these challenge environments.
PubMed, Google Scholar, and the Defense Technical Information Center were searched from inception to November 2021. Articles addressing the use of POCs in low-resource settings were selected. Three authors were independently involved in the search, review, and synthesis of the articles. Evidence was graded using Oxford Centre for Evidence-Based Medicine guidelines.
The initial search identified 349 articles, of which 40 articles were included in the review. A total of 724 study subjects were associated with the included articles. There were no Level I systematic reviews or randomized controlled trials.
Generally, POCs are a low-cost, light-weight tool that may fill gaps in austere, military, veterinary, EMS, and disaster medicine. They are cost-effective in low-resource areas, such as rural and high-altitude hospitals in developing nations, despite relatively high capital costs associated with initial equipment purchase. Implementation of POC in low-resource locations is limited primarily on access to electricity but can otherwise operate for thousands of hours without maintenance. They provide a unique advantage in combat operations as there is no risk of explosive if oxygen tanks are struck by high-velocity projectiles. Despite their deployment throughout the battlespace, there were no manuscripts identified during the review involving the efficacy of POCs for combat casualties or clinical outcomes in combat. Veterinary medicine and animal studies have provided the most robust data on the physiological effectiveness of POCs. The success of POCs during the coronavirus disease 2019 (COVID-19) pandemic highlights the potential for POCs during future mass-casualty events. There is emerging technology available that combines a larger oxygen concentrator with a compressor system capable of refilling small oxygen cylinders, which could transform the delivery of oxygen in austere environments if ruggedized and miniaturized. Future clinical research is needed to quantify the clinical efficacy of POCs in low-resource settings.
Resource-intensive interventions and education are susceptible to a lack of long-term sustainability and regression to the mean. The respiratory culture nudge changed reporting to “Commensal Respiratory Flora only: No S. aureus/MRSA or P. aeruginosa.” This study demonstrated sustained reduction in broad-spectrum antibiotic duration and long-term sustainability 3 years after implementation.
The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.
Intrauterine preeclampsia exposure affects the lifelong cardiometabolic health of the child. Our study aimed to compare the growth (from birth to 6 months) of infants exposed to either a normotensive pregnancy or preeclampsia and explore the influence of being born small for gestational age (SGA). Participants were children of women participating in the Post-partum, Physiology, Psychology and Paediatric follow-up cohort study. Birth and 6-month weight and length z-scores were calculated for term and preterm (<37 weeks) babies, and change in weight z-score, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-score were calculated. Compared with normotensive exposed infants (n = 298), preeclampsia exposed infants (n = 84) were more likely to be born SGA (7% versus 23%; P < 0.001), but weight gain from birth to 6 months, by any measure, did not differ between groups. Infants born SGA, irrespective of pregnancy exposure, were more likely to have rapid weight gain and had greater increases in weight z-score compared with those not born SGA. Preeclampsia exposed infants born SGA may benefit from interventions designed to prevent future cardiometabolic disease.
Approved treatments for bipolar depression are limited and associated with a spectrum of undesirable side effects. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. Lumateperone is currently being investigated for the treatment of bipolar depression (major depressive episodes [MDE] associated with bipolar I and bipolar II disorder). This Phase 3 randomized, double-blind, parallel-group, placebo-controlled multinational study (NCT03249376) investigated the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a MDE.
Patients (18 75 years) with a clinical diagnosis of bipolar I or bipolar II disorder who were experiencing a MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score =20 and a Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score =4 at screening and baseline) were randomized to lumateperone 42mg or placebo for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to Day 43 in MADRS total score and CGI-BP-S scores, respectively. Secondary efficacy outcomes included response (MADRS improvement = 50%) and remission (MADRS total score =12) at Day 43. Safety assessments included treatment emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms (EPS), and suicidality.
