The effect of a home-based, gamified stability skills intervention on 4-5-year-old children's physical and cognitive outcomes: A pilot study.

BACKGROUND: Stability skills (e.g., static/dynamic balance) are a precursor for other movement skill development (e.g., jumping, catching). However, young children consistently demonstrate low stability and movement skill ability. There is therefore a need to develop effective strategies to improve stability skills in early childhood. AIM: To pilot the effect of a home-based gamified stability skills intervention on 4-5-year-old children's physical skills, self-perceptions and cognitions. METHODS: One-hundred-and-eleven 4-5-year-old children participated from three schools. Two schools were allocated into the intervention group (n = 66 children, 33 boys) and one to the control group (n = 45 children, 25 boys). Stability, fundamental movement skills, perceived motor competence, and cognition were assessed at baseline and at post-intervention. The intervention group was given a booklet detailing the 12-week gamified stability skill intervention. The control group participated in their usual weekly activities. RESULTS: A series of ANCOVAs controlling for baseline values demonstrated significantly higher stability skills (F(1,93) = 24.79, p < 0.001, partial η2 = 0.212), fundamental movement skills (F(1,94) = 15.5, p = < 0.001, partial η2 = 0.139), perceived motor competence (F(1,96) = 5.48, p = 0.021, partial η2 = 0.054) and cognition (F(1,96) = 15.5, p = < 0.001, partial η2 = 0.139) at post-test for the intervention versus control groups. DISCUSSION: This study demonstrates that a home-based, gamified, stability skills intervention enhances stability skills, fundamental movement skills, perceived motor competence and cognition in children aged 4-5-years old.

Immunogenic cell death in colorectal cancer: a review of mechanisms and clinical utility.

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide. Despite several clinical advances the survival of patients with advanced colorectal cancer remains limited, demanding newer approaches. The immune system plays a central role in cancer development, propagation, and treatment response. Within the bowel, the colorectal mucosa is a key barrier and site of immune regulation that is generally immunosuppressive. Nonetheless, within this tumour microenvironment, it is evident that anti-neoplastic treatments which cause direct cytotoxic and cytostatic effects may also induce immunogenic cell death (ICD), a form of regulated cell death that leads to an anti-tumour immune response. Therefore, novel ICD inducers and molecular biomarkers of ICD action are urgently needed to advance treatment options for advanced CRC. This article reviews our knowledge of ICD in CRC.

'Getting control of Corona takes many angles': COVID-19 vaccine knowledge, attitudes and beliefs among refugee/immigrant/migrant communities in four US cities.

The objectives of the study were to (i) document refugee, immigrant and migrant (RIM) communities' knowledge, attitudes and beliefs (KABs) related to the Coronavirus disease (COVID-19) vaccine and (ii) identify best practices for developing and disseminating culturally and linguistically responsive health messaging addressing those KABs. Thirteen online focus groups (OFGs) in 10 languages were conducted. Each OFG was conducted in the participants' native language. OFGs were recorded, transcribed, translated and uploaded to qualitative software for coding. A thematic analysis was conducted. Results suggest that while there was some variation between different language groups (e.g. whether religious leaders were seen as trusted sources of information about COVID), there were also important commonalities. Most language groups (i) alluded to hearing about or having gaps in knowledge about COVID-19/the COVID-19 vaccine, (ii) reported hearing negative or conflicting stories about the vaccine and (iii) shared concerns about the negative side effects of the vaccine. There continues to be a need for health messaging in RIM communities that is culturally and linguistically concordant and follows health literacy guidelines. Message content about the COVID-19 vaccine should focus on vaccine importance, effectiveness and safety, should be multimodal and should be primarily delivered by healthcare professionals and community members who have already been vaccinated.

Diamond-Like Carbon: A Surface for Extreme, High-Wear Environments.

In this study, we present an in-depth characterization of a diamond-like carbon (DLC) film, using a range of techniques to understand the structure and chemistry of the film both in the interior and particularly at the DLC/air surface and DLC/liquid interface. The DLC film is found to be a combination of sp2 and sp3 carbon, with significant oxygen present at the surface. The oxygen seems to be present as OH groups, making the DLC somewhat hydrophilic. Quartz-Crystal Microbalance (QCM) isotherms and complementary neutron reflectivity data indicate significant adsorption of a model additive, bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) surfactant, onto the DLC from water solutions and indicate the adsorbed film is a bilayer. This initial study of the structure and composition of a model surfactant is intended to give a clearer insight into how DLC and additives function as antiwear systems.

Ultra-low oxygen, liquid sample cell for in situ synchrotron-based small-wide angle scattering (SAXS-WAXS).

