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Nitrification, the oxidation of ammonia to nitrate, is an essential process in the biogeochemical nitrogen cycle. The first step of nitrification, ammonia oxidation, is performed by three, often co-occurring guilds of chemolithoautotrophs: ammonia-oxidizing bacteria (AOB), archaea (AOA), and complete ammonia oxidizers (comammox). Substrate kinetics are considered to be a major niche-differentiating factor between these guilds, but few AOA strains have been kinetically characterized. Here, the ammonia oxidation kinetic properties of 12 AOA representing all major cultivated phylogenetic lineages were determined using microrespirometry. Members of the genus Nitrosocosmicus have the lowest affinity for both ammonia and total ammonium of any characterized AOA, and these values are similar to previously determined ammonia and total ammonium affinities of AOB. This contrasts previous assumptions that all AOA possess much higher substrate affinities than their comammox or AOB counterparts. The substrate affinity of ammonia oxidizers correlated with their cell surface area to volume ratios. In addition, kinetic measurements across a range of pH values supports the hypothesis that—like for AOB—ammonia and not ammonium is the substrate for the ammonia monooxygenase enzyme of AOA and comammox. Together, these data will facilitate predictions and interpretation of ammonia oxidizer community structures and provide a robust basis for establishing testable hypotheses on competition between AOB, AOA, and comammox.

Aim Burnout amongst junior doctors is an emotive topic, with time pressures during busy on-call shifts negatively impacting efficiency and morale. Historically, within busy surgical firms the most junior team members commonly worked beyond scheduled hours. It has been highlighted within our trust that our IT systems significantly contributed to this. Thus leading to the creation of a clinician-led IT solution, enabling direct access to accurate information at a single point. This study aims to measure the impact of the systems introduction on efficiency and shift experience of our junior doctors. Methods 'Clinical Portal’ was introduced in August 2019. This IT system enables all patient information to be collated in one place, with the added benefit of simplifying the creation of patient lists. Number and duration of Exception Reports (ER) by on-call surgical juniors were measured for two months pre and post intervention. A qualitative survey was also distributed to this cohort to measure satisfaction and experience during on-call shifts within this period. Results Following introduction of 'Clinical Portal', the total length of time included in ERs reduced. Surgical juniors expressed an improvement in their on-call experience, most notably dedicating less time to collating patient information and ward list formation. The overall experience improved despite time required to become proficient at using the new system. Conclusions Streamlining of IT systems used during on-call shifts demonstrates improved efficiency amongst juniors reflected in a reduction of ERs. A direct consequence of these implemented changes is significant improvement in morale amongst our juniors.

The rise and rapid spread of the COVID-19 virus, and subsequent pandemic can be seen to have impacted the health of millions, both directly through infection and indirectly, via numerous factors that have led to delayed treatment of non-COVID related pathology. As a specific example, Tankel et al. showed a 40.7% decrease in the weekly incidence of acute appendicitis, presenting across several centres in Israel, in the first weeks of onset of the COVID-19 pandemic [1]. While the attention of the world and much of the healthcare sector was focussed on the novel virus, other more familiar pathologies did not wait for us to catch up. Acute appendicitis is a common surgical pathology and the most common intra-abdominal emergency in the world [2]. Despite this, the underlying causative pathology is not always clear, and is frequently misunderstood [3]. Within Western Europe, the prevalence has been more or less stable since the year 2000, at 151 per 100,000 person years [4]. The presentation of acute appendicitis is varied, ranging from subclinical and self-resolving to overwhelming sepsis and death. It is estimated that perforated appendicitis is associated with a 5% mortality rate. This is a figure that is vastly different to the mortality rate associated with “acute but not gangrenous” appendicitis, which is 0.1% [5,6]. Due to this spectrum of severity, it is common practice to divide appendicitis into ‘uncomplicated’ and ‘complicated’ categories. Definitions and methods of grouping vary and are the subject of many years of debate [7]. This is beyond the scope of our paper, and our accepted definitions are ‘uncomplicated’ to include simple, focal or suppurative, and ‘complicated’ to include a gangrenous or perforated appendix and any displaying peritonitis or periappendiceal abscess formation [8]. It is well established that an increased time from symptom onset to operative management increases both the risk of progression of pathology and of complications in the post-operative period [8,9]. Existing literature strongly suggests that delaying appendicectomy is associated with a higher rate of complicated appendicitis, and that this is the progression responsible for the subsequently greater morbidity and mortality reported[[8], [9], [10]]. This study aims to investigate the impact of the COVID-19 pandemic on the nature of pathology found in patients undergoing appendicectomy for acute appendicitis at our centre.

