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The large-scale conversion of N 2 and H 2 into NH 3 (refs.  1 , 2 ) over Fe and Ru catalysts 3 for fertilizer production occurs through the Haber–Bosch process, which has been considered the most important scientific invention of the twentieth century 4 . The active component of the catalyst enabling the conversion was variously considered to be the oxide 5 , nitride 2 , metallic phase or surface nitride 6 , and the rate-limiting step has been associated with N 2 dissociation 7 – 9 , reaction of the adsorbed nitrogen 10 and also NH 3 desorption 11 . This range of views reflects that the Haber–Bosch process operates at high temperatures and pressures, whereas surface-sensitive techniques that might differentiate between different mechanistic proposals require vacuum conditions. Mechanistic studies have accordingly long been limited to theoretical calculations 12 . Here we use X-ray photoelectron spectroscopy—capable of revealing the chemical state of catalytic surfaces and recently adapted to operando investigations 13 of methanol 14 and Fischer–Tropsch synthesis 15 —to determine the surface composition of Fe and Ru catalysts during NH 3 production at pressures up to 1 bar and temperatures as high as 723 K. We find that, although flat and stepped Fe surfaces and Ru single-crystal surfaces all remain metallic, the latter are almost adsorbate free, whereas Fe catalysts retain a small amount of adsorbed N and develop at lower temperatures high amine (NH x ) coverages on the stepped surfaces. These observations indicate that the rate-limiting step on Ru is always N 2 dissociation. On Fe catalysts, by contrast and as predicted by theory 16 , hydrogenation of adsorbed N atoms is less efficient to the extent that the rate-limiting step switches following temperature lowering from N 2 dissociation to the hydrogenation of surface species. Using X-ray photoelectron spectroscopy, the surface composition of iron and ruthenium catalysts during ammonia synthesis at pressures up to 1 bar and temperatures as high as 723 K can be revealed.

While Au electro‐oxidation in acidic aqueous media on a phenomenological level proceeds directly from Au(0) to Au(III), it has previously been suggested that Au(I) states are intermediate species of the oxidation mechanism. Here, additional evidence for the transient Au(I) is provided by the probing the electro‐oxidation of Au electrode operando in a pH = 3 perchloric acid (HClO4) electrolyte by high‐energy‐resolution fluorescence‐detected X‐ray absorption near‐edge structure (HERFD–XANES) at potentials up to 1.8 V versus the reversible hydrogen electrode (RHE). The perchlorate ions (ClO4−) in the electrolyte are used as sacrificial oxidizing agents. The reduced perchlorate compounds in turn produce chloride ions, which react with Au ions to form Au–Cl compounds. The operando HERFD–XANES detects and identifies the chlorinated compounds as surficial Au(I), present during the early stages of Au oxidation. It is further inferred that Au(I) is accessed by the electrolyte. These observations are consistent with the previously hypothesized route for Au electro‐oxidation involving charge transfer after a dipole‐induced place‐exchange step. Formation of surficial Au(I)Cl during electro‐oxidation reveals that Au(+I) is present as an intermediate during oxidation toward Au(+III) oxides. The Au‐Cl deposition is observed operando by high‐energy‐resolution fluorescence‐detected near‐edge X‐ray absorption fine structure. These observations add to the evidence for step‐wise charge transfer in Au electro‐oxidation and imply that the charge transfer step occurs after a dipole‐induced place exchange step.

BackgroundTimely diagnosis of heart failure (HF) and rapid optimisation of guideline-directed medication therapy (GDMT) improves patients qualities of life, reducing mortality and morbidity. Previous papers describe the role of pharmacists in medication optimisation, but not in the diagnosis of HF.AimTo describe the development, implementation, and evaluation of pharmacist-led heart failure clinics with respect to time from referral to diagnosis, time from diagnosis to first review with a specialist, and the proportion receiving optimal GDMT 180 days after diagnosis.SettingCommunity outpatient clinics in rural west Wales, United Kingdom.DevelopmentTwo experienced non-medical prescribing pharmacists, one of whom had additional diagnostic qualifications in cardiology, delivered the clinic.ImplementationPatients referred with suspected HF were risk-stratified to urgent (within 14 days of referral) or routine (within 42 days) review, based on natriuretic peptide levels. Patients attended the clinic for assessment, including physical examination, electrocardiogram, and echocardiogram. Those with HF with reduced ejection fraction were initiated on drug treatment and referred to the follow-up pharmacist-led GDMT clinic.EvaluationA sample of 100 patients was evaluated (50 from pre-existing and 50 from new service). Median time from referral to diagnosis reduced from 61 days (IQR 47–115) to 16 days (IQR 10.5–27.5) for urgent and 19 days (IQR 11.5–33) for routine. Median time to first appointment following diagnosis reduced from 54 days (IQR 36–60.5) to 14 days (IQR 9.75–28.75) (p value < 0.0001), and proportion of patients achieving GDMT at 180 days following diagnosis improved from 24 to 86% (p value < 0.0001).ConclusionThis pharmacist HF diagnostic clinic and medication optimisation clinic improved time to diagnosis, time to first specialist review, and proportion of patients’ achieving GDMT optimisation in a rural healthcare setting.

