Children and young people's self-reported experiences of asthma and self-management nursing strategies: An integrative review.

AIM: To explore children and young people's (CYP) (5-24 years of age) self-reported experiences of asthma self-management strategies (ASMS) with nursing involvement across various settings. BACKGROUND: Childhood asthma is an increasingly significant health issue, highlighting the importance of acquiring self-management skills to optimise future health outcomes. Registered nurses play a pivotal role in delivering appropriate, personalized self-management support. METHODS: This integrative review searched four electronic databases: Cumulated Index to Nursing and Allied Health Literature via Elton B. Stephens Company, Medical Literature Analysis and Retrieval System Online (MEDLINE), Object, View and Interactive Design (OVID), and PubMed, that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis flowchart. Included studies were critically appraised using the Joanna Briggs Institute critical appraisal tools. Braun and Clarks thematic analysis was used to generate themes, and sub-themes. FINDINGS: Fifteen studies were included for review. Thematic analysis generated three themes being healthy literacy; health and wellbeing; and tools and working together. CONCLUSIONS: Asthma continues to have negative physical, psychological, and social implications among CYP. CYP are both willing and capable of engaging in ASMS and learning self-management skills, however, continue to have unmet self-management needs. IMPLICATIONS TO PRACTICE: Strategies must bolster health literacy, improve physical and psychological health, and harness interactive, youth-centric, and informative tools to facilitate communication and decrease the burden of self-management. Applications pose a promising avenue for self-management support. This age group remains under-explored and future research should enable meaningful engagement with CYP to better understand their perspectives and improve strategy success.

Survival of pre-formed zirconia crowns in primary teeth: a prospective practice-based cohort study.

BACKGROUND: This study aimed to investigate the (1) survival probabilities of prefabricated zirconia crowns (PZCs) placed on primary teeth and (2) identify demographic and tooth-related factors that might affect survival probability. METHODS: This study prospectively followed children treated under general anaesthesia by a single practitioner between 2012 and 2020. Demographic variables including the age at treatment, gender and tooth-related variables including FDI tooth number, crown size used and any procedural complications at postoperative reviews were collected. RESULTS: A total of 155 children involving 319 teeth with PZCs were followed up between 12 and 78 months postoperatively with a mean of 38 months. Of the 319 crowns followed, five failures were observed in three patients requiring extraction. Other procedural complications noted included fracture (n = 3), overhangs (n = 3), internal resorption (n = 5) and 24% of crowns showed signs of radiographic changes on postoperative radiographs when these were taken. Age at treatment, tooth type and need for pulp therapy were not statistically associated with clinical success (P > 0.1). CONCLUSIONS: PZCs provide an aesthetic and durable solution in the management of children with early childhood caries. This study shows very good clinical success and survival extending up to 78 months for PZCs placed on primary teeth under general anaesthesia.

Good manufacturing practice production of CD34+ progenitor-derived NK cells for adoptive immunotherapy in acute myeloid leukemia.

Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34+ hematopoietic stem and progenitor cells (HSPC). This manufacturing process combines amongst others IL15 and IL12 and the aryl hydrocarbon receptor antagonist StemRegenin-1 (SR1) to generate a consistent and active NK cell product that fits the requirements for NK cell immunotherapy well. The cell culture protocol was first optimized to generate NK cells with required expansion and differentiation capacity in GMP-compliant closed system cell culture bags. In addition, phenotype, antitumor potency, proliferative and metabolic capacity were evaluated to characterize the HSPC-NK product. Subsequently, seven batches were manufactured for qualification of the process. All seven runs demonstrated consistent results for proliferation, differentiation and antitumor potency, and preliminary specifications for the investigational medicinal product for early clinical phase trials were set. This GMP-compliant manufacturing process for HSPC-NK cells (named RNK001 cells) is used to produce NK cell batches applied in the clinical trial 'Infusion of ex vivo-generated allogeneic natural killer cells in combination with subcutaneous IL2 in patients with acute myeloid leukemia' approved by the Dutch Ethics Committee (EudraCT 2019-001929-27).

Application of Cell Painting for chemical hazard evaluation in support of screening-level chemical assessments.