Here, we report the design and successful implementation of an ultra-low oxygen sample cell for use on the SAXS-WAXS (small-wide angle x-ray scattering) beamline I22 at DIAMOND. The rigorous exclusion of oxygen is found to require double jacketing with purge gas throughout the entire system, pipework, pumps, and the sample cell itself. This particularly includes a "double-window" arrangement at the sample location to accommodate the very tight geometrical restrictions of the sample position. The in situ cell design also requires the additional complexity of heating the sample/solution and real-time electrochemical measurements. We demonstrate the successful implementation of this arrangement with real-time in situ characterization of an iron foil corrosion evolving under the "sweet-scale environment," very anoxic conditions common, in particular, commercial situations. The formation of iron carbonate, siderite, rather than iron oxide, indicates that our system is oxygen free down very low levels (<35 ppb at 80 °C).

Hypertension in Adults: Initial Evaluation and Management.

Hypertension is a leading modifiable risk factor for cardiovascular disease and the most common chronic condition seen by family physicians. Treatment of hypertension reduces morbidity and mortality due to coronary artery disease, myocardial infarction, heart failure, stroke, and chronic kidney disease. The use of ambulatory and home blood pressure monitoring improves diagnostic accuracy. Assessment of adults with hypertension should focus on identifying complications of the condition and comorbid cardiovascular risk factors. Physicians should counsel all patients with elevated blood pressure about effective lifestyle interventions, including the Dietary Approaches to Stop Hypertension (DASH) diet, dietary sodium restriction, potassium enrichment, regular exercise, weight loss, and moderation of alcohol consumption. First-line antihypertensive medications include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and thiazide diuretics. Thresholds for pharmacologic intervention and blood pressure goals differ according to various guidelines. Evidence strongly supports reducing blood pressure to less than 140/90 mm Hg to reduce the risk of all-cause and cardiovascular mortality in adults with hypertension. Lowering blood pressure to less than 135/85 mm Hg may further reduce the risk of myocardial infarction. Clinical judgment and shared decision-making should guide treatment of patients with mild hypertension and older adults who may be more susceptible to adverse effects of antihypertensive medications and tight blood pressure control.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Lithium Intercalation into the Excitonic Insulator Candidate Ta2NiSe5.

A new reduced phase derived from the excitonic insulator candidate Ta2NiSe5 has been synthesized via the intercalation of lithium. LiTa2NiSe5 crystallizes in the orthorhombic space group Pmnb (no. 62) with lattice parameters a = 3.50247(3) Å, b = 13.4053(4) Å, c = 15.7396(2) Å, and Z = 4, with an increase of the unit cell volume by 5.44(1)% compared with Ta2NiSe5. Significant rearrangement of the Ta-Ni-Se layers is observed, in particular a very significant relative displacement of the layers compared to the parent phase, similar to that which occurs under hydrostatic pressure. Neutron powder diffraction experiments and computational analysis confirm that Li occupies a distorted triangular prismatic site formed by Se atoms of adjacent Ta2NiSe5 layers with an average Li-Se bond length of 2.724(2) Å. Li-NMR experiments show a single Li environment at ambient temperature. Intercalation suppresses the distortion to monoclinic symmetry that occurs in Ta2NiSe5 at 328 K and that is believed to be driven by the formation of an excitonic insulating state. Magnetometry data show that the reduced phase has a smaller net diamagnetic susceptibility than Ta2NiSe5 due to the enhancement of the temperature-independent Pauli paramagnetism caused by the increased density of states at the Fermi level evident also from the calculations, consistent with the injection of electrons during intercalation and formation of a metallic phase.

Detecting and characterizing special nuclear material for nuclear nonproliferation applications.

There is an urgent need for new, better instrumentation and techniques for detecting and characterizing special nuclear material (SNM), i.e., highly enriched uranium and plutonium. The development of improved instruments and techniques requires experiments performed with the SNM itself, which is of limited availability. This paper describes the findings of experiments performed at the National Criticality Experiments Research Center conducted using new instruments and techniques on unclassified, kg-quantity SNM objects. These experiments, performed in the framework of the Department of Energy, National Nuclear Security Administration Consortium for Monitoring, Technology, and Verification, focused on detecting, characterizing, and localizing SNM samples with masses ranging from 3.3 to 13.8 kg, including plutonium and highly enriched uranium using prototype detectors and techniques. The work demonstrates SNM detection and characterization using recently-developed prototype detection systems. Specifically, we present new results in passive detection and imaging of plutonium and uranium objects using gamma-ray and dual particle (fast neutron and gamma-ray) imaging. We also present a new analysis of the delayed neutron emissions during active interrogation of uranium using a neutron generator.

A Novel Study on the Role of Pressure on Surface Adsorption from Solutions.