Efficient charge extraction in solar energy conversion devices requires materials that are capable of generating long-lived charge carriers. However, carrier lifetimes vary by orders of magnitude between photoabsorbers and there is no blueprint for the targeted design of materials with intrinsically long lifetimes. Here, we establish a fundamental link between the carrier lifetime and the electronic configuration of transition metal oxides (TMOs). By comparing their deactivation pathways across a range of electronic configurations, we identify a sub-ps relaxation mechanism via metal-centred ligand field (LF) states. These LF states open localised recombination channels that compromise charge and quantum yields in open d-shell TMOs (e.g., Fe2O3, Co3O4, Cr2O3, NiO), which is more reminiscent of molecular complexes than crystalline semiconductors. In contrast, in TMOs with d0 or d10 electronic configurations (e.g., TiO2, BiVO4), the absence of LF states enables larger yields of long-lived charges and thus more efficient photocatalysis. Notably, our results suggest that charge localisation in the form of polarons can mitigate rapid LF deactivation. These trends translate to other metal-containing semiconductors and open a new pathway to design absorbers with well-controlled non-radiative recombination channels for applications including photovoltaics, photocatalysis, and communication devices.

For their safety I asked my friend, John, to bring his chainsaw.

School-based COVID-19 contacts in England have been asked to self-isolate at home, missing key educational opportunities. We trialled daily testing of contacts as an alternative to assess whether this resulted in similar control of transmission, while allowing more school attendance. We did an open-label, cluster-randomised, controlled trial in secondary schools and further education colleges in England. Schools were randomly assigned (1:1) to self-isolation of school-based COVID-19 contacts for 10 days (control) or to voluntary daily lateral flow device (LFD) testing for 7 days with LFD-negative contacts remaining at school (intervention). Randomisation was stratified according to school type and size, presence of a sixth form, presence of residential students, and proportion of students eligible for free school meals. Group assignment was not masked during procedures or analysis. Coprimary outcomes in all students and staff were COVID-19-related school absence and symptomatic PCR-confirmed COVID-19, adjusted for community case rates, to estimate within-school transmission (non-inferiority margin <50% relative increase). Analyses were done on an intention-to-treat basis using quasi-Poisson regression, also estimating complier average causal effects (CACE). This trial is registered with the ISRCTN registry, ISRCTN18100261. Between March 18 and May 4, 2021, 204 schools were taken through the consent process, during which three decided not to participate further. 201 schools were randomly assigned (control group n=99, intervention group n=102) in the 10-week study (April 19–May 10, 2021), which continued until the pre-appointed stop date (June 27, 2021). 76 control group schools and 86 intervention group schools actively participated; additional national data allowed most non-participating schools to be included in analysis of coprimary outcomes. 2432 (42·4%) of 5763 intervention group contacts participated in daily contact testing. There were 657 symptomatic PCR-confirmed infections during 7 782 537 days-at-risk (59·1 per 100 000 per week) in the control group and 740 during 8 379 749 days-at-risk (61·8 per 100 000 per week) in the intervention group (intention-to-treat adjusted incidence rate ratio [aIRR] 0·96 [95% CI 0·75–1·22]; p=0·72; CACE aIRR 0·86 [0·55–1·34]). Among students and staff, there were 59 422 (1·62%) COVID-19-related absences during 3 659 017 person-school-days in the control group and 51 541 (1·34%) during 3 845 208 person-school-days in the intervention group (intention-to-treat aIRR 0·80 [95% CI 0·54–1·19]; p=0·27; CACE aIRR 0·61 [0·30–1·23]). Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures. UK Government Department of Health and Social Care.