'Cell Painting' is an imaging-based high-throughput phenotypic profiling (HTPP) method in which cultured cells are fluorescently labeled to visualize subcellular structures (i.e., nucleus, nucleoli, endoplasmic reticulum, cytoskeleton, Golgi apparatus / plasma membrane and mitochondria) and to quantify morphological changes in response to chemicals or other perturbagens. HTPP is a high-throughput and cost-effective bioactivity screening method that detects effects associated with many different molecular mechanisms in an untargeted manner, enabling rapid in vitro hazard assessment for thousands of chemicals. Here, 1201 chemicals from the ToxCast library were screened in concentration-response up to ∼100 µM in human U-2 OS cells using HTPP. A phenotype altering concentration (PAC) was estimated for chemicals active in the tested range. PACs tended to be higher than lower bound potency values estimated from a broad collection of targeted high-throughput assays, but lower than the threshold for cytotoxicity. In vitro to in vivo extrapolation (IVIVE) was used to estimate administered equivalent doses (AEDs) based on PACs for comparison to human exposure predictions. AEDs for 18/412 chemicals overlapped with predicted human exposures. Phenotypic profile information was also leveraged to identify putative mechanisms of action and group chemicals. Of 58 known nuclear receptor modulators, only glucocorticoids and retinoids produced characteristic profiles; and both receptor types are expressed in U-2 OS cells. Thirteen chemicals with profile similarity to glucocorticoids were tested in a secondary screen and one chemical, pyrene, was confirmed by an orthogonal gene expression assay as a novel putative GR modulating chemical. Most active chemicals demonstrated profiles not associated with a known mechanism-of-action. However, many structurally related chemicals produced similar profiles, with exceptions such as diniconazole, whose profile differed from other active conazoles. Overall, the present study demonstrates how HTPP can be applied in screening-level chemical assessments through a series of examples and brief case studies.

A fresh view of China's OFDI, its motivations and risks thereto.

The aims of this paper are: to examine the key reasons for the locations of and the reasons for China's OFDI as it boomed and became a major OFDI player in the global economy; and, to assess the existence and nature of possible risks to such a boom continuing. The core of the paper, in its second section, is a time-indexed review of findings relating to the first theme noted above. The broad conclusions are that: China's OFDI has been a great success in the period 2005-2019; its motivations have included all the usual possibilities, such as access to resources, market access, access to and reverse engineering of technology (very broadly construed), and access to cheap labour for manufacturing; but, it has also sought to wield political influence via infrastructural investment, and its increasingly hostile attitudes in geopolitical terms in the past decade may pose consequential threats to a continuation of the success to date.

Correction: Character angle effects on dissociated dislocation core energy in aluminum.

Correction for 'Character angle effects on dissociated dislocation core energy in aluminum' by X. W. Zhou et al., Phys. Chem. Chem. Phys., 2021, 23, 3290-3299, DOI: https://doi.org/10.1039/D0CP05333C.

Evaluating structure-based activity in a high-throughput assay for steroid biosynthesis.

Data from a high-throughput human adrenocortical carcinoma assay (HT-H295R) for steroid hormone biosynthesis are available for >2000 chemicals in single concentration and 654 chemicals in multi-concentration (mc). Previously, a metric describing the effect size of a chemical on the biosynthesis of 11 hormones was derived using mc data referred to as the maximum mean Mahalanobis distance (maxmMd). However, mc HT-H295R assay data remain unavailable for many chemicals. This work leverages existing HT-H295R assay data by constructing structure-activity relationships to make predictions for data-poor chemicals, including: (1) identification of individual structural descriptors, known as ToxPrint chemotypes, associated with increased odds of affecting estrogen or androgen synthesis; (2) a random forest (RF) classifier using physicochemical property descriptors to predict HT-H295R maxmMd binary (positive or negative) outcomes; and, (3) a local approach to predict maxmMd binary outcomes using nearest neighbors (NNs) based on two types of chemical fingerprints (chemotype or Morgan). Individual chemotypes demonstrated high specificity (85-98%) for modulators of estrogen and androgen synthesis but with low sensitivity. The best RF model for maxmMd classification included 13 predicted physicochemical descriptors, yielding a balanced accuracy (BA) of 71% with only modest improvement when hundreds of structural features were added. The best two NN models for binary maxmMd prediction demonstrated BAs of 85 and 81% using chemotype and Morgan fingerprints, respectively. Using an external test set of 6302 chemicals (lacking HT-H295R data), 1241 were identified as putative estrogen and androgen modulators. Combined results across the three classification models (global RF model and two local NN models) predict that 1033 of the 6302 chemicals would be more likely to affect HT-H295R bioactivity. Together, these in silico approaches can efficiently prioritize thousands of untested chemicals for screening to further evaluate their effects on steroid biosynthesis.

Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study.

BACKGROUND: There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker. PATIENTS AND METHODS: CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan-Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS. RESULTS: The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608). CONCLUSIONS: High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.

Injury patterns of patients with upper limb and hand trauma sustained during the COVID-19 pandemic lockdown in the UK: a retrospective cohort study.

This work aimed to identify the lead causes of upper limb injury presenting to a busy hand and major trauma unit during the UK COVID-19 domestic lockdown period, in comparison to a cohort from the same period one year previously. Hand and upper limb injuries presenting to the host organization during a pre-lockdown period (23rd March 2019-11th May 2019) and the formal UK lockdown period (23rd March 2020-11th May 2020) were compared, using data collated from the host institution's hand surgery database. The UK lockdown period was associated with a 52% fall in the number of patients presenting to the service with hand and upper limb injuries (589 pre-lockdown vs. 284 during lockdown). There was a significant increase in the proportion of injuries due to machinery use during lockdown (38, 6.5% pre-lockdown vs. 33, 11.6% during lockdown, P = 0.009), other etiologies were consistent. The proportion requiring surgical management were similar (n = 272, 46.2% pre-lockdown vs. n = 138, 48.6% during lockdown, P = 0.50). The proportion requiring overnight admission fell (n = 94, 16.0% pre-lockdown vs. 29, 10.2% during lockdown, P = 0.022). COVID-19 related lockdown in the UK resulted in a reduction in the presenting numbers of hand related injuries; however almost half of these patients still required surgery. These data may be of use to other hand surgery centers for resource planning during future lockdown periods, and for injury prevention strategies in the post-COVID-19 world.

Loneliness and Facebook use: the role of social comparison and rumination.

There is conflicting evidence as to whether Facebook, one of the most popular social networking sites, either promotes social connectedness or contributes to the rising prevalence of loneliness. This study aimed to understand the association between Facebook use and loneliness. Two hundred and fourteen active Facebook users (M age = 35.65; 80.8% female) completed a cross-sectional questionnaire measuring the nature of their Facebook use, how frequently they ruminate, the tendency to compare themselves to their Facebook friends, and upward and downward social comparison. The results showed that rumination and upward social comparison on Facebook were significantly associated with loneliness. The type of activity users engaged in when using Facebook was not significant. The study therefore demonstrates that Facebook users who ruminate and compare themselves to their perceived superiors on Facebook are more likely to experience loneliness. Suggested solutions include raising awareness and using algorithms on Facebook to deliver targeted interventions.

Does CSR Activity Amount to Socially Responsible Management?

In essence firms or companies are usually thought to exist to make products for or provide services of some sort to third parties, other companies or individuals. The philosophical question which naturally arises then is 'to the benefit of whom should a firm's activities be aimed?' Possible answers include the owners of the firm, the firm's employees or wider society, the firm's local community or their host nation. It is because of firms' location within a wider society that the issue of corporate social responsibility arises. The issue is do they contribute in a positive way to the fabric of society. In this paper we conduct an exploratory investigation whose research questions, broadly, are whether there is public evidence of corporate social responsibility activity by firms listed in the UK and to what extent, if any, such activities may amount to genuinely socially responsible management by the firms. We examined the most up to date annual reports of a split sample of 36 firms listed in the FTSE 350. The short answers to the two research questions above are: to some degree and no by some margin, based on data from the sample firms.

Character angle effects on dissociated dislocation core energy in aluminum.