In this study, 377 patients received treatment (placebo, n=189; lumateperone 42mg, n=188) and 333 completed treatment. Patients in the lumateperone 42-mg group had significantly greater mean improvement on MADRS total score change from baseline to Day 43 compared with placebo (least squares mean difference [LSMD]=-4.6; 95% confidence interval [CI]=-6.34, −2.83; effect size vs placebo [ES]=-0.56; P<.0001). Lumateperone treatment was associated with significant MADRS improvement in both patients with bipolar I (LSMD=-4.0; 95% CI=-5.92, −1.99; ES=-0.49; P<.0001) and bipolar II (LSMD=-7.0; 95% CI=-10.92, −3.16; ES=-0.81; P=.0004). The lumateperone 42-mg group also had significantly greater mean improvement in CGI-BP-S total score compared with placebo (LSMD=-0.9; 95% CI=-1.37, −0.51; ES=-0.46; P<.001). Lumateperone compared with placebo had significantly greater MADRS response rate (51.1% vs 36.7%; odds ratio=2.98; P<.001) and remission rates (P=.02) at Day 43. Lumateperone treatment was well tolerated, with minimal risk of EPS, metabolic, and prolactin side effects.
Lumateperone 42 mg significantly improved depression symptoms in both patients with bipolar I and bipolar II depression. Lumateperone was generally well tolerated. These results suggest that lumateperone 42 mg may be a promising new treatment for bipolar depression associated with bipolar I or bipolar II disorder.
Current treatments for schizophrenia are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides =150mg/dL, high density lipoprotein cholesterol (HDL) <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) =130mmHg or diastolic BP =85mmHg, fasting glucose =100mg/dL. Patients with MetSy have an elevated risk of developing type II diabetes and increased mortality due to cardiovascular disease. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA approved for the treatment of schizophrenia. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials. This post hoc analysis of 2 randomized, double-blind, placebo-controlled studies of patients with an acute exacerbation of schizophrenia compared rates of MetSy with lumateperone and risperidone. Data from an open-label long-term trial of lumateperone were also evaluated.
The incidence and shift in MetSy were analyzed in data pooled from 2 short-term (4 or 6 week) placebo- and active-controlled (risperidone 4mg) studies of lumateperone 42mg (Studies 005 and 302). The pooled lumateperone data were compared with data for risperidone. Data from an open-label 1-year trial (Study 303) evaluated MetSy in patients with stable schizophrenia switched from prior antipsychotic (PA) treatment to lumateperone 42mg.
In the acute studies (n=256 lumateperone 42mg, n=255 risperidone 4mg), rates of MetSy were similar between groups at baseline (16% lumateperone, 19% risperidone). At the end of treatment (EOT), MetSy was less common with lumateperone than with risperidone (13% vs 25%). More lumateperone patients (46%) compared with risperidone (25%) patients improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. Conversely, more patients on risperidone than on lumateperone developed MetSy during treatment (13% vs 5%). Differences in MetSy conversion rates were driven by changes in triglycerides and glucose. In the long-term study (n=602 lumateperone 42mg), 33% of patients had MetSy at PA baseline. Thirty-six percent of patients (36%) with MetSy at PA baseline improved to no longer meeting criteria at EOT. Fewer than half that percentage shifted from not meeting MetSy criteria to having MetSy (15%).
In this post hoc analysis, lumateperone 42mg patients had reduced rates of MetSy compared with risperidone patients. In the long-term study, patients with MetSy on PA switched to lumateperone 42mg had a reduction in the risk of MetSy. These results suggest that lumateperone 42mg is a promising new treatment for schizophrenia with a favorable metabolic profile.