In this work, we present experimental data on the behavior of model additives adsorbed at the solid/liquid interface as a function of pressure. We report that some additives adsorbed from non-aqueous solvents exhibit rather little variation with pressure, while others exhibit more significant changes. We also display the important pressure dependence of added water. This pressure dependence is relevant, indeed central to many commercially important situations where the adsorption of molecular species to the solid/liquid interface under high pressure is key, such as wind turbines, and this work should help in understanding how protective, anti-wear, or friction-reducing agents can persist (or not) under these extreme conditions. With a very significant gap in the fundamental understanding of the role of pressure on adsorption from solution phases, this important fundamental study provides a methodology to investigate the pressure dependence of these academically and commercially important systems. In the best case, one may even be able to predict which additives will lead to more adsorption under pressure and avoid those that may desorb.

Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.

AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Outcome of adalimumab monotherapy in paediatric non-infectious uveitis.

BACKGROUND: Adalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis. METHODS: Children with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data were collected at the initiation of adalimumab monotherapy and at three monthly intervals until the last visit. The primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy. RESULTS: Data was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis-associated uveitis was the most common underlying diagnosis. During the study period, 23 (82.14%) of the study subjects met the primary outcome. On Kaplan-Meier survival analysis 81.25% (95% CI; 60.6-91.7%) children maintained remission at 12 months on adalimumab monotherapy. CONCLUSION: Continuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate mofetil.

Potential of in-plant intramuscular fat predictions to enable sheep breeders to incorporate consumer preferences in breeding programmes.

The inclusion of eating quality traits in sheep genetic improvement programmes is desirable. Intramuscular fat (IMF) plays a key role in ensuring consumer satisfaction when eating lamb, but genetic progress for IMF is constrained by a lack of routine data collection. This study investigated the potential for IMF predictor traits to substitute for measured IMF in genetic improvement programmes. Carcass and predicted IMF (near-infrared estimated IMF and marbling score) data were available on 10,113 New Zealand lambs, 1678 of which also had measured chemical IMF on a slice of M. longissimus lumborum on which the predictions of IMF had been made. Genetic antagonisms were observed between carcass lean traits and IMF. The genetic correlation between the predictors and measured IMF approached one, indicating that predictors of IMF can be used in genetic improvement programmes. Through using selection indexes, simultaneous increases in IMF and the existing terminal selection index are possible, provided all traits are measured. This study highlights the importance and potential of predicted IMF to achieve genetic improvement in traits of importance to consumers.

Corrosion inhibitor distribution on abrasive-blasted steels.

HYPOTHESIS: Abrasive-blasted steel surfaces exhibit a complex, multi-substrate environment. Adsorption to contaminant substrates can reduce the amount of available corrosion inhibitor and decrease its efficiency. Knowledge of where inhibitors preferentially adsorb is required. EXPERIMENTS: The quantitative extent and strength of adsorption of the representative corrosion inhibitor benzotriazole (BTAH) from toluene to particular substrates is given, including corrections for solution self-association, and complemented by X-ray photoelectron spectroscopy (XPS), sum-frequency generation spectroscopy (SFG), and quartz crystal microbalance (QCM) measurements. FINDINGS: All substrates show adsorbed BTAH layers. Based on the adsorption strength, preferential adsorption is found to be in the order steel > iron oxide > calcium carbonate and garnet > silica - this is relevant when there is limited BTAH. However, with ample BTAH, the amounts adsorbed in the plateau regions of the isotherm are more relevant and the order is calcium carbonate and silica > iron oxide > garnet > steel. Although the contaminant substrates deplete the BTAH concentration, the steel should still have a complete monolayer of BTAH inhibitor. This work is part of a larger initiative developing novel methods of corrosion inhibitor delivery via the blasting process, to prevent corrosion between blasting and repainting.

Description and outcome of dogs with primary immune-mediated polyarthritis: 73 cases (2012-2017).

OBJECTIVES: To provide a description of primary idiopathic immune-mediated polyarthritis, including long-term outcome and relapse rates, for dogs starting treatment with corticosteroids alone or corticosteroids with a second immunosuppressant. MATERIALS AND METHODS: Medical records were reviewed between January 2012 and December 2017 to identify dogs diagnosed with primary immune-mediated polyarthritis. Data including signalment, clinicopathological findings, type and duration of treatment, relapse and outcome were recorded. RESULTS: Seventy-three dogs were included. Fifty-four dogs were started on corticosteroid monotherapy (an additional immunosuppressant was introduced later in 27/54 dogs) and 19 dogs were treated with multi-modal immunosuppression from the outset. Ninety-five percent (69/73) of dogs responded favourably to therapy although death was attributed to immune-mediated polyarthritis in 19% (14/73) of dogs. Relapse of clinical signs was reported in 53% (39/73) dogs (31/39 while on treatment), with multiple relapses observed in 17 dogs. Complete cure (permanent withdrawal of immunosuppressive medication) was achieved in 46 dogs (63%). Overall, 81% of dogs had a well-managed disease for an extended timeframe (≥1131 days). Fourteen of 19 (74%) dogs that started treatment with multi-modal immunosuppression and 32 of 54 (59%) started on corticosteroids alone achieved a complete cure. CLINICAL SIGNIFICANCE: This study provides extended follow-up information for a large cohort of dogs with primary immune-mediated polyarthritis. Immunosuppressive therapy was discontinued in the majority of dogs but disease-associated mortality remains high.