Nitrification, the oxidation of ammonia to nitrate, is an essential process in the biogeochemical nitrogen cycle. The first step of nitrification, ammonia oxidation, is performed by three, often co- occurring guilds of chemolithoautotrophs: ammonia-oxidizing bacteria (AOB), archaea (AOA), and complete ammonia oxidizers (comammox). Substrate kinetics are considered to be a major niche-differentiating factor between these guilds, but few AOA strains have been kinetically characterized. Here, the ammonia oxidation kinetic properties of 12 AOA representing all major phylogenetic lineages were determined using microrespirometry. Members of the genus Nitrosocosmicus have the lowest substrate affinity of any characterized AOA, which are similar to previously determined affinities of AOB. This contrasts previous assumptions that all AOA possess much higher substrate affinities than their comammox or AOB counterparts. The substrate affinity of ammonia oxidizers correlated with their cell surface area to volume ratios. In addition, kinetic measurements across a range of pH values strongly supports the hypothesis that – like for AOB – ammonia and not ammonium is the substrate for the ammonia monooxygenase enzyme of AOA and comammox. Together, these data will facilitate predictions and interpretation of ammonia oxidizer community structures and provide a robust basis for establishing testable hypotheses on competition between AOB, AOA, and comammox.

Archaeal and bacterial ammonia oxidizers (AOA and AOB, respectively) initiate nitrification by oxidizing ammonia to hydroxylamine, a reaction catalyzed by ammonia monooxygenase (AMO). AMO enzyme is difficult to purify in its active form, and its structure and biochemistry remain largely unexplored. The bacterial AMO and the closely related particulate methane monooxygenase (pMMO) have a broad range of hydrocarbon cooxidation substrates. This study provides insights into the AMO of previously unstudied archaeal genera, by comparing the response of the archaeal AMO, a bacterial AMO, and pMMO to inhibition by linear 1-alkynes and the aromatic alkyne, phenylacetylene. Reduced sensitivity to inhibition by larger alkynes suggests that the archaeal AMO has a narrower hydrocarbon substrate range than the bacterial AMO, as previously reported for other genera of AOA. Phenylacetylene inhibited the archaeal and bacterial AMOs at different thresholds and by different mechanisms of inhibition, highlighting structural differences between the two forms of monooxygenase., Ammonia monooxygenase (AMO) is a key nitrogen-transforming enzyme belonging to the same copper-dependent membrane monooxygenase family (CuMMO) as the particulate methane monooxygenase (pMMO). The AMO from ammonia-oxidizing archaea (AOA) is very divergent from both the AMO of ammonia-oxidizing bacteria (AOB) and the pMMO from methanotrophs, and little is known about the structure or substrate range of the archaeal AMO. This study compares inhibition by C2 to C8 linear 1-alkynes of AMO from two phylogenetically distinct strains of AOA, “Candidatus Nitrosocosmicus franklandus” C13 and “Candidatus Nitrosotalea sinensis” Nd2, with AMO from Nitrosomonas europaea and pMMO from Methylococcus capsulatus (Bath). An increased sensitivity of the archaeal AMO to short-chain-length alkynes (≤C5) appeared to be conserved across AOA lineages. Similarities in C2 to C8 alkyne inhibition profiles between AMO from AOA and pMMO from M. capsulatus suggested that the archaeal AMO has a narrower substrate range than N. europaea AMO. Inhibition of AMO from “Ca. Nitrosocosmicus franklandus” and N. europaea by the aromatic alkyne phenylacetylene was also investigated. Kinetic data revealed that the mechanisms by which phenylacetylene inhibits “Ca. Nitrosocosmicus franklandus” and N. europaea are different, indicating differences in the AMO active site between AOA and AOB. Phenylacetylene was found to be a specific and irreversible inhibitor of AMO from “Ca. Nitrosocosmicus franklandus,” and it does not compete with NH3 for binding at the active site. IMPORTANCE Archaeal and bacterial ammonia oxidizers (AOA and AOB, respectively) initiate nitrification by oxidizing ammonia to hydroxylamine, a reaction catalyzed by ammonia monooxygenase (AMO). AMO enzyme is difficult to purify in its active form, and its structure and biochemistry remain largely unexplored. The bacterial AMO and the closely related particulate methane monooxygenase (pMMO) have a broad range of hydrocarbon cooxidation substrates. This study provides insights into the AMO of previously unstudied archaeal genera, by comparing the response of the archaeal AMO, a bacterial AMO, and pMMO to inhibition by linear 1-alkynes and the aromatic alkyne, phenylacetylene. Reduced sensitivity to inhibition by larger alkynes suggests that the archaeal AMO has a narrower hydrocarbon substrate range than the bacterial AMO, as previously reported for other genera of AOA. Phenylacetylene inhibited the archaeal and bacterial AMOs at different thresholds and by different mechanisms of inhibition, highlighting structural differences between the two forms of monooxygenase.

