Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Mortality rates in people presenting with a new diabetes-related foot ulcer: a cohort study with implications for management.

Aims/hypothesis: People with diabetes-related foot ulcers (DFUs) have high mortality rates. This analysis assesses the impact of selected risk factors on short-term mortality using a population registered in the National Diabetes Foot Care Audit (NDFA).

Methods: Mortality rates at 12, 26 and 52 weeks was assessed in people with a new DFU registered by a specialist diabetes footcare service in the NDFA in England and Wales between April 2017 and March 2022.

Trends in hospitalization for cardio-renal disease and mortality in people with type 1 diabetes in England, 2009-2019.

Aim: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS-CoV2 pandemic (2009-2019).

Materials And Methods: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates.

Trends in all-cause and cause-specific mortality by BMI levels in England, 2004-2019: a population-based primary care records study.

Background: In the UK, obesity rates are rising concurrently with declining mortality rates. Yet, there is limited research on the shifts of mortality trends and the impact of obesity-related mortality. In this study, we examine mortality trends and the cause-specific proportional composition of deaths by body mass index.

Can the introduction of a 12-lead ECG help reduce mortality in those presenting with foot ulceration to multidisciplinary diabetic foot clinics? An observational evaluation of a real-world implementation pilot in England.

Aims/hypothesis: The risk of dying within 2 years of presentation with diabetic foot ulceration is over six times the risk of amputation, with CVD the major contributor. Using an observational evaluation of a real-world implementation pilot, we aimed to assess whether for those presenting with diabetic foot ulceration in England, introducing a 12-lead ECG into routine care followed by appropriate clinical action was associated with reduced mortality.

Methods: Between July 2014 and December 2017, ten multidisciplinary diabetic foot services in England participated in a pilot project introducing 12-lead ECGs for new attendees with foot ulceration.

A cluster randomised controlled trial, process and economic evaluation of quality improvement collaboratives aligned to a national audit to improve the care for people with diabetes (EQUIPD): study protocol.

Background: People with type 1 diabetes and raised glucose levels are at greater risk of retinopathy, nephropathy, neuropathy, cardiovascular disease, sexual health problems and foot disease. The UK National Institute for Health and Care Excellence (NICE) recommends continuous subcutaneous 'insulin pump' therapy for people with type 1 diabetes whose HbA1c is above 69 mmol/mol. Insulin pump use can improve quality of life, cut cardiovascular risk and increase treatment satisfaction.

National Trends in Hyperglycemia and Diabetic Ketoacidosis in Children, Adolescents, and Young Adults With Type 1 Diabetes: A Challenge Due to Age or Stage of Development, or Is New Thinking About Service Provision Needed?

Objective: Adolescence is associated with high-risk hyperglycemia. This study examines the phenomenon in a life course context.

Research Design And Methods: A total of 93,125 people with type 1 diabetes aged 5 to 30 years were identified from the National Diabetes Audit and/or the National Paediatric Diabetes Audit for England and Wales for 2017/2018-2019/2020.

Comparative Incidence of Diabetes Following Hospital Admission for COVID-19 and Pneumonia: A Cohort Study.

Objective: The incidence of diabetes may be elevated following coronavirus disease 2019 (COVID-19), but it is unclear whether this is specific to severe acute respiratory syndrome coronavirus 2 infection, associated with shared risk factors for severe COVID-19 and diabetes, and/or a generic risk following illness.

Research Design And Methods: People admitted to the hospital for COVID-19 and/or pneumonia between 1 April 2020 and 31 August 2020 in England were linked with the National Diabetes Audit to identify incident diabetes after discharge up to 31 March 2021. Comparator cohorts admitted with pneumonia over the same dates in 2017, 2018, and 2019 were followed until 31 March 2018, 31 March 2019, and 31 March 2020, respectively.

Care processes in people in remission from type 2 diabetes: A cohort study using the National Diabetes Audit.

Aims: People with type 2 diabetes can enter remission but may relapse or develop legacy complications. This analysis assesses whether people with remission from type 2 diabetes continue receiving annual care processes recommended in national guidelines and the potential impacts of formal recognition of remission.

Methods: People with type 2 diabetes with and without formal recognition (diagnostic code) of remission, and with and without evidence of remission (HbA  < 48 mmol/mol without prescription for glucose-lowering drugs in preceding 26 weeks), included in the 2018/19 National Diabetes Audit (NDA) for England and Wales were followed up to identify care processes received between 1 January 2019 and 31 March 2020.

Impact of case-mix adjustment on observed variation in the healing of diabetic foot ulcers at 12 weeks using data from the National Diabetes Foot Care Audit of England and Wales: A cohort study.

Aim: This cohort study investigates the extent to which variation in ulcer healing between services can be explained by demographic and clinical characteristics.

Methods: The National Diabetes Foot Care Audit collated data on people with diabetic foot ulcers presenting to specialist services in England and Wales between July 2014 and March 2018. Logistic regression models were created to describe associations between risk factors and a person being alive and ulcer-free 12 weeks from presentation, and to investigate whether variation between 120 participating services persisted after risk factor adjustment.

Characteristics and care of young people with type 2 diabetes included in the national diabetes audit datasets for England.

Introduction: We report contemporary age-related prevalence, characteristics and care of children and young people with type 2 diabetes in England.