The mammalian target of rapamycin complex 1 (mTORC1) is the key signaling hub that regulates cellular protein homeostasis, growth, and proliferation in health and disease. As a prerequisite for activation of mTORC1 by hormones and mitogens, there first has to be an available pool of intracellular amino acids. Arginine, an amino acid essential during mammalian embryogenesis and early development is one of the key activators of mTORC1. Herein, we demonstrate that arginine acts independently of its metabolism to allow maximal activation of mTORC1 by growth factors via a mechanism that does not involve regulation of mTORC1 localization to lysosomes. Instead, arginine specifically suppresses lysosomal localization of the TSC complex and interaction with its target small GTPase protein, Rheb. By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of Rheb by TSC. Arginine cooperates with growth factor signaling which further promotes dissociation of TSC2 from lysosomes and activation of mTORC1. Arginine is the main amino acid sensed by the mTORC1 pathway in several cell types including human embryonic stem cells (hESCs). Dependence on arginine is maintained once hESCs are differentiated to fibroblasts, neurons, and hepatocytes, highlighting the fundamental importance of arginine-sensing to mTORC1 signaling. Together, our data provide evidence that different growth promoting cues cooperate to a greater extent than previously recognized to achieve tight spatial and temporal regulation of mTORC1 signaling. Cells need to be able to sense and respond to signals from their environment. A group (or complex) of conserved proteins called mTORC1 acts a key signaling hub that regulates cell growth and many other processes. This complex can be activated by many different signals from outside the cell. However, mTORC1 can only be activated by these signals if there is also a good supply of amino acids – which are needed to make new proteins – within the cell. The amino acids are thought to be presented to mTORC1 on the outer surface of cellular compartments known as lysosomes. A protein called Rheb on the surface of the lysosomes activates mTORC1, while a protein complex called TSC inhibits the activity of Rheb to regulate mTORC1 activity. Previous studies have shown that some amino acids influence whether mTORC1 can be activated by affecting whether it is localized to the lysosomes or not. Here, Carroll et al. explored how an amino acid called arginine regulates mTORC1. The experiments show that arginine is the major amino acid that influences whether mTORC1 can be activated in several different types of human cell. When cells were deprived of arginine, the activity of the complex was strongly suppressed. However, microscopy showed that arginine had no effect on whether mTORC1 was found at the lysosomes or not, which suggests that arginine might be acting in a different way to other amino acids. Further experiments found that a lack of arginine led to an increase in the number of TSC complexes at the lysosomes. This led to the inhibition of Rheb and therefore prevented mTORC1 from being activated. Together, Carroll et al.’s findings provide evidence that the different signals that regulate mTORC1 signaling cooperate to a greater extent than previously thought. A future challenge will be to understand the molecular details of how the arginine is detected.

Context: Significant attention has been directed toward addressing health inequities at the population health and systems levels, yet little progress has been made in identifying approaches to reduce health inequities through clinical care, particularly in a primary health care context. Although the provision of equity-oriented health care (EOHC) is widely assumed to lead to improvements in patients' health outcomes, little empirical evidence supports this claim. To remedy this, we tested whether more EOHC predicts more positive patient health outcomes and identified selected mediators of this relationship. Methods: Our analysis uses longitudinal data from 395 patients recruited from 4 primary health care clinics serving people living in marginalizing conditions. The participants completed 4 structured interviews composed of self-report measures and survey questions over a 2-year period. Using path analysis techniques, we tested a hypothesized model of the process through which patients' perceptions of EOHC led to improvements in self-reported health outcomes (quality of life, chronic pain disability, and posttraumatic stress [PTSD] and depressive symptoms), including particular covariates of health outcomes (age, gender, financial strain, experiences of discrimination). Findings: Over a 24-month period, higher levels of EOHC predicted greater patient comfort and confidence in the health care patients received, leading to increased confidence to prevent and manage their health problems, which, in turn, improved health outcomes (depressive symptoms, PTSD symptoms, chronic pain, and quality of life). In addition, financial strain and experiences of discrimination had significant negative effects on all health outcomes. Conclusions: This study is among the first to demonstrate empirically that providing more EOHC predicts better patient health outcomes over time. At a policy level, this research supports investments in equity-focused organizational and provider-level processes in primary health care as a means of improving patients' health, particularly for those living in marginalizing conditions. Whether these results are robust in different patient groups and across a broader range of health care contexts requires further study.

BackgroundPolypharmacy is associated with the prescription of inappropriate medications and avoidable medication-related harm. A novel pharmacist-led intervention aims to identify and resolve inappropriate medication prescriptions in older adults with polypharmacy.AimTo conduct a preliminary feasibility assessment of the intervention in primary care, testing whether specific components of the intervention procedures and processes can be executed as intended.MethodThe mixed-methods study was approved by the New Zealand Health and Disability Ethics Committees and public health agency. Patients from a New Zealand general practice clinic were recruited over 4 weeks to receive the intervention. The preliminary feasibility assessment included measures of intervention delivery, patient-reported outcome measures, and perspectives from ten patients and six clinicians. Data were analysed quantitatively and qualitatively to determine if a full-scale intervention trial is warranted. The study's progression criteria were based on established research and guided the decision-making process.ResultsThe intervention met the study's progression criteria, including patient recruitment, retention, and adherence to the intervention procedures. However, several modifications were identified, including: (1) enhancing patient recruitment, (2) conducting a preliminary meeting between the patient and pharmacist, (3) supporting pharmacists in maintaining a patient-centred approach, (4) reviewing the choice of patient-reported outcome measure, (5) extending the 8-week follow-up period, (6) allocating more time for pharmacists to conduct the intervention.ConclusionThe study found the intervention feasible; however, additional development is required before progressing to a full-scale trial. This intervention has the potential to effectively reduce medication-related harm and improve outcomes for older adults with polypharmacy.Trial registration number ACTRN12621000268842 Date registered: 11/03/2021