A time of change

An investigation of classroom environment factors affecting pupil progress in mathematics during the transition from primary to secondary schoolThe study took place in North East Scotland, a rural area with diverse industries. The sample of pupils selected for the study was from a small group of primary schools associated with three secondary schools. A number of quantitative and qualitative measures were developed to collect data for the study: a number of mathematical tests to determine the mathematical progress made by pupils between Primary 7 and Secondary I; pupil and teacher questionnaires and an observer's schedule. Perceptions from each of these measures were used to 'describe' the classroom environment. The measures were tested through a pilot study and adjustments made for their use in main research study. Formal and informal interviews with teachers and pupils were also used to provide additional depth to classroom profiles.The analysis of the quantitative data enabled pupil progress to be confirmed for most sample pupils. It was also possible to identify small groups of pupils who improved and regressed exceptionally. By focusing on these groups, factors affecting exceptional improvement were highlighted. Some of these factors were linked to primary school experience, for example,teacher interest and pupil method of working. The main classroom environment factors affecting pupil progress were pupil perception of performance and a high level of teacher/pupil interaction. Pupil placement in school attainment groupings (sets) was related to pupil progress, mostly regression. No single factor was associated with exceptional regression. The construction of a number of primary and secondary classroom environment profiles showed the strong impact of a highly positive environment on pupil progress

The Effect of Short-Term Vitamin D Supplementation on Calcium Status in Vitamin D Insufficient Renal Transplant Recipients at Risk of Hypercalcaemia

Vitamin D insufficiency is highly prevalent amongst renal transplant recipients and in observational studies is associated with adverse outcomes. Hypercalcaemia, usually due to persistent hyperparathyroidism, also commonly occurs in this population and often coexists with vitamin D insufficiency. However, concern that vitamin D supplementation might exacerbate the pre-existing hypercalcaemia often leads clinicians to avoid vitamin D supplementation in such patients. This feasibility study aimed to quantify the effect on serum calcium of short-term low- dose cholecalciferol supplementation in a group of renal transplant recipients with a recent history of serum calcium levels >10 mg/dL

Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit

Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5' UTR of mRNA

Cytoplasmic innate immune sensing by the caspase-4 non-canonical inflammasome promotes cellular senescence

Cytoplasmic recognition of microbial lipopolysaccharides (LPS) in human cells is elicited by the caspase-4 and caspase-5 noncanonical inflammasomes, which induce a form of inflammatory cell death termed pyroptosis. Here we show that LPS-mediated activation of caspase-4 also induces a stress response promoting cellular senescence, which is dependent on the caspase-4 substrate gasdermin-D and the tumor suppressor p53. Furthermore, we found that the caspase-4 noncanonical inflammasome is induced and assembled in response to oncogenic RAS signaling during oncogene-induced senescence (OIS). Moreover, targeting caspase-4 expression in OIS showed its critical role in the senescence-associated secretory phenotype and the cell cycle arrest induced in cellular senescence. Finally, we observed that caspase-4 induction occurs in vivo in mouse models of tumor suppression and ageing. Altogether, we are showing that cellular senescence is induced by cytoplasmic LPS recognition by the noncanonical inflammasome and that this pathway is conserved in the cellular response to oncogenic stress.This work was funded by Cancer Research UK (CRUK) (C47559/A16243 Training & Career Development Board - Career Development Fellowship), the University of Edinburgh Chancellor’s Fellowship R42576 MRC, and the Ministry of Science and Innovation of the Government of Spain (Proyecto PID2020-117860GB-I00 financiado por MCIN/ AEI /10.13039/501100011033). J.C.A. was supported by CRUK, the University of Edinburgh and is supported by the Spanish National Research Council (CSIC). P.H., I.F.D and N.T. were funded by the University of Edinburgh. A.Q. was funded by CRUK. J.F.P and A.B.L. are funded by NIH grants: 1R01AG068048-01; P01 AG062413; 1UG3 CA268103-01. J.B. was funded by BBSRC (BB/K017314/1). V.S-B is supported by funding from the University of Edinburgh and Medical Research Council (MC_UU_00009/2). F.R.M is funded by a Wellcome Trust Clinical Research Fellowship through the Edinburgh Clinical Academic Track (ECAT) (203913/Z/16/Z). M.M. was supported by CRUK Edinburgh Centre Award (C157/A25140). V.G.B. is funded by CRUK (C157/A24837) and the University of Edinburgh

