Carbon monoxide (CO) is both a substance hazardous to health and a side product of a number of industrial processes, such as methanol steam reforming and large-scale oxidation reactions. The separation of CO from nitrogen (N2) in industrial processes is considered to be difficult because of the similarities of their electronic structures, sizes, and physicochemical properties (e.g., boiling points). Carbon monoxide is also a major poison in fuel cells because of its adsorption onto the active sites of the catalysts. It is therefore of the utmost economic importance to discover new materials that enable effective CO capture and release under mild conditions. However, methods to specifically absorb and easily release CO in the presence of contaminants, such as water, nitrogen, carbon dioxide, and oxygen, at ambient temperature are not available. Here, we report the simple and versatile fabrication of a new class of hybrid materials that allows capture and release of carbon monoxide under mild conditions. We found that carborane-containing metal complexes encapsulated in networks made of poly(dimethylsiloxane) react with CO, even when immersed in water, leading to dramatic color and infrared signature changes. Furthermore, we found that the CO can be easily released from the materials by simply dipping the networks into an organic solvent for less than 1 min, at ambient temperature and pressure, which not only offers a straightforward recycling method, but also a new method for the “on-demand” release of carbon monoxide. We illustrated the utilization of the on-demand release of CO from the networks by carrying out a carbonylation reaction on an electron-deficient metal complex that led to the formation of the CO-adduct, with concomitant recycling of the gel. We anticipate that our sponge-like materials and scalable methodology will open up new avenues for the storage, transport, and controlled release of CO, the silent killer and a major industrial poison.

The aldo-keto reductase 1C3 (AKR1C3) isoform plays a vital role in the biosynthesis of androgens and is considered an attractive target in prostate cancer (PCa). No AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid and indomethacine are non-steroidal anti-inflammatory drugs known to inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. Recently, we employed a scaffold hopping approach to design a new class of potent and selective AKR1C3 inhibitors based on a N-substituted hydroxylated triazole pharmacophore. Following a similar strategy, we designed a new series focused around an acidic hydroxybenzoisoxazole moiety, which was rationalised to mimic the benzoic acid role in the flufenamic scaffold. Through iterative rounds of drug design, synthesis and biological evaluation, several compounds were discovered to target AKR1C3 in a selective manner. The most promising compound of series (6) was found to be highly selective (up to 450-fold) for AKR1C3 over the 1C2 isoform with minimal COX1 and COX2 off-target effects. Other inhibitors were obtained modulating the best example of hydroxylated triazoles we previously presented. In cell-based assays, the most promising compounds of both series reduced the cell proliferation, prostate specific antigen (PSA) and testosterone production in AKR1C3-expressing 22RV1 prostate cancer cells and showed synergistic effect when assayed in combination with abiraterone and enzalutamide. Structure determination of AKR1C3 co-crystallized with one representative compound from each of the two series clearly identified both compounds in the androstenedione binding site, hence supporting the biochemical data.

One-pot reaction between 8-hydroxyquinoline-2-carboxaldehyde (HQC) and tris(hydroxymethyl)aminomethane (TRIS) followed by in situ cyclization yielded an oxazolidine based ligand which produced four mononuclear complexes of MnII(1), CoII(2), NiII(3), ZnII(4), a tetranuclear iron (FeIII4) complex (5) and a trinuclear cobalt (CoIICoIII2) complex (6). Magnetic studies show dominant antiferromagnetic interaction in tetranuclear iron (FeIII4) complex 5 and presence of the slow relaxation of magnetisation in 6. The compounds were also studied for their antibacterial properties. The oxazolidine ligand (H3L2) of this study showed good antimicrobial activity not only against Gram-positive bacteria but against Gram-negative bacteria too. The antimicrobial efficacy of the metal complexes (1–6) is also reported.