Dislocation core energy is an important property in materials mechanics but can only be obtained from atomistic simulations. Periodic boundary conditions are ideally suited for atomistic calculations of dislocation energies but have faced two major challenges. First, viable methods to extract core energies from atomistic data of total energies have been developed only for non-dissociated dislocations whereas realistic dislocations are often dissociated into partials. Second, core energy is a function of dislocation character angle. This functional dependence can only be revealed through calculations at a variety of character angles. This requires both additional computational resources and a robust method to implement arbitrary character angles. Here a new procedure has been developed to overcome both challenges. By applying this approach, we have calculated 22 core energies of dissociated dislocations in aluminium over the entire character angle range between 0° and 90°. In addition to the discrete core energy data for dissociated dislocations, we found that core energy can be approximated by a continuous function of character angle. Specifically, our dissociated dislocation core energies have been well fitted to a polynomial Sinoidal function of character angle. We have also discovered that there exists a critical system dimension below which dislocation core energies cannot be calculated due to dislocation transformation.

Bariatric Surgery for Congestive Heart Failure Patients Improves Access to Transplantation and Long-term Survival.

INTRODUCTION: Obese patients with congestive heart failure (CHF) are often denied access to heart transplantation until they obtain significant weight loss to achieve a certain BMI threshold, often less than 35 kg/m2. It is unknown whether the rapid weight loss associated with bariatric surgery leads to improved waitlist placement, and as such improved survival for morbidly obese patients with CHF. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with CHF who were deemed ineligible to be waitlisted for heart transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following medical weight management (MWM), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with both SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 2.1 additional years of life compared with patient's who underwent SG and 7.4 additional years of life compared with MWM. SG patients gained 5.3 years of life compared with MWM. CONCLUSIONS: When strict waitlist criteria were applied, bariatric surgery improved access to heart transplantation and thereby increased long-term survival compared with MWM. Morbidly obese CHF patients who anticipate need for heart transplantation should be encouraged to pursue surgical weight management strategies, necessitating discussion between bariatric surgeons, cardiologists, and cardiac surgeons for appropriate perioperative risk management.

Reflecting on success in trauma research: experiences from the SGCNS and SIR studies.

The inclusion of British Service Personnel (SP) lacking capacity into research studies from the point of injury through to medium-term rehabilitation had not previously been undertaken until work to support operations in Afghanistan (2001-2014). The Surgeon General's Casualty Nutrition Study and the Steroids and Immunity from Injury through to Rehabilitation Study sought to address the nutrition, endocrine and immune responses in a military patient cohort. A fundamental part of research is to feedback to patients, their relatives and ward staff on data collection and outcomes, and how future research may be improved to better support both injured SP and trauma patients in the UK. This paper will provide an experiential view on the delivery, operations and infrastructure requirements that should be considered when developing military research at a role-3 facility, before, during and after a study.

A modified silent substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs.

OBJECTIVE: A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using silent substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED: Three normal adult purpose-bred beagles (2 females and 1 male). METHODS: Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS: In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P < .001). CONCLUSION: We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury.

BACKGROUND: Circulating cell-free DNA (cfDNA) is not found in healthy subjects, but is readily detected after thermal injury and may contribute to the risk of multiple organ failure. The hypothesis was that a postburn reduction in DNase protein/enzyme activity could contribute to the increase in cfDNA following thermal injury. METHODS: Patients with severe burns covering at least 15 per cent of total body surface area were recruited to a prospective cohort study within 24 h of injury. Blood samples were collected from the day of injury for 12 months. RESULTS: Analysis of blood samples from 64 patients revealed a significant reduction in DNase activity on days 1-28 after injury, compared with healthy controls. DNase protein levels were not affected, suggesting the presence of an enzyme inhibitor. Further analysis revealed that actin (an inhibitor of DNase) was present in serum samples from patients but not those from controls, and concentrations of the actin scavenging proteins gelsolin and vitamin D-binding protein were significantly reduced after burn injury. In a pilot study of ten military patients with polytrauma, administration of blood products resulted in an increase in DNase activity and gelsolin levels. CONCLUSION: The results of this study suggest a novel biological mechanism for the accumulation of cfDNA following thermal injury by which high levels of actin released by damaged tissue cause a reduction in DNase activity. Restoration of the actin scavenging system could therefore restore DNase activity, and reduce the risk of cfDNA-induced host tissue damage and thrombosis.

