Background: It would be clinically useful to prospectively identify the risk of disease progression in chronic myeloid leukaemia (CML). Overexpression of cancerous inhibitor of protein phosphatase 2A (PP2A) (CIP2A) protein is an adverse prognostic indicator in many cancers. Methods: We examined CIP2A protein levels in diagnostic samples from the SPIRIT2 trial in 172 unselected patients, of whom 90 received imatinib and 82 dasatinib as first-line treatment. Results: High CIP2A levels correlated with inferior progression-free survival (p = 0.04) and with worse freedom from progression (p = 0.03), and these effects were confined to dasatinib recipients. High CIP2A levels were associated with a six-fold higher five-year treatment failure rate than low CIP2A levels (41% vs. 7.5%; p = 0.0002), in both imatinib (45% vs. 11%; p = 0.02) and dasatinib recipients (36% vs. 4%; p = 0.007). Imatinib recipients with low CIP2A levels had a greater risk of treatment failure (p = 0.0008). CIP2A levels were independent of Sokal, Hasford, EUTOS (EUropean Treatment and Outcome Study), or EUTOS long-term survival scores (ELTS) or the presence of major route cytogenetic abnormalities. No association was seen between CIP2A levels and time to molecular response or the levels of the CIP2A-related proteins PP2A, SET, SET binding protein 1 (SETBP1), or AKT. Conclusions: These data confirm that high diagnostic CIP2A levels correlate with subsequent disease progression and treatment failure. CIP2A is a simple diagnostic biomarker that may be useful in planning treatment strategies.

In this work, water hyacinths, bagasse and rice straw were valorized to produce an innovative biopolymer. Serial steps of extraction, bleaching and conversion of cellulose to be carboxymethylcellulose (CMC) as well as the last steps of blending and molding were performed. The CMC was mixed with tapioca starch solution by a ratio of 9:18, and a plastic sizer of glycerol was varied at 2%, 4% and 6% by volume. In addition, bioplastic sheets were further determined in their properties and biodegradation. The results revealed that bioplastics with 6% glycerol showed a high moisture content of 23% and water solubility was increased by about 47.94% over 24 h. The effect of temperature on bioplastic stability was found in the ranges of 146.28–169.25 °C. Furthermore, bioplastic sheets with 2% glycerol could maintain their shape. Moreover, for texture analysis, the highest elastic texture in the range of 33.74–38.68% with 6% glycerol was used. Moreover, bioplastics were then tested for their biodegradation by landfill method. Under natural conditions, they degraded at about 10.75% by weight over 24 h after burying in 10 cm soil depth. After 144 h, bioplastics were completely decomposed. Successfully, the application of water, weed and agricultural wastes as raw materials to produce innovative bioplastic showed maximum benefits for an environmentally friendly product, which could also be a guideline for an alternative to replace synthetic plastics derived from petroleum.

Serving military personnel and veterans have been identified to have a high prevalence of mental health disorders. Despite this, only a significantly small number seek mental healthcare. With the UK beginning to invest further support to the armed forces community, identification of barriers and facilitators of help-seeking behaviour is needed. Corresponding literature search was conducted in PsycINFO, PsycArticles, Medline, Web of Science and EBSCO. Articles which discussed barriers and facilitators of seeking help for mental health concerns in the veteran population were included. Those which discussed serving personnel or physical problems were not included within this review. A total of 26 papers were analysed. A number of barriers and facilitators of help-seeking for a mental health issue within the veteran population were identified. Barriers included stigma, military culture of stoicism and self-reliance, as well as deployment characteristics of combat exposure and different warzone deployments. Health service difficulties such as access and lack of understanding by civilian staff were also identified. Facilitators to help combat these barriers included a campaign to dispel the stigma, including involvement of veterans and training of military personnel, as well as more accessibility and understanding from healthcare staff. While some barriers and facilitators have been identified, much of this research has been conducted within the USA and on male veterans and lacks longitudinal evidence. Further research is needed within the context of other nations and female veterans and to further indicate the facilitators of help-seeking among veterans. [Abstract copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.]

Integrin receptors are transmembrane proteins that bind to the extracellular matrix (ECM). In most animal cell types integrins cluster together with adaptor proteins at focal adhesions that sense and respond to external mechanical signals. In the central nervous system (CNS), ECM proteins are sparsely distributed, the tissue is comparatively soft and neurons do not form focal adhesions. Thus, how neurons sense tissue stiffness is currently poorly understood. Here, we found that integrins and the integrin-associated proteins talin and focal adhesion kinase (FAK) are required for the outgrowth of neuronal processes. Vinculin, however, whilst not required for neurite outgrowth was a key regulator of integrin-mediated mechanosensing of neurons. During growth, growth cones of axons of CNS derived cells exerted dynamic stresses of around 10-12 Pa on their environment, and axons grew significantly longer on soft (0.4 kPa) compared to stiff (8 kPa) substrates. Depletion of vinculin blocked this ability of growth cones to distinguish between soft and stiff substrates. These data suggest that vinculin in neurons acts as a key mechanosensor, involved in the regulation of growth cone motility. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]