Froth flotation by small air bubbles has been traditionally used in industry to capture fine minerals and other hydrophobic particles. This method, however, is not efficient for capturing very small particles. The present work is motivated by a new agglomeration process that overcomes this lack of efficiency. It consists of mixing a particle suspension and saltwater-filled droplets covered with semi-permeable oil layers. This paper investigates the two-particle dynamics of a solid particle and a semi-permeable spherical drop that expands due to osmosis in an external, pure extensional flow field. A dimensionless engulfment parameter measures the relative effects of droplet growth and convective flow. The computational results from numerical integration determine a transient collision efficiency, which describes the influence of hydrodynamic interactions and osmotic flow on particle capture. The results show that drop expansion, which decays slowly with time, greatly increases particle capture rates, especially for small particles. Moreover, as the engulfment parameter increases, there is a transition from flow-dominated capture to expansion-dominated capture. For the case of a non-expanding droplet, we provide a numerical solution for the transient pair distribution function, which enables us to explain the transient particle-capture rate in terms of the microstructure of the suspension. Furthermore, we derive an analytical expression for the initial collision efficiency at zero times, which agrees with our numerical data. The numerical results for non-expanding droplets at long times show increasing collision efficiency as the permeability increases and when the size ratio is near unity, in agreement with previous steady-state calculations.
The importance of data science in society today is undeniable, and now is the time to prepare data science talent (National Academies of Sciences, Engineering, and Medicine 2018). Data science demands collaboration, but collaboration within political science departments has been weak in teaching data science. Bridging substantive and methods courses can critically aid in teaching data science because it facilitates this collaboration. Our innovation is to integrate data science into both substantive and methods courses through a dedicated data science course and modules on data science topics taught in substantive courses. This approach allows not only for more opportunities for teaching and practice of data science methods but also helps students to understand how social, economic, and political biases and incentives can affect their data.
A fully three-dimensional boundary-integral method (BIM) is developed for the interaction of drops, suspended in a uniform far-field flow at small Reynolds number, with arbitrary Lyapunov surfaces. The close approach of fluid interfaces to solid surfaces poses significant challenges for numerical BIM implementations, due to the highly singular behaviour of single- and double-layer boundary integrals. Two new methods are described that generalize the accurate calculation of the highly singular surface integrals used by high-order desingularization techniques. The first method is semi-analytical, and applies to axisymmetric solid obstacles (in an arbitrary three-dimensional configuration). An axisymmetric particle can be divided into a series of characteristic disks along its axis, for which closed-form expressions for single and double layers are derived in terms of elliptic integrals. To accommodate arbitrary smooth surfaces, a multimesh desingularization method is introduced that calculates surface integrals utilizing a hierarchy of embedded mesh resolutions, together with distance-activated mesh interactions. Several particle shapes, including spherocylinders (capsules) and flat plates, are used to represent major classes characteristic of porous media. A droplet approaching a capsule will break up after forming two lobes, connected by a thin filament, on either side of the capsule. The cross-sectional shape of the filament affects lubrication behaviour. A constriction made of two parallel capsules, even of low aspect ratio, significantly retards drop passage compared to two spheres. Trends in drop squeezing between two capsules are summarized over a range of capillary number, viscosity ratio, drop size and capsule length. A constriction of two coplanar plates results in notably different lubrication and squeezing behaviour. Flow rectification is demonstrated for constrictions that are non-symmetrical with respect to flow reversal, for several non-axisymmetric particles.
In this article, we present the results of an analysis of variation, whose main objectives are to ascertain the ethnocultural identities speakers declare and to measure the impact of internal, external and identity factors on the use of the connectors of consequence (ça) fait que vs donc vs alors vs so. Our research emphasizes that while there is no consensus as to the terminology chosen to express these identities, it is important to consider ethnocultural identities as a complementary factor conditioning linguistic variation. It also demonstrates that for communities whose linguistic practices and norms straddle those of minority- and majority-French language communities, the minority/majority dichotomy needs to be nuanced, according to the social and ethnocultural identity dynamics that may characterize specific communities.
Engagement of frontline staff, along with senior leadership, in competition-style healthcare-associated infection reduction efforts, combined with electronic clinical decision support tools, appeared to reduce antibiotic regimen initiations for urinary tract infections (P = .01). Mean monthly standardized infection and device utilization ratios also decreased (P < .003 and P < .0001, respectively).
