We present a simple, automated method for high-throughput formation of droplet interface bilayers (DIBs) in a microfluidic device. We can form complex DIB networks that are able to fill predefined ...three dimensional architectures. Moreover, we demonstrate the flexibility of the system by using a variety of lipids including 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).
Summary
What is known and objectives
About half of all patients taking antihypertensives discontinue treatment by 12 months. There is potential for substantial health gains at both individual and ...population levels through improved treatment adherence. The objective was to evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure (BP) control.
Methods
Design: prospective, non‐blinded, cluster‐randomized, controlled trial.
Participants: adults with primary hypertension who obtained antihypertensives in the previous 6 months. Patients with poor refill adherence were preferentially identified with the help of a purpose‐built software application.
Intervention: package comprising BP monitor; training on BP self‐monitoring; motivational interviewing; medication use review; prescription refill reminders.
Follow‐up: six months.
Primary outcome: change in proportion self‐reporting medication adherence.
Secondary outcome: BP changes.
Results
Participants (n = 395; intervention – 207; control – 188) had a mean age of 66.7 years; 51.1% were males. The proportion of adherent participants increased in both groups but was not significantly different between groups 57·2% to 63·6% (control) vs. 60·0% to 73·5% (intervention), P = 0·23. The mean reduction in systolic BP was significantly greater in the intervention group (10·0 mmHg vs. 4·6 mmHg; P = 0·05). The proportion of patients who were non‐adherent at baseline and adherent at 6 months was 22·6% (95%CI 5·1–40·0%) higher in the intervention group (61·8% vs. 39·2%, P = 0·007). Among participants with baseline BP above target, reduction of systolic BP was significantly greater in the intervention group by 7·2 mmHg (95%CI 1·6–12·8 mmHg); (P = 0·01). Among participants non‐adherent at baseline and above target BP, the proportion reporting adherence at 6 months was significantly greater in the intervention group 56·8% vs. 35·9%, P = 0·039).
What is new and conclusion
This community pharmacist intervention resulted in improved adherence to antihypertensive medication and reduced systolic BP.
To evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure (BP) control. This community pharmacist intervention resulted in improved adherence to antihypertensive medication and reduced systolic BP.
The JET neutral beam injection (NBI) system is undergoing an upgrade of both beam power and pulse duration, which will be completed in 2011. In order to obtain an early assessment of the performance ...of the upgraded injectors, two positive ion neutral injectors (PINIs) with modified ion source and accelerator configuration were installed on Octant 8 Neutral Injector Box and successfully commissioned in summer 2009. Both PINIs were routinely delivering ∼2
MW of deuterium neutral beam power during the JET experimental campaign in autumn 2009. These early tests allowed us to predict with confidence that the JET NBI upgrade objective of injecting 34
MW of total deuterium neutral beam power into the JET plasma will be achieved.
The preparation of an Investigational Medicinal Product Dossier (IMPD) for a radiopharmaceutical to be used in a clinical trial is a challenging proposition for radiopharmaceutical scientists working ...in small-scale radiopharmacies. In addition to the vast quantity of information to be assembled, the structure of a standard IMPD is not well suited to the special characteristics of radiopharmaceuticals. This guideline aims to take radiopharmaceutical scientists through the practicalities of preparing an IMPD, in particular giving advice where the standard format is not suitable. Examples of generic IMPDs for three classes of radiopharmaceuticals are given: a small molecule, a kit-based diagnostic test and a therapeutic radiopharmaceutical.
An efficient two-step, one-pot, biotransformation involving the fluorinase enzyme is described for the synthesis of 5-deoxy-5-(18)Ffluororibose, a novel (18)F-fluorinated sugar suitable for positron ...emission tomography (PET) applications.