Semiconductor nanostructures like CdSe quantum dots and colloidal nanoplatelets exhibit remarkable optical properties, making them interesting for applications in optoelectronics and photocatalysis. For both areas of application a detailed understanding of the electronic structure is essential to achieve highly efficient devices. The electronic structure can be probed using the fact that optical properties of semiconductor nanoparticles are found to be extremely sensitive to the presence of excess charges that can for instance be generated by means of an electrochemical charge transfer via an electrode. Here we present the use of potential modulated absorption spectroscopy (EMAS) as a versatile spectroelectrochemical method to obtain absolute band edge positions of CdSe nanostructures versus a well-defined reference electrode under ambient conditions. In this the spectral properties of the nanoparticles are monitored dependent on an applied electrochemical potential. We developed a bleaching model that yields the lowest electronic state in the conduction band of the nanostructures. A change in the band edge positions caused by quantum confinement is shown both for CdSe quantum dots as well as for colloidal nanoplatelets. In the case of CdSe quantum dots these findings are in good agreement with tight binding calculations. The method presented is not limited to CdSe nanostructures but can be used as a universal tool. Hence, this technique allows the determination of absolute band edge positions of a large variety of materials used in various applications.

Introduction: There are risks to the safety of medicines management when patient care is transferred between healthcare organisations, for example when a patient is discharged from hospital. Using the theoretical concept of resilience in healthcare, this study aimed to better understand the proactive role that patients can play in creating a safer, resilient medicines management at a common transition of care. Methods: Qualitative interviews with 60 cardiology patients six weeks after their discharge from two UK hospitals explored patients’ experiences with their discharge medicines. Data were initially subjected to an inductive thematic analysis and a subsequent theory-guided deductive analysis. Results: During interviews twenty-three patients described medicines management resilience strategies in two main themes: identifying system vulnerabilities; and establishing self-management strategies. Patients could anticipate problems in the system that supplied them with medicines and took specific actions to prevent them. They also identified when errors had occurred both before and after medicines had been supplied and took corrective action to avoid harm. Some reported how they had not foreseen problems or experienced patient safety incidents. Patients recounted how they ensured information about medicines changes was correctly communicated and acted upon, and identified their strategies to enhance their own reliability in adherence and resource management. Conclusion: Patients experience the impact of vulnerabilities in the medicines management system across the secondary-primary care transition but many are able to enhance system resilience through developing strategies to reduce the risk of medicines errors occurring. Consequently, there are opportunities – with caveats – to elicit, develop and formalise patients’ capabilities which would contribute to safer patient care and more effective medicines management.

Introduction As a consequence of the low cost and perceived safety, proton pump inhibitors (PPIs) are widely prescribed but they can cause longterm adverse effects and are often overprescribed. For most patients PPIs should not be continued long-term as patients can become dependent on PPIs and they are rarely stepped down/off treatment. We aimed to measure whether a dyspepsia review service could help patients on PPIs to step down/off treatment whilst still keeping them symptom free. Methods Pharmacists were provided with training on dyspepsia management. Four general practices were selected. Patients taking a PPI for more than two months were included. A list of exclusion criteria (e.g. active ulcers, newly initiated) was applied. Between six and eight dyspepsia review clinics were run at each site. Patients were booked into a 15-minute consultation. A concordance style consultation was held with clinicians providing information on dyspepsia management and exploring the patients’ ideas, concerns and expectations about stepping down or stepping off treatment. A follow-up audit was performed at four months to determine if patients had remained stepped down/off. An economic evaluation of clinic costs and drugs savings was performed. Results A total of 508 patients were invited to a review; 136 did not attend and 58 were excluded due to not meeting the inclusion criteria, leaving 314 patients reviewed for step-down/step-off. Successful step down/step off was achieved in 257 people (82% of those reviewed). The total cost savings of PPIs was £7,100. The additional cost of alginates was £1,207 giving a net saving on medicines of £5,893 per annum. Set-up costs were £1,194 and staff costs £3,524 to £5,156 giving total running costs, which vary dependent on the Agenda for Change (AfC) grade of pharmacist involved, of £4,720 - £6,351. Conclusion A dyspepsia review clinic is cost-neutral to run but, given that many patients are on polypharmacy, PPI step down might best be considered as part of a holistic medication review clinic.

As the Fourth Review Conference of the Chemical Weapons Convention meets next month, state parties need to address mounting concerns about the potential development and use of law-enforcement weapons involving chemical agents that act on the central nervous system (CNS).