Archaeologists have struggled to combine remotely sensed datasets with preexisting information for landscape-level analyses. In the American Southeast, for example, analyses of lidar data using automated feature extraction algorithms have led to the identification of over 40 potential new pre-European-contact Native American shell ring deposits in Beaufort County, South Carolina. Such datasets are vital for understanding settlement distributions, yet a comprehensive assessment requires remotely sensed and previously surveyed archaeological data. Here, we use legacy data and airborne lidar-derived information to conduct a series of point pattern analyses using spatial models that we designed to assess the factors that best explain the location of shell rings. The results reveal that ring deposit locations are highly clustered and best explained through a combination of environmental conditions such as distance to water and elevation as well as social factors.
Invasive predators have decimated island biodiversity worldwide. Rats (Rattus spp.) are perhaps the greatest conservation threat to island fauna. The ground nesting Palau Micronesian Scrubfowl Megapodius laperouse senex (Megapodiidae) inhabits many of the islands of Palau’s Rock Island Southern Lagoon Conservation Area (RISL) in the western Pacific. These islands are also heavily visited by tourists and support populations of introduced rats, both of which may act as added stressors for the scrubfowl. Using passive chew-tag and call playback surveys on five tourist-visited and five tourist-free islands, we investigated if rats and tourists negatively affect scrubfowl, and if higher rat activity is associated with tourist presence. Rat detection probability and site occupancy were significantly higher on tourist visited (89% and 99%, respectively) compared to tourist-free islands (52% and 73%). Scrubfowl were detected at significantly more stations on tourist-free (93%) than tourist visited (47%) islands and their relative abundance was higher (2.66 and 1.58 birds per station, respectively), although not statistically significantly. While rat occupancy probability likewise had a non-significant negative effect on scrubfowl numbers across islands, our results show a negative relationship between tourist presence and scrubfowl in the RISL. Our findings also suggest that rat populations may be augmented by tourist visitation in the RISL. Although this situation may not seriously affect the scrubfowl, it may be highly detrimental to populations of other threatened island landbirds.
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.
Lumateperone (lumateperone tosylate, ITI-007) is an investigational drug for the treatment of schizophrenia, bipolar depression, and other disorders. Lumateperone has a unique mechanism of action that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This may provide advantages in the treatment of the broad symptoms associated with schizophrenia, including negative and depression symptoms. In 2 previous placebo-controlled trials in patients with acute schizophrenia, lumateperone 42mg (ITI-007 60mg) demonstrated statistically significant improvement in the Positive and Negative Syndrome Scale (PANSS) Total score compared with placebo. In these studies, lumateperone was well tolerated with a safety profile similar to placebo. This open-label long-term study evaluated the safety and effectiveness of lumateperone 42mg in patients with schizophrenia and stable symptoms.
Patients with stable schizophrenia were treated for up to 1 year with lumateperone 42mg. Safety assessments included adverse events (AEs), body weight, laboratory parameters, and extrapyramidal symptoms (EPS)/motor symptom assessments. Efficacy analyses included evaluation of changes in PANSS Total score and in depression symptoms, as measured by the Calgary Depression Scale for Schizophrenia (CDSS).
In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42mg; at the time of this interim analysis, 107 patients had completed 1 year of treatment. Only 4 TEAEs occurred in ≥5% of patients (weight decrease, dry mouth, headache and diarrhea); the majority of AEs were mild or moderate in intensity. Most metabolic parameters and mean prolactin levels decreased from SOC baseline, as did mean body weight and BMI. Based on AE reporting and EPS/motor symptom scales, lumateperone treatment was associated with minimal EPS risk. Lumateperone 42mg treatment was associated with significant reductions in PANSS Total score from baseline, with continuing PANSS improvement throughout the study. In patients with moderate-to-severe depression symptoms at baseline (CDSS>5), mean CDSS scores decreased from 7.4 (baseline) to 3.1 (Day 300); 60% of patients met CDSS response criteria (50% improvement from baseline) by Day 75 and this response rate was maintained through day 300. Similar magnitude of CDSS improvement was seen regardless of concurrent antidepressant therapy.