Summary Background Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of ...combination nivolumab plus ipilimumab as first-line therapy for NSCLC. Methods The open-label, phase 1, multicohort study (CheckMate 012) cohorts reported here were enrolled at eight US academic centres. Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV, chemotherapy-naive NSCLC. Patients were randomly assigned (1:1:1) by an interactive voice response system to receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks, or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression, unacceptable toxicities, or withdrawal of consent. Data from the latter two cohorts, which were considered potentially suitable for further clinical development, are presented in this report; data from the other cohort (as well as several earlier cohorts) are described in the appendix . The primary outcome was safety and tolerability, assessed in all treated patients. This ongoing study is registered with ClinicalTrials.gov , number NCT01454102. Findings Between May 15, 2014, and March 25, 2015, 78 patients were randomly assigned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks (n=38) or nivolumab every 2 weeks plus ipilimumab every 6 weeks (n=40). One patient in the ipilimumab every-6-weeks cohort was excluded before treatment; therefore 77 patients actually received treatment (38 in the ipilimumab every-12-weeks cohort; 39 in the ipilimumab every-6-weeks cohort). At data cut-off on Jan 7, 2016, 29 (76%) patients in the ipilimumab every-12-weeks cohort and 32 (82%) in the ipilimumab every-6-weeks cohort had discontinued treatment. Grade 3–4 treatment-related adverse events occurred in 14 (37%) patients in the ipilimumab every-12-weeks cohort and 13 (33%) patients in the every-6-weeks cohort; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase (three 8% and no patients), pneumonitis (two 5% and one 3% patients), adrenal insufficiency (one 3% and two 5% patients), and colitis (one 3% and two 5% patients). Treatment-related serious adverse events were reported in 12 (32%) patients in the ipilimumab every-12-weeks cohort and 11 (28%) patients in the every-6-weeks cohort. Treatment-related adverse events (any grade) prompted treatment discontinuation in four (11%) patients in the every-12-weeks cohort and five (13%) patients in the every-6-weeks cohort. No treatment-related deaths occurred. Confirmed objective responses were achieved in 18 (47% 95% CI 31–64) patients in the ipilimumab every-12-weeks cohort and 15 (38% 95% CI 23–55) patients in the ipilimumab every-6-weeks cohort; median duration of response was not reached in either cohort, with median follow-up times of 12·8 months (IQR 9·3–15·5) in the ipilimumab every-12-weeks cohort and 11·8 months (6·7–15·9) in the ipilimumab every-6-weeks cohort. In patients with PD-L1 of 1% or greater, confirmed objective responses were achieved in 12 (57%) of 21 patients in the ipilimumab every-12-weeks cohort and 13 (57%) of 23 patients in the ipilimumab every-6-weeks cohort. Interpretation In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response. To our knowledge, the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC, supporting further assessment of this combination in a phase 3 study. Funding Bristol-Myers Squibb.
•The ABCD Study® is an open-science, multi-site, prospective study following over 11,800 9- and 10-year-old youth into early adulthood.•At baseline, the majority of the ABCD Study youth reported ...recently using caffeine (67.6 %) and 22.5 % reported sipping alcohol.•The ABCD Study cohort reported little to no use of drugs of abuse (<1% for any drug category) at baseline.•Total caffeine use and early alcohol sipping were linked with demographic variables, externalizing behaviors, and parental history of AUD.•Aside from caffeine use and early alcohol sipping, the baseline ABCD Study cohort can be considered relatively substance-naïve.
The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12.
This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort’s early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD).
At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p’s<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03).
ABCD Study participants aged 9–10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.
Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved ...by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization
. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
Much postpartum physical and psychological morbidity is not addressed by present care, which tends to focus on routine examinations. We undertook a cluster randomised controlled trial to assess ...community postnatal care that has been redesigned to identify and manage individual needs.
We randomly allocated 36 general practice clusters from the West Midlands health region of the UK to intervention (n=17) or control (19) care. Midwives from the practices recruited women and provided care. 1087 (53%) of 2064 women were in practices randomly assigned to the intervention group, with 977 (47%) women in practices assigned to the control group. Care was led by midwives, with no routine contact with general practitioners, and was extended to 3 months. Midwives used symptom checklists and the Edinburgh postnatal depression scale (EPDS) to identify health needs and guidelines for the management of these needs. Primary outcomes at 4 months were obtained by postal questionnaire and included the women's short form 36 physical (PCS) and mental (MCS) component summary scores and the EPDS. Secondary outcomes were women's views about care. Multilevel analysis accounted for possible cluster effects.
801 (77%) of 1087 women in the intervention group and 702 (76%) of 977 controls responded at 4 months. Women's mental health measures were significantly better in the intervention group (MCS, 3·03 95% CI 1·53–4·52; EPDS −1·92 −2·55 to −1·29; EPDS 13+ odds ratio 0·57 0·43–0·76) than in controls, but the physical health score did not differ.
Redesign of care so that it is midwife-led, flexible, and tailored to needs, could help to improve women's mental health and reduce probable depression at 4 months' postpartum.
![From [11C]CO2 to [11C]amide...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1364-548X_1359-7345/small "From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu reaction")
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