Pestilence, Plague and Pandemics: A Troubled History.

Humankind has lived with the danger of endemic, epidemic and pandemic disease for thousands of years. The effects of these outbreaks have often devastated human populations. Sixteen pandemic events causing an estimated 147 million deaths have occurred since the eighth century, The Black Death and the influenza pandemic of 1918-1920 probably having the greatest impact. Animal populations, both wild and domestic, have similarly suffered devastating outbreaks of disease which, on occasions, have translated into serious effects on human health. The deliberate or accidental introduction of animals into virgin areas has given rise to unforeseen disease events occasionally leading to extinction. Similarly, human intent or negligence and the vagaries of nature itself has resulted in ill health and loss of life. This paper describes the history of pandemics, epidemics and disasters, and the attempts to bring them under control.

Cost of treating metastatic colorectal cancer: a systematic review.

OBJECTIVE: The cost of treating metastatic colorectal cancer places a significant economic burden on individuals, populations, and health care. However, there is a paucity of information on the costs of the contemporary management of metastatic colorectal cancer. This systematic review aims to review the literature to estimate the direct cost of treating metastatic colorectal cancer. STUDY DESIGN: Systematic review. METHODS: MEDLINE, Embase, Web of Science, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database Guide, EconLit, and grey literature from the 1st of January 2000 to the 1st of February 2020 were all searched for studies reporting the direct costs of treating metastatic colorectal cancer. The methodological quality of the included studies was assessed using the Evers' Consensus on Health Economic Criteria checklist. RESULTS: In total, 39,489 records were retrieved, and 29 studies were included. Costs of treating metastatic colorectal cancer varied because of the heterogeneity of treatment. Studies reported average costs ranged from $12,346 to $293,461. Studies that included the cost of systemic therapy reported an estimated cost of almost $300,000. CONCLUSION: The existing evidence indicates that the cost of treating metastatic colorectal cancer places a significant economic burden on healthcare systems despite differences in methodology and treatment heterogeneity. Future research needs to define the cost components of treating metastatic colorectal cancer to improve comparability and examine the relationship between spending, overall survival, and quality of life. Identifying these costs and their impact on health care budgets can help policymakers plan health system expenditure.

Physical function and physical activity in adults with X-linked hypophosphatemia.

We described physical function and activity in UK adults with X-linked hypophosphatemia (XLH). Our data indicate that low physical activity and impaired mobility are common in adults with XLH. Deficits in lower limbs muscle power and functional capacity contribute to the loss of physical function in adults with XLH. INTRODUCTION: There is a dearth of literature on physical function and physical activity in adults with X-linked hypophosphatemia (XLH). We described muscle strength and power, functional capacity, mobility and physical activity level and explored the relationships among these variables in adults with XLH. METHODS: Participants were recruited as part of a UK-based prospective cohort study, the RUDY Study. They underwent a clinical visit and physical examination, including assessment of handgrip strength, jump power (mechanography), six-minute walk test (6MWT) and short physical performance battery (SPPB), and completed the International Physical Activity Questionnaire (IPAQ). Performance data were analysed using parametric and non-parametric tests, whereas correlations were assessed by univariate analysis. RESULTS: Twenty-six adults with XLH (50% males) with a mean age of 44 ± 16.1 years were recruited. Jump power and 6MWT distances (p < 0.0001) were 54.4% and 38.6% lower respectively in individuals with XLH compared with normative values. These deficits were not associated with age or sex. Handgrip strength values were similar to expected values. Deficits in muscle power were more pronounced than those reported at 6MWT (p < 0.0001). Univariate analysis revealed only a correlation between total physical activity and muscle power (r = 0.545, p = 0.019). CONCLUSIONS: Adults with XLH have a marked deficit in lower limb muscle power and a reduced functional capacity, with a high incidence of impaired mobility and inactivity. In addition to metabolic effects of XLH, low physical activity may contribute to deficits in lower limb power. Further studies are required to develop novel treatment approaches to improve physical function and mobility.

International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease.

BACKGROUND: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.