Since 2010 the Stonehenge Hidden Landscapes Project (SHLP) has undertaken extensive archaeological prospection across much of the landscape surrounding Stonehenge. These remote sensing and geophysical surveys have revealed a significant number of new sites and landscape features whilst providing new information on many previously known monuments. The project goal to integrate multimethod mapping over large areas of the landscape has also provided opportunities to re-interpret the landscape context of individual monuments and, in the case of the major henge at Durrington Walls, to generate novel insights into the structure and sequence of a monument which has attracted considerable research attention over many decades. This paper outlines the recent work of the SHLP and the results of survey at Durrington Walls that shed new light on this enigmatic monument including a site ‘hidden’ within the monument.

Pain experienced by many patients with advanced cancer is often not well controlled and community pharmacists are potentially well placed to provide support. The study objective was to explore the views and experiences of patients with advanced cancer about community pharmacies, their services and attitudes towards having a community pharmacist pain medicines consultation. Purposive sampling of GP clinical information systems was used to recruit patients with advanced cancer, living in the community and receiving opioid analgesics in one area of England, UK between January 2015 and July 2016. Thirteen patients had a semi-structured interview which was audio-recorded and transcribed verbatim. Data were analysed deductively and inductively using Framework Analysis and incorporating new themes as they emerged. The framework comprised Pain management, Experiences and expectations, Access to care and Communication. All patients reported using one regular community pharmacy citing convenience, service and staff friendliness as influential factors. The idea of a community pharmacy medicines consultation was acceptable to most patients. The idea of telephone consultations was positively received but electronic media such as Skype was not feasible or acceptable for most. Patients perceived a hierarchy of health professionals with specialist palliative care nurses at the top (due to their combined knowledge of their condition and medicines) followed by GPs then pharmacists. Patients receiving specialist palliative care described pain that was better controlled than those who were not. They thought medicines consultations with a pharmacist could be useful for patients before referral for palliative care. There is a need for pain medicines support for patients with advanced cancer, unmet need appears greater for those not under the care of specialist services. Medicines consultations, in principle, are acceptable to patients both in-person and by telephone, the latter was perceived to be of particular benefit to patients less able to leave the house.

Background: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants in both developed and developing countries. To our knowledge, only a few studies have been reported the clinical features, treatment and outcomes of the GBS disease in China. The severity of neonatal GBS disease in China remains unclear. Population-based surveillance in China is therefore required. Methods: We retrospectively collected data of <3 months old infants with culture-positive GBS in sterile samples from three large urban tertiary hospitals in South China from Jan 2011 to Dec 2014. The GBS isolates and their antibiotic susceptibility were routinely identified in clinical laboratories in participating hospitals. Serotyping and multi-locus sequence typing (MLST) were also conducted for further analysis of the neonatal GBS disease. Results: Total 70 cases of culture-confirmed invasive GBS infection were identified from 127,206 live births born in studying hospitals, giving an overall incidence of 0.55 per 1000 live births (95% confidence interval [CI] 0.44–0.69). They consisted of 49 with early-onset disease (EOD, 0.39 per 1000 live births (95% CI 0.29–0.51)) and 21 with late-onset disease (LOD, 0.17 per 1000 live births (95% CI 0.11–0.25)). The incidence of EOD increased significantly over the studying period. Five infants (4 EOD and 1 LOD) died before discharge giving a mortality rate of 7.1% and five infants (7.1%, 2 EOD and 3 LOD) had neurological sequelae. Within 68 GBS isolates from GBS cases who born in the studying hospitals or elsewhere, serotype III accounted for 77.9%, followed by Ib (14.7%), V (4.4%), and Ia (2.9%). MLST analysis revealed the presence of 13 different sequence types among the 68 GBS isolates and ST-17 was the most frequent sequence type (63.2%). All isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid, while 57.4% and 51.5% were resistant to erythromycin and clindamycin, respectively. Conclusions: This study gains the insight into the spectrum of GBS infection in south China which will facilitate the development of the guidance for reasonable antibiotics usage and will provide evidence for the implementation of potential GBS vaccines in the future.