Determination and analysis of time series of CFC-11 (CCl3F) from FTIR solar spectra, in situ observations, and model data in the past 20 years above Jungfraujoch (46◦N), Lauder (45◦S), and Cape Grim (40◦S) stations

Trichlorofluoromethane (CFC-11) is the second most important chlorofluorocarbons (CFCs) in the Earth’s atmosphere. CFCs are long-lived chemicals which were exclusively produced by the industry and broadly used as aerosol spray propellants, refrigerants, inflating and insulating agents in the production of foam materials, as well as solvents. CFCs are transported into the stratosphere where they are photodissociated by UV radiation, releasing chlorine atoms that catalytically destroy stratospheric ozone. The atmospheric concentration of CFC-11 has declined in response to the phase-out of its production by the Montreal Protocol. Nevertheless, this atmospheric concentration decline suffered a slowdown around 2012 due to emissions from non-reported production. Since CFC-11 remains one of the most important ozone-depleting halocarbons, its continuous monitoring is essential. We present the CFC-11 total column time series (2000 – 2020) retrieved in a consistent way from ground-based high-resolution solar absorption Fourier transform infrared (FTIR) spectra. These observations were recorded at two mid-latitude stations of the Network for the Detection of Atmospheric Composition Change (NDACC.org): the Jungfraujoch station (Northern Hemisphere; 46.5⁰N) and the Lauder station (Southern Hemisphere; 45⁰S). These time series were compared with Cape Grim station (40.7⁰S) in situ surface observations conducted within the Advanced Global Atmospheric Gases Experiment (AGAGE) network and with total column datasets calculated by the TOMCAT/SLIMCAT 3-D chemical transport model implementing the unreported emissions. Trend analyses were performed in order to identify and characterise the timing and magnitude of the trend change in both hemispheres. The observations are consistent with the model results and confirm the slowdown in the CFC-11 atmospheric concentration decay, since ≈ 2011 in the Northern Hemisphere, and since ≈ 2014 in the Southern Hemisphere

‘Necessity is the mother of invention’: Specialist palliative care service innovation and practice change in response to COVID-19. Results from a multinational survey (CovPall)

Background:Specialist palliative care services have a key role in a whole system response to COVID-19, a disease caused by the SARS-CoV-2 virus. There is a need to understand service response to share good practice and prepare for future care.Aim:To map and understand specialist palliative care services innovations and practice changes in response to COVID-19.Design:Online survey of specialist palliative care providers (CovPall), disseminated via key stakeholders. Data collected on service characteristics, innovations and changes in response to COVID-19. Statistical analysis included frequencies, proportions and means, and free-text comments were analysed using a qualitative framework approach.Setting/participants:Inpatient palliative care units, home nursing services, hospital and home palliative care teams from any country.Results:Four hundred and fifty-eight respondents: 277 UK, 85 Europe (except UK), 95 World (except UK and Europe), 1 missing country. 54.8% provided care across 2+ settings; 47.4% hospital palliative care teams, 57% in-patient palliative care units and 57% home palliative care teams. The crisis context meant services implemented rapid changes. Changes involved streamlining, extending and increasing outreach of services, using technology to facilitate communication, and implementing staff wellbeing innovations. Barriers included; fear and anxiety, duplication of effort, information overload and funding. Enablers included; collaborative teamwork, staff flexibility, a pre-existing IT infrastructure and strong leadership.Conclusions:Specialist palliative care services have been flexible, highly adaptive and have adopted low-cost solutions, also called ‘frugal innovations’, in response to COVID-19. In addition to financial support, greater collaboration is essential to minimise duplication of effort and optimise resource use

Symptom management in people dying with COVID-19: multinational observational study

