Systematic Approach to Parametrization of Disaccharides for the Martini 3 Coarse-Grained Force Field.

Sugars are ubiquitous in biology; they occur in all kingdoms of life. Despite their prevalence, they have often been somewhat neglected in studies of structure-dynamics-function relationships of macromolecules to which they are attached, with the exception of nucleic acids. This is largely due to the inherent difficulties of not only studying the conformational dynamics of sugars using experimental methods but indeed also resolving their static structures.

How did investigations into spontaneous human combustion influence alcohol medicine? An examination of the medical and literary discussions that brought the two together.

Background And Aims: The presence of sections or chapters on spontaneous human combustion in more than half of the key texts in English on the action of alcohol on the body and mind in the first half of the nineteenth century demonstrates the seriousness with which it was considered. We aimed to chart discussions about the links between spontaneous human combustion and spirit drinking in medical texts and representations in fiction through three key chronological periods from 1804 to 1900.

Methods: A contextual analysis using eighteenth- and nineteenth-century historical, literary and medical sources to chart and reflect on public and medical discourses.

Molecular Crowding Alters the Interactions of Polymyxin Lipopeptides within the Periplasm of : Insights from Molecular Dynamics.

The cell envelope of Gram-negative bacteria is a crowded tripartite architecture that separates the cell interior from the external environment. Two membranes encapsulate the aqueous periplasm, which contains the cell wall. Little is known about the mechanisms via which antimicrobial peptides move through the periplasm from the outer membrane to their site of action, the inner membrane.

Computational microbiology of bacteria: Advancements in molecular dynamics simulations.

Microbiology is traditionally considered within the context of wet laboratory methodologies. Computational techniques have a great potential to contribute to microbiology. Here, we describe our loose definition of "computational microbiology" and provide a short survey focused on molecular dynamics simulations of bacterial systems that fall within this definition.

Building lean improvement sckills at scale: an evaluation of a massive open online course in the English NHS.

Background: Internationally, healthcare systems face challenges from population demographics and rising care costs. Systematic methods of quality improvement (QI) are considered key to delivering needed transformation and change. Large-scale training in QI skills is required.

Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders.

Introduction: While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits.

Methods: We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573).

The impact of alcohol minimum unit pricing on people with experience of homelessness: Qualitative study.

Background: Alcohol Minimum Unit Pricing (MUP) was introduced in Scotland in May 2018. Existing evidence suggests MUP can reduce alcohol consumption in the general population, but there is little research about its impact on vulnerable groups. This qualitative study explored experiences of MUP among people with experience of homelessness.

Alcohol minimum unit pricing and people experiencing homelessness: A qualitative study of stakeholders' perspectives and experiences.

Introduction: Minimum unit pricing (MUP) may reduce harmful drinking in the general population, but there is little evidence regarding its impact on marginalised groups. Our study is the first to explore the perceptions of MUP among stakeholders working with people experiencing homelessness following its introduction in Scotland in May 2018.

Methods: Qualitative semi-structured interviews were conducted with 41 professional stakeholders from statutory and third sector organisations across Scotland.

Recovering staff, recovering services: massive-online support for recovering a paediatric service using Lean and compassionate communication.

The COVID-19 pandemic has infected tens of millions worldwide. Healthcare systems have been stretched caring for the most seriously ill and healthcare workers have struggled to maintain non-COVID services leading to backlogs.Strategies proposed to support the recovery of backlogs include additional administration support; waiting list data validation; enhanced patient communication; and use of systematic improvement methods to make rapid incremental improvements.

Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial.

Background: Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock.

Methods: Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK.

Mass production methods for mass vaccination: improving flow and operational performance in a COVID-19 mass vaccination centre using Lean.

The COVID-19 pandemic has infected tens of millions of people worldwide causing many deaths. Healthcare systems have been stretched caring for the most seriously ill and lockdown measures to interrupt COVID-19 transmission have had adverse economic and societal impacts. Large-scale population vaccination is seen as the solution.

Operations management on the front line of COVID-19 vaccination: building capability at scale via technology-enhanced learning.