In long-term treatment, lumateperone was associated with minimal metabolic, EPS, and cardiovascular safety issues relative to current SOC antipsychotic therapy. Lumateperone improved schizophrenia symptoms with continued long-term treatment. In patients with moderate-to-severe depression symptoms at baseline, lumateperone treatment was associated with marked improvement in CDSS scores. These data are consistent with and extend data previously reported in placebo-controlled studies in patients with acute schizophrenia treated with lumateperone.
Supported by funding from Intra-Cellular Therapies, Inc.
Lumateperone (ITI-007) is in late-phase clinical development for schizophrenia. Lumateperone has a unique mechanism of action that modulates serotonin, dopamine, and glutamate neurotransmission. This pooled analysis of lumateperone in 3 randomized, double-blind, placebo-controlled studies was conducted to evaluate the safety and tolerability of lumateperone 42mg (ITI-007 60mg).
Data were pooled from the 3 controlled late-phase studies of lumateperone 42mg in patients with acute exacerbation of schizophrenia. Safety assessments of all patients who received at least one dose of any treatment included treatment-emergent adverse events (TEAEs), changes in laboratory parameters, extrapyramidal symptoms (EPS), and vital signs.
The safety population comprised 1,073 patients (placebo [n=412], lumateperone 42mg [n=406], risperidone [n=255]). TEAEs that occurred in the lumateperone 42mg group at a rate of ≥5% and twice placebo were somnolence/sedation (24.1% vs 10.0%) and dry mouth (5.9% vs 2.2%). Rates of discontinuation due to TEAEs with lumateperone 42mg (0.5%) were similar to placebo (0.5%) and lower than risperidone (4.7%). Mean change in weight and rates of EPS-related TEAEs were less for lumateperone 42mg and placebo patients than risperidone patients. Mean change from baseline in metabolic parameters were similar or smaller for lumateperone 42mg vs placebo. Mean changes were notably higher in risperidone patients vs lumateperone 42mg and placebo for glucose, cholesterol, triglycerides, and prolactin.
In this pooled analysis, lumateperone 42mg showed good tolerability with potential benefits over risperidone for metabolic, prolactin, and EPS risks. The only TEAE that occurred in >10% of lumateperone patients was somnolence/sedation, which was impacted by morning administration; in subsequent studies that administered lumateperone in the evening, somnolence/sedation rates were markedly reduced. These results suggest that lumateperone 42mg may be a promising new treatment for schizophrenia.
Supported by funding from Intra-Cellular Therapies, Inc.
Home care for older people in England is commissioned through local authorities working predominantly with independent providers of care. Commissioners operate in a market model, planning and procuring home care services for local populations. Their role involves ‘managing’ and ‘shaping’ the market to ensure an adequate supply of care providers. Another imperative, emerging from the principles of personalisation, is the drive to achieve user outcomes rather than ‘time and task’ objectives. Little formal research has investigated the way commissioners reconcile these different requirements and organise commissioning. This study investigated commissioning approaches using qualitative telephone interviews with ten commissioners from different local authorities in England. The characteristics of commissioning were analysed thematically. Findings indicated (a) commissioning involved complex systems and processes, uniquely shaped for the local context, but frequently changed, suggesting a constant need for reframing commissioning arrangements; (b) partnerships with providers were mainly transactional, with occasional examples of collaborative models, that were considered to facilitate flexible services more appropriate for commissioning for personalised outcomes; and (c) only a small number of commissioners had attempted to reconcile the competing and incompatible goals of tightly prescribed contracting and working collaboratively with providers. A better understanding of flexible contracting arrangements and the hallmarks of a trusting collaboration is required to move beyond the procedural elements of contracting and commissioning.