Preprosubtilisin Carlsberg processing and secretion is blocked after deletion of amino acids 97-101 in the mature part of the enzyme

During an investigation into the substrate specificity and processing of subtilisin Carlsberg from Bacillus licheniformis, two major independent findings were made: (i) as has been shown previously, a stretch of five amino acids (residues 97-101 of the mature enzyme) that loops out into the binding cleft is involved in substrate binding by subtilisin Carlsberg. In order to see whether this loop element also determines substrate specificity, the coding region for these five amino acids was deleted from the cloned gene for subtilisin Carlsberg by site-directed mutagenesis. Unexpectedly the resulting mutant preproenzyme (P42c, Mr=42 kDa) was not processed to the mature form (Mr = 30 kDa) and was not released into the medium by a proteasedeficient B. subtilis host strain; rather, it accumulated in the cell membrane. This result demonstrates that the integrity of this loop element, which is very distant from the processing cleavage sites in the preproenzyme, is required for secretion of subtilisin Carlsberg. (ii) In culture supernatants from B. subtilis harbouring the cloned wild-type subtilisin Carlsberg gene the transient appearance (at 0-3 h after onset of stationary phase) of a processing intermediate (P38c, Mr = 38 kDa) oftbis protease could be demonstrated. P38c very probably represents a genuine proform of subtilisin Carlsberg

Single- and double-scattering production of four muons in ultraperipheral PbPb collisions at the Large Hadron Collider

We discuss production of two $\mu^+\mu^-$ pairs in ultraperipheral ultrarelativistic heavy ion collisions at the LHC. We take into account electromagnetic (two-photon) double-scattering production and for a first time direct $\gamma\gamma$ production of four muons in one scattering. We study the unexplored process $\gamma \gamma \to \mu^+\mu^-\mu^+\mu^-$. We present predictions for total and differential cross sections. Measurable nuclear cross sections are obtained and corresponding differential distributions and counting rates are presented.Comment: 13 pages, 11 figures, 1 tabl

Advance care planning for patients with advanced illnesses attending hospital outpatient clinics study: A study protocol for a randomised controlled trial

© Author(s) (or their employer(s)) 2019. Introduction It is unclear whether advance care planning (ACP) undertaken with patients living in the community can improve patient care and avoid unwanted interventions and hospital admissions. We have designed a randomised controlled trial (RCT) to examine if ACP undertaken with patients with advanced illnesses attending hospital outpatient clinics can reduce unplanned hospital admissions and improve patient and caregiver well-being. Methods and analysis Pragmatic RCT involving patients from subspecialty outpatient clinics at five clinical sites in Sydney, Australia. Participants will be ≥18 years screened as potentially having palliative care needs and at risk of dying in 6-12 months. The patients will be randomised to intervention or control group. Intervention group will undertake ACP discussions facilitated by a trained health professional. The control group will receive written information on ACP, representing the current standard of care. The primary outcome is the number of unplanned hospital admissions at the 6-month follow-up. Secondary outcomes include: (i) patient's health-related quality-of-life and quality of chronic disease care; (ii) caregiver's health-related quality-of-life and caregiver burden and (iii) other health outcomes including ambulance usage, emergency department presentations, hospital admissions, resuscitation attempts, intensive care unit admissions, deaths, documentation of patient wishes in patient records and audit of ACP discussions and documents. The staff's self-reported attitudes and knowledge of ACP will also be measured. The data will be collected using self-report questionnaires, hospital records audit, audit of ACP documentation and data linkage analysis. Semistructured interviews and focus group discussions with patients, caregivers and healthcare professionals will explore the acceptability and feasibility of the intervention. Ethics and dissemination Approved by South-East Sydney Local Health District Human Research Ethics Committee and NSW Population and Health Services Research Ethics Committee. Results will be disseminated via conference presentations, journal publications, seminars and invited talks

What constitutes brilliant aged care? : a qualitative study of practices that exceed expectation

Aim: This study aimed to explore what constitutes brilliant aged care. Background: Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care—practices that exceeded expectation. Design: The methodology for this study was informed by grounded theory, under-pinned by constructionism to socially construct meaning. Methods: This study invited nominations for a Brilliant Award via a survey, and inter-views with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency. Results: According to participants, brilliant aged care involved being relationally at-tuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise. Conclusions: This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation. Relevance to Clinical Practice: For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms. Patient or Public Contribution: The nominees, who included carers, were invited to participate in workshops with other carers and older people to co-design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Disease Focused Integrated Care – a New Model of Healthcare Delivery for the Treatment of Skin Cancer