The globe is gripped by the COVID-19 pandemic. Mass population vaccination is seen as the solution. As vaccines become available, governments aim to deploy them as rapidly as possible.

Driving quality improvement with a massive open online course (MOOC).

Background: Quality improvement (QI) is a priority for national regulatory bodies in health and care in the UK. However, many health and care staff do not know where to go for support in gaining the required skills and knowledge in QI. This paper reviews Improvement Fundamentals, a massive open online course (MOOC), designed to address this gap, run by an improvement team in the national regulatory body.

The hitchhiker's guide to the periplasm: Unexpected molecular interactions of polymyxin B1 in E. coli.

The periplasm of Gram-negative bacteria is a complex, highly crowded molecular environment. Little is known about how antibiotics move across the periplasm and the interactions they experience. Here, atomistic molecular dynamics simulations are used to study the antibiotic polymyxin B1 within models of the periplasm, which are crowded to different extents.

CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides.

Hydrogen mass repartitioning (HMR) that permits time steps of all-atom molecular dynamics simulation up to 4 fs by increasing the mass of hydrogen atoms has been used in protein and phospholipid bilayers simulations to improve conformational sampling. Molecular simulation input generation via CHARMM-GUI now supports HMR for diverse simulation programs. In addition, considering ambiguous pH at the bacterial outer membrane surface, different protonation states, either -2e or -1e, of phosphate groups in lipopolysaccharides (LPS) are also supported in CHARMM-GUI .

Capability building for large-scale transformational change: learning from an evaluation of a national programme.

Background: The Long Term Plan presents an ambitious vision for England's National Health Service which will require a sustained programme of transformational change. The Virtual Academy of Large-Scale Change (VALSC) was developed to build capability in health and care system teams involved in transformation or redesign programmes.

Methods: To evaluate the VALSC, quantitative and qualitative data were collected and reviewed against the Kirkpatrick model.

The influence of regression models on genome-wide association studies of alcohol dependence: a comparison of binary and quantitative analyses.

Introduction: Genome-wide association studies (GWAS) of alcohol dependence syndrome (ADS) offer a platform to detect genetic risk loci. However, the majority of the ADS GWAS undertaken, to date, have utilized a case-control design and have failed to identify consistently replicable loci with the exception of protective variants within the alcohol metabolizing genes, notably ADH1B. The ADS phenotype shows considerable variability which means that the use of quantitative variables as a proxy for the severity of ADS has the potential to facilitate identification of risk loci by increasing statistical power.

The importance of anatomical reduction in the functional outcome of open ankle fractures.

Introduction: Whilst closed ankle fracture injuries are common, well characterized and have treatment guidelines derived from the literature, open ankle fractures are rare and are not well studied. The few studies that exist are from the developed First World and these well resourced circumstances are not available in most parts of the world. The purpose of this prospective study was to assess the functional outcomes of open ankle fractures and the factors associated with their outcome in an adult population in rural South Africa.

Adapting Lean methods to facilitate stakeholder engagement and co-design in healthcare.

Quality improvement approaches drawn from industry can go beyond traditional concepts of value and deliver improvements in healthcare services, argue

Baclofen and the Alcohol Withdrawal Syndrome-A Short Review.

The Alcohol Withdrawal Syndrome (AWS), which may occur with or without delirium, is a frequent consequence of sudden alcohol cessation in patients with moderate to severe Alcohol Dependence Syndrome (ADS). Withdrawal as a result of habituation to alcohol is part of the definition of the Alcohol Dependence Syndrome (ICD10). Since the recognition of Delirium Tremens, in the early nineteenth century, the management of the syndrome, an acute medical emergency, has proven controversial.

Electric-Field-Driven Translocation of ssDNA through Hydrophobic Nanopores.

The accurate sequencing of DNA using nanopores requires control over the speed of DNA translocation through the pores and also of the DNA conformation. Our studies show that ssDNA translocates through hourglass-shaped pores with hydrophobic constriction regions when an electric field is applied. The constriction provides a barrier to translocation and thereby slows down DNA movement through the pore compared with pores without the constriction.