Evaluating a novel cervical orthosis, the Sheffield Support Snood, in patients with amyotrophic lateral sclerosis/motor neuron disease with neck weakness

Current practice and guidelines recommend the use of neck orthoses for people with amyotrophic lateral sclerosis (ALS) to compensate for neck weakness and to provide surrogate neck control. However, available options are frequently described by patients as restrictive and unsuitable and there was a need for a new device that addressed the needs of people with ALS. This project utilized a co-design process to develop a new neck orthosis that was more flexible yet supportive. Following development of a prototype device, a mixed methods cohort study was undertaken with patients and carers, in order to evaluate the new orthosis. Twenty-six patients were recruited to the study, with 20 of these completing all phases of data collection. Participants described the impact of neck weakness on their life and limitations of existing supports. Evaluation of the new orthosis identified key beneficial features: notably, increased support while providing a greater range of movement, flexibility of use, and improved appearance and comfort. In conclusion, the results of this evaluation highlight the value of this alternative option for people with ALS, and potentially other patient groups who require a neck orthosis

Band gap behavior of optimal one-dimensional composite structures with an additive manufactured stiffener

In this work, the banded behaviour of composite one-dimensional structures with an additive manufactured stiffener is examined. A finite element method is used to calculate the stiffness, mass and damping matrices, and periodic structure theory is used to obtain the wave propagation of one-dimensional structures. A multi-disciplinary design optimisation scheme is developed to achieve optimal banded behaviour and structural characteristics of the structures under investigation. Having acquired the optimal solution of the case study, a representative specimen is manufactured using a carbon fibre cured plate and additive manufactured nylon-based material structure. Experimental measurements of the dynamic performance of the hybrid composite structure are conducted using a laser vibrometer and electrodynamic shaker setup to validate the finite element model

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Handbook for preservation of local railroad service. Final report

Throughout the United States, there is an accelerating abandonment of redundant and/or unprofitable light-density railroad lines. This abandonment can be economically harmful to both the shippers and the communities that were previously served. Although greater dependence upon truck transportation is a viable alternative in many cases, other situations indicate that the greatest priority should be attached to preserving some form of local railroad service. The objective of this research was to develop a handbook to assist shippers, local and state governments, and rail planners when their Class I rail service is scheduled for abandonment. Two major options are detailed in the handbook. The first regards innovative procedures which may be used by local groups in attempting to preserve service by the existing Class I carrier. The second approach considers the alternative of operating the particular line as an independent railroad

Behavioural complexity in Eurasian Neanderthal populations: A chronological examination of the archaeological evidence

Whether Neanderthals were capable of behaviours commonly held to be the exclusive preserve of modern humans - such as abstract thought, language, forward planning, art, reverence of the dead, complex technology, etc. - has remained a fundamental question in human evolutionary studies since their discovery more than a hundred years ago. A lack of quantitative data on Neanderthal symbolism and complex behaviour is a key obstacle to the resolution of this question, with temporal analyses usually confined to single regions or short time periods. Here we present an approach to the issue of symbolism and complex behaviours among Neanderthals that examines the frequency of key proxies for symbolic and complex behaviours through time, including burials, modified raw materials, use of pigments, use of composite technology and body modification. Our analysis demonstrates that the number and diversity of complex Neanderthal behaviours increases between 160,000 and 40,000 years ago. Whether this pattern derives from preservation factors, the evolution of cognitive and behavioural complexity cumulative learning, or population size is discussed. We take the view that it is not the apparent sophistication of a single specific item, nor the presence or absence of particular types in the archaeological record that is important. Instead, we believe that it is the overall abundance of artefacts and features indicative of complex behaviours within the Neanderthal archaeological record as a whole that should provide the mark of Neanderthal capabilities and cultural evolutionary potential

Photon acceleration by laser produced wakefields on Astra

This chapter looks at photon acceleration by laser produced wakefields on Astr