Introduction: As the most common cancer in Australia, skin cancer generates a considerable health burden. This study outlines the establishment of a new model of integrated care for the diagnosis and management of skin cancer. Methods: A new model of integrated care was established to provide access to all aspects of skin cancer management. General practitioners (GPs) were upskilled through hands-on training and a 6-month skin cancer education program and partnered with specialist Dermatologists and Plastic Surgeons co-located in the same clinic. Data including median wait times between the initial consultation and treatment were prospectively collected and compared patients seen through the integrated pathway to patients referred from their primary GP to specialist Dermatologists and Plastic Surgeons directly (non-integrated pathway). The percentage of patients needing co-consultation with a specialist in the integrated pathway was also measured over time. Results: A total of 25341 patients were seen from the commencement of the clinic in August 2015 to June 2021. In 2017 and 2018 the median wait time to be treated was 7 days for the integrated model compared to 54 days (2017) and 46 days (2018) for non-integrated care (p < 0.0001). The percentage of GPs requesting specialist co-consultations for assessment of skin cancer fell from 98% in 2015, to 5.6% in 2021. Histopathology shows that 66% of lesions excised by GPs in this model were malignant or pre-malignant. Conclusions: This study firstly shows a significant reduction in time to treatment in an integrated skin cancer model over traditional models of health. Secondly it demonstrates GP upskilling over time in the integrated program. Integrating GP and specialist medical practitioners in the treatment of skin cancer offers potential for more efficient, accessible, and affordable care. This cooperative, co-located model may provide a template for the integrating the management of other conditions

Dementia-friendly interventions to improve the care of people living with dementia admitted to hospitals: a realist review

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objectives: To identify features of programmes and approaches to make healthcare delivery in secondary healthcare settings more dementia friendly, providing a context-relevant understanding of how interventions achieve outcomes for people living with dementia. Design: A realist review conducted in three phases (1) stakeholder interviews and scoping of the literature to develop an initial programme theory for providing effective dementia care; (2) structured retrieval and extraction of evidence; (3) analysis and synthesis to build and refine the programme theory. Data sources: PubMed, CINAHL, Cochrane Library, NHS Evidence, Scopus, grey literature. Eligibility criteria: Studies reporting interventions and approaches to make hospital environments more dementia friendly. Studies not reporting patient outcomes or contributing to the programme theory were excluded. Results: Phase 1 combined findings from 15 stakeholder interviews and 22 publications to develop candidate programme theories. Phases 2 and 3 identified and synthesised evidence from 28 publications. Prominent context-mechanism-outcome configurations were identified to explain what supported dementia-friendly healthcare in acute settings. Staff capacity to understand the behaviours of people living with dementia as communication of an unmet need, combined with a recognition and valuing of their role in their care prompted changes to care practices. Endorsement from senior management gave staff confidence and permission to adapt working practices to provide good dementia care. Key contextual factors were the availability of staff and an alignment of ward priorities to value person-centred care approaches. Preoccupation with risk generated responses that were likely to restrict patient choice and increase their distress. Conclusions: This review suggests strategies such as dementia awareness training alone will not improve dementia care or outcomes for patients with dementia. Instead, how staff are supported to implement learning and resources by senior team members with dementia expertise is a key component for improving care practices and patient outcomes. PROSPERO Trial Registration Number: CRD42015017562Peer reviewedFinal Published versio

The PERMA well-being model and music facilitation practice: Preliminary documentation for well-being through music provision in Australian schools

The aim of this study was to consider how we can invest in music-making to promote well-being in school contexts. Web-based data collection was conducted where researchers identified 17 case studies that describe successful music programs in schools in Australia. The researchers aligned content from these case studies into the five categories of the PERMA well-being model: Positive emotions, Engagement, Relationships, Meaning, and Accomplishment, in order to understand how each well-being element was realised through the music programs. The results indicate that the element of the PERMA well-being model that relates to relationships was described most often. Collaboration and partnership between students, teachers, and staff in schools, and local people in the community such as parents, local entrepreneurs, and musicians were repeatedly identified as a highly significant contributing factor in the success of the music program. The school leaders? roles in providing opportunities for students to experience musical participation and related activities (engagement) and valuing these experiences (meaning) were also crucial in the facilitation of the music programs. The findings of this study indicate that tailored music and relationship-centred music programs in schools not only increase skills and abilities of the students, but also improve the psychosocial well-being of the students and the community