The UK average survival rate from out of hospital cardiac arrest (OHCA) is 8.6%, which is significantly lower than in comparable countries where survival rates can exceed 20%. A cardiac arrest victim is two to four times more likely to survive OHCA with bystander cardiopulmonary resuscitation (CPR). Mandatory teaching of CPR in schools is an effective way, endorsed by the World Health Organization, to train the entire population and improve the bystander CPR rate. Despite this, as with other UK home nations, there is significant variation in provision of CPR training within schools in Wales. Virtual reality (VR) technology offers an accessible, immersive way to teach CPR skills to schoolchildren. Computer scientists at the University of Chester and the Welsh Ambulance Services NHS Trust developed Virtual Cardio Pulmonary Resuscitation (VCPR), which can be used to teach children CPR skills. There were three stages: identifying requirements and specifications; development of a prototype; and management—development of software, further funding and exploring opportunities for commercialisation.

<h4>Background</h4>The number of individuals with a visual impairment in the UK was estimated a few years ago to be around 1.8 million. People can be visually impaired from birth, childhood, early adulthood or later in life. Those with visual impairment are subject to health inequities and increased risk for patient safety incidents in comparison to the general population. They are also known to be at an increased risk of experiencing medication errors compared to those without visual impairment. In view of this, this review aims to understand the issues of medication safety for VI people.<h4>Methods/design</h4>Four electronic bibliographic databases will be searched: MEDLINE, Embase, PsycInfo and CINAHL. Our search strategy will include search combinations of two key blocks of terms. Studies will not be excluded based on design. Included studies will be empirical studies. They will include studies that relate to both medication safety and visual impairment. Two reviewers (SG and LR) will screen all the titles and abstracts. SG, LR, RM, SCS and PL will perform study selection and data extraction using standard forms. Disagreements will be resolved through discussion or third party adjudication. Data to be collected will include study characteristics (year, objective, research method, setting, country), participant characteristics (number, age, gender, diagnoses), medication safety incident type and characteristics.<h4>Discussion</h4>The review will summarise the literature relating to medication safety and visual impairment.

Internal migration has significant impacts on the population structure, public services, economic and social development of local areas. In this research, we adopted the theory and methods of complex network analysis to visualise the internal migration flows across local authorities in England and Wales. The graphic prominently highlights two spatial and geographic characteristics of population mobility in England and Wales: a large proportion of internal migration is associated with clusters of neighbouring or nearby local authorities, and the most urban authorities, such as London and other major metropolitan cities, have net outward internal migration (i.e., more people moving out than in).

Vitamin B (cobalamin) is an essential cofactor for two metabolic pathways. It is obtained principally from food of animal origin. Cobalamin becomes bioavailable through a series of steps pertaining to its release from dietary protein, intrinsic factor-mediated absorption, haptocorrin or transcobalamin-mediated transport, cellular uptake, and two enzymatic conversions ( methionine synthase and methylmalonyl-CoA-mutase) into cofactor forms: methylcobalamin and adenosylcobalamin. Vitamin B deficiency can masquerade as a multitude of illnesses, presenting different perspectives from the point of view of the hematologist, neurologist, gastroenterologist, general physician, or dietician. Increased physician vigilance and heightened patient awareness often account for its early presentation, and testing sometimes occurs during a phase of vitamin B insufficiency before the main onset of the disease. The chosen test often depends on its availability rather than on the diagnostic performance and sensitivity to irrelevant factors interfering with vitamin B markers. Although serum B is still the most commonly used and widely available test, diagnostics by holotranscobalamin, serum methylmalonic acid, and plasma homocysteine measurements have grown in the last several years in routine practice. The lack of a robust absorption test, coupled with compromised sensitivity and specificity of other tests (intrinsic factor and gastric parietal cell antibodies), hinders determination of the cause for depleted B status. This can lead to incorrect supplementation regimes and uncertainty regarding later treatment. This review discusses currently available knowledge on vitamin B , informs the reader about the pitfalls of tests for assessing its deficiency, reviews B status in various populations at different disease stages, and provides recommendations for interpretation, treatment, and associated risks. Future directions for diagnostics of B status and health interventions are also discussed.

The prospect of being able to move through security without the inconvenience of separating liquids from bags is an exciting one for passengers, and there are important operational benefits for airports as well. Here, two terahertz (THz) systems, 100 GHz sub-THz line scanner and attenuation total reflection-based THz time domain spectroscopy (TDS), have been used to demonstrate the capability of identifying different liquid samples. Liquid samples’ THz complex permittivities are measured and their differences have contributed to the variation of 100 GHz 2D images of volatile liquids with different volumes inside of cannister bottles. The acquired attenuation images at 100 GHz can easily be used to distinguish highly absorbed liquids (Water, Ethanol, Fuel Treatment Chemicals) and low loss liquids (Petrol, Diesel, Kerosene and Universal Bottle Cleaner). The results give a promising feasibility for mm-wave imager and THz spectroscopy to efficiently identify different volatile liquids.