Recommendations for mastectomy by multidisciplinary teams (MDTs) may contribute to variation in mastectomy rates. The primary aim of this multicentre prospective observational study was to describe current practice in MDT decision-making for recommending mastectomy. A secondary aim was to determine factors contributing to variation in mastectomy rates.Consecutive patients undergoing mastectomy between 1 June 2015 and 29 February 2016 at participating units across the UK were recruited. Details of neoadjuvant systemic treatment (NST), operative and oncological data, and rationale for recommending mastectomy by MDTs were collected.Overall, 1776 women with breast cancer underwent 1823 mastectomies at 68 units. Mastectomy was advised by MDTs for 1402 (76·9 per cent) of these lesions. The most common reasons for advising mastectomy were large tumour to breast size ratio (530 women, 29·1 per cent) and multicentric disease (372, 20·4 per cent). In total, 202 postmenopausal women with oestrogen receptor-positive (ER+) unifocal tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 173 women (85·6 per cent). Seventy-five women aged less than 70 years with human epidermal growth factor receptor 2-positive (HER2+) tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 45 women (60 per cent).Most mastectomies are advised for large tumour to breast size ratio, but there is an inconsistency in the use of NST to downsize tumours in patients with large ER+ or HER2+ cancers. The application of standardized recommendations for NST could reduce the number of mastectomies advised by MDTs.Las recomendaciones para la mastectomía por equipos multidisciplinarios (multidisciplinary teams, MDTs) podrían contribuir a explicar la diferencia en las tasas de mastectomía. El objetivo primario de este estudio observacional prospectivo y multicéntrico fue describir la práctica actual en la toma de decisiones de los MDT para recomendar la mastectomía. El objetivo secundario fue determinar factores que contribuyen a la variación en las tasas de mastectomía. MÉTODOS: Se reclutaron pacientes consecutivas sometidas a mastectomía entre el 1 de junio de 2015 y el 29 de febrero de 2016 en las unidades participantes de todo el Reino Unido. Se recogieron datos del preoperatorio, tratamiento neoadyuvante sistémico (neoadjuvant systemic treatment, NST), quirúrgicos y oncológicos, así como la justificación de los MDT para recomendar la mastectomía.Un total de 1.776 pacientes fueron sometidas a 1.823 mastectomías en 68 unidades. La mastectomía fue recomendada por los MDTs en 1.402 (76,9%) de estas mujeres. Las razones más frecuentes para recomendar la mastectomía fueron la elevada proporción entre el tamaño del tumor y el de la mama (530; 29,1%) y la enfermedad multicéntrica (372; 20,4%). En total, a 202 mujeres postmenopáusicas con tumores unifocales positivos para receptores de estrógenos (ER+) se les recomendó la mastectomía y no se les ofreció NST; debido a una elevada proporción entre el tamaño del tumor y de la mama en 173 (86%) pacientes. A 75 mujeres de70 años con tumores positivos para el human epidermal growth factor receptor 2 (HER2+) se les recomendó la mastectomía y no se les ofreció NST; debido a una elevada proporción entre el tamaño del tumor y de la mama en 45 (60%) mujeres. CONCLUSIÓN: La mayoría de las mastectomías se recomendaron en casos con una elevada proporción entre el tamaño del tumor y el de la mama, pero existe una inconsistencia en la utilización de la NST para reducir el tamaño del tumor en pacientes con grandes cánceres ER+ o HER2+. La aplicación de recomendaciones estandarizadas para la NST podría reducir el número de mastectomía recomendadas por los MDT.