Methods: Individuals with a recorded diagnosis of type 2 diabetes between January 2019 and March 2020 were identified from a whole population register. Age, sex, ethnicity, deprivation quintile, weight, HbA and receipt of the nine National Institute for Health & Care Excellence (NICE) recommended annual care processes were extracted from electronic clinical records and analysed by pre-specified age bands.

Associations between reductions in routine care delivery and non-COVID-19-related mortality in people with diabetes in England during the COVID-19 pandemic: a population-based parallel cohort study.

Background: The Office for Health Improvement and Disparities, part of the UK Government Department of Health and Social Care, highlighted an emerging signal of increased non-COVID-19-related deaths in England between July and October, 2021, with a potentially disproportionate higher increase in people with diabetes. We aimed to substantiate and quantify this apparent excess mortality, and to investigate the association between diabetes routine care delivery and non-COVID-19-related-mortality in people with diabetes before and after the onset of the pandemic.

Methods: In this population-based parallel cohort study, we used the National Diabetes Audit (NDA) to identify people with diabetes in England.

How Valley-Orbit States in Silicon Quantum Dots Probe Quantum Well Interfaces.

The energies of valley-orbit states in silicon quantum dots are determined by an as yet poorly understood interplay between interface roughness, orbital confinement, and electron interactions. Here, we report measurements of one- and two-electron valley-orbit state energies as the dot potential is modified by changing gate voltages, and we calculate these same energies using full configuration interaction calculations. The results enable an understanding of the interplay between the physical contributions and enable a new probe of the quantum well interface.

Incidence and Characteristics of Remission of Type 2 Diabetes in England: A Cohort Study Using the National Diabetes Audit.

Objective: To assess the incidence of remission of type 2 diabetes in routine care settings.

Research Design And Methods: People with type 2 diabetes (HbA1c ≥48 mmol/mol [6.5%] or <48 mmol/mol [6.

Alanine-scanning mutagenesis of protein mannosyl-transferase from reveals strong activity-stability correlation.

In , protein O-mannosyl transferase (Pmt)-mediated protein O-glycosylation has an important role in cell envelope physiology. In defective Pmt leads to increased susceptibility to cell wall-targeting antibiotics, including vancomycin and β-lactams, and resistance to phage ϕC31. The aim of this study was to gain a deeper understanding of the structure and function of Pmt.

Coherent Control and Spectroscopy of a Semiconductor Quantum Dot Wigner Molecule.

Semiconductor quantum dots containing more than one electron have found wide application in qubits, where they enable readout and enhance polarizability. However, coherent control in such dots has typically been restricted to only the lowest two levels, and such control in the strongly interacting regime has not been realized. Here we report quantum control of eight different transitions in a silicon-based quantum dot.

Completion of annual diabetes care processes and mortality: A cohort study using the National Diabetes Audit for England and Wales.

Aim: To conduct an analysis to assess whether the completion of recommended diabetes care processes (glycated haemoglobin [HbA1c], creatinine, cholesterol, blood pressure, body mass index [BMI], smoking habit, urinary albumin, retinal and foot examinations) at least annually is associated with mortality.

Materials And Methods: A cohort from the National Diabetes Audit of England and Wales comprising 179 105 people with type 1 and 1 397 790 people with type 2 diabetes, aged 17 to 99 years on January 1, 2009, diagnosed before January 1, 2009 and alive on April 1, 2013 was followed to December 31, 2019. Cox proportional hazards models adjusting for demographic characteristics, smoking, HbA1c, blood pressure, serum cholesterol, BMI, duration of diagnosis, estimated glomerular filtration rate, prior myocardial infarction, stroke, heart failure, respiratory disease and cancer, were used to investigate whether care processes recorded January 1, 2009 to March 31, 2010 were associated with subsequent mortality.

Cohort profile: National Diabetes Audit for England and Wales.

Unlabelled: The National Diabetes Audit (NDA) collates and analyses data on the quality and variation in clinical care and outcomes for people with diabetes. It also provides opportunities to assess trends, determinants, and outcomes of diabetes to help guide clinical and public health priorities.

Cohort: Between 1 January 2003 and 31 March 2020, a total of 5,280,885 people diagnosed with diabetes were included in at least one NDA data collection.

Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England.

Background: In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes.

Fabrication process and failure analysis for robust quantum dots in silicon.

We present an improved fabrication process for overlapping aluminum gate quantum dot devices on Si/SiGe heterostructures that incorporates low-temperature inter-gate oxidation, thermal annealing of gate oxide, on-chip electrostatic discharge (ESD) protection and an optimized interconnect process for thermal budget considerations. This process reduces gate-to-gate leakage, damage from ESD, dewetting of aluminum and formation of undesired alloys in device interconnects. Additionally, cross-sectional scanning transmission electron microscopy (STEM) images elucidate gate electrode morphology in the active region as device geometry is varied.

Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study.

Background: Although diabetes has been associated with COVID-19-related mortality, the absolute and relative risks for type 1 and type 2 diabetes are unknown. We assessed the independent effects of diabetes status, by type, on in-hospital death in England in patients with COVID-19 during the period from March 1 to May 11, 2020.

Methods: We did a whole-population study assessing risks of in-hospital death with COVID-19 between March 1 and May 11, 2020.

Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.

Background: Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes.

Methods: We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England.