ANTECEDENTES: El ADN libre de las células circulantes (circulating cell-free DNA, cfDNA) no se encuentra en sujetos sanos, pero se detecta fácilmente después de una lesión térmica y puede contribuir al riesgo de fallo multiorgánico. La hipótesis fue que una disminución en la actividad de la proteína/enzima ADNasa tras la lesión térmica podría contribuir a la elevación del cfDNA que ocurre tras la misma. MÉTODOS: Los pacientes con quemaduras graves con una extensión ≥ 15% del área de superficie corporal total (total body surface area, TBSA) se incluyeron en un estudio prospectivo de cohortes durante las primeras 24 horas posteriores a la lesión. Se recogieron muestras de sangre desde el día de la lesión hasta los 12 meses posteriores a la misma. RESULTADOS: El análisis de muestras de sangre de 64 pacientes reveló una reducción significativa de la actividad de la ADNasa en los días 1 a 28 después de la lesión, en comparación con los controles sanos. Los niveles de proteína ADNasa no se vieron afectados, lo que sugiere la presencia de un inhibidor enzimático. Un análisis adicional reveló que la actina (un inhibidor de la ADNasa) estaba presente en las muestras de suero de los pacientes, pero no en los controles, y las concentraciones de la gelsolina, proteína que causa la disociación de la actina, y la proteína de unión a la vitamina D se redujeron significativamente después de la lesión térmica. En un estudio piloto de 10 pacientes con politrauma por lesiones militares, la administración de hemoderivados produjo un aumento en la actividad de la ADNasa y de los niveles de gelsolina. CONCLUSIÓN: Este estudio sugiere un nuevo mecanismo biológico para la acumulación de cfDNA después de una lesión térmica, por el cual los altos niveles de actina liberada por el tejido dañado causarían una reducción en la actividad de la ADNasa. La restauración del sistema eliminador de actina podría, por lo tanto, restaurar la actividad de la ADNasa y reducir el riesgo de daño tisular y trombosis en el huésped inducido por el cfDNA.

Molecular dynamics discovery of an extraordinary ionic migration mechanism in dislocation-containing TlBr crystals.

TlBr can surpass CZT as the leading semiconductor for γ- and X-radiation detection. Unfortunately, the optimum properties of TlBr quickly decay when an operating electrical field is applied. Quantum mechanical studies indicated that if this property degradation comes from the conventional mechanism of ionic migration of vacancies, then an unrealistically high vacancy concentration is required to account for the rapid aging of TlBr seen in experiments. In this work, we have applied large scale molecular dynamics simulations to study the effects of dislocations on ionic migration of TlBr crystals under electrical fields. We found that electrical fields can drive the motion of edge dislocations in both slip and climb directions. These combined motions eject enormous vacancies in the dislocation trail. Both dislocation motion and a high vacancy concentration can account for the rapid aging of the TlBr detectors. These findings suggest that strengthening methods to pin dislocations should be explored to increase the lifetimes of TlBr crystals.

Multichannel processing of vibrational measurements: A constrained subspace application.

Monitoring mechanical systems operating in uncertain environments contaminated with both environmental disturbances and noise lead directly to low signal-to-noise-ratios, creating an extremely challenging processing problem, especially in real-time. In order to estimate the performance of a particular system from uncertain vibrational data, it is necessary to identify its unique resonant (modal) frequency signature. The monitoring of structural modes to determine the condition of a device under investigation is essential, especially if it is a critical entity of an operational system. The development of a model-based scheme capable of the on-line tracking of the inherent structural modal frequencies by applying both constrained subspace identification techniques to extract the modal frequencies and state estimation methods to track the evolution is discussed. An application of this approach to a cylindrical structural device (pipe-in-air) is analyzed based on theoretical simulations along with controlled validation experiments, including injected anomalies illustrate the approach and performance. Statistics are gathered to bound potential processors for real-time performance employing these constrained techniques.