Objectives To describe multinational prescribing practices by palliative care services for symptom management in patients dying with COVID-19 and the perceived effectiveness of medicines.Methods We surveyed specialist palliative care services, contacted via relevant organisations between April and July 2020. Descriptive statistics for categorical variables were expressed as counts and percentages. Content analysis explored free text responses about symptom management in COVID-19. Medicines were classified using British National Formulary categories. Perceptions on effectiveness of medicines were grouped into five categories; effective, some, limited or unclear effectiveness, no effect.Results 458 services responded; 277 UK, 85 rest of Europe, 95 rest of the world, 1 missing country. 358 services had managed patients with confirmed or suspected COVID-19. 289 services had protocols for symptom management in COVID-19. Services tended to prescribe medicines for symptom control comparable to medicines used in people without COVID-19; mainly opioids and benzodiazepines for breathlessness, benzodiazepines and antipsychotics for agitation, opioids and cough linctus for cough, paracetamol and non-steroidal anti-inflammatory drugs for fever, and opioids and paracetamol for pain. Medicines were considered to be mostly effective but varied by patient’s condition, route of administration and dose.Conclusions Services were largely consistent in prescribing for symptom management in people dying with COVID-19. Medicines used prior to COVID-19 were mostly considered effective in controlling common symptoms

Experiences of staff providing specialist palliative care during COVID-19: a multiple qualitative case study

Objective: To explore the experiences of, and impact on, staff working in palliative care during the COVID-19 pandemic. Design: Qualitative multiple case study using semi-structured interviews between November 2020 and April 2021 as part of the CovPall study. Data were analysed using thematic framework analysis. Setting: Organisations providing specialist palliative services in any setting. Participants: Staff working in specialist palliative care, purposefully sampled by the criteria of role, care setting and COVID-19 experience. Main outcome measures: Experiences of working in palliative care during the COVID-19 pandemic. Results: Five cases and 24 participants were recruited (n = 12 nurses, 4 clinical managers, 4 doctors, 2 senior managers, 1 healthcare assistant, 1 allied healthcare professional). Central themes demonstrate how infection control constraints prohibited and diluted participants’ ability to provide care that reflected their core values, resulting in experiences of moral distress. Despite organisational, team and individual support strategies, continually managing these constraints led to a ‘crescendo effect’ in which the impacts of moral distress accumulated over time, sometimes leading to burnout. Solidarity with colleagues and making a valued contribution provided ‘moral comfort’ for some. Conclusions: This study provides a unique insight into why and how healthcare staff have experienced moral distress during the pandemic, and how organisations have responded. Despite their experience of dealing with death and dying, the mental health and well-being of palliative care staff was affected by the pandemic. Organisational, structural and policy changes are urgently required to mitigate and manage these impacts

Clinical Oncology Society of Australia: Position statement on cancer-related malnutrition and sarcopenia

© 2020 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia. This position statement describes the recommendations of the Clinical Oncology Society of Australia (COSA) regarding management of cancer-related malnutrition and sarcopenia. A multidisciplinary working group completed a review of the literature, focused on evidence-based guidelines, systematic reviews and meta-analyses, to develop recommendations for the position statement. National consultation of the position statement content was undertaken through COSA members. All people with cancer should be screened for malnutrition and sarcopenia in all health settings at diagnosis and as the clinical situation changes throughout treatment and recovery. People identified as “at risk” of malnutrition or with a high-risk cancer diagnosis or treatment plan should have a comprehensive nutrition assessment; people identified as “at risk” of sarcopenia should have a comprehensive evaluation of muscle status using a combination of assessments for muscle mass, muscle strength and function. All people with cancer-related malnutrition and sarcopenia should have access to the core components of treatment, including medical nutrition therapy, targeted exercise prescription and physical and psychological symptom management. Treatment for cancer-related malnutrition and sarcopenia should be individualised, in collaboration with the multidisciplinary team (MDT), and tailored to meet needs at each stage of cancer treatment. Health services should ensure a broad range of health care professionals across the MDT have the skills and confidence to recognise malnutrition and sarcopenia to facilitate timely referrals and treatment. The position statement is expected to provide guidance at a national level to improve the multidisciplinary management of cancer-related malnutrition and sarcopenia