bluuebunny/crossref_metadata_2025 huggingface dataset:
Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders
Authors: DeSouza Noah M. , Brewster L. Madden , Bain Anthony R. , Garcia Vinicius P. , Stone Rachel , Stockelman Kelly A. , Greiner Jared J. , Tymko Michael M. , Vizcardo‐Galindo Gustavo , Figueroa‐Mujica Romulo J. , Villafuerte Francisco C. , Ainslie Philip N. , DeSouza Christopher A.
Published: March 2021

New Findings

What is the central question of this study?

Are coagulation and fibrinolytic factors disrupted in Andean highlanders with excessive erythrocytosis?

What is the main finding and its importance?

Excessive erythrocytosis is not associated with prothombotic disruptions in coagulation or the fibrinolytic system in Andean highlanders. Impairments in coagulation and fibrinolysis may not contribute to the increased vascular risk associated with excessive erythrocytosis.

Increased coagulation and reduced fibrinolysis are central factors underlying thrombotic risk and events. High altitude‐induced excessive erythrocytosis (EE) is prevalent in Andean highlanders, contributing to increased cardiovascular risk. Disruption in the coagulation–fibrinolytic axis resulting in uncontrolled fibrin deposition might underlie the increased thrombotic risk associated with high‐altitude EE. The experimental aim of this study was to determine whether EE is associated with a prothrombotic blood coagulation and fibrinolytic profile in Andean highlanders. Plasma coagulation factors (von Willebrand factor and factors VII, VIII and X), fibrinolytic factors [tissue‐type plasminogen activator (t‐PA) and plasminogen activator inhibitor‐1 (PAI‐1)] and D‐dimer levels were determined in 26 male residents of Cerro de Pasco, Peru (4340 m a.s.l.): 12 without EE (age, 40 ± 13 years; haemoglobin, 17.4 ± 1.9 g/dl) and 14 with EE (age, 43 ± 15 years; haemoglobin, 24.4 ± 1.6 g/dl). There were no significant differences in von Willebrand factor (40.5 ± 24.8 vs. 45.5 ± 22.4%), factor VII (77.0 ± 14.5 vs. 72.5 ± 8.9%), factor VIII (55.6 ± 19.8 vs. 60.7 ± 26.8%) and factor X (73.9 ± 8.3 vs. 67.3 ± 10.9%) between the Andean highlanders without or with EE. The t‐PA antigen (8.5 ± 3.6 vs. 9.6 ± 5.4 ng/ml), t‐PA activity (5.5 ± 2.4 vs. 5.8 ± 1.6 IU/ml), PAI antigen (45.0 ± 33.8 vs. 40.5 ± 15.8 ng/ml), PAI‐1 activity (0.24 ± 0.09 vs. 0.25 ± 0.11 IU/ml) and the molar concentration ratio of active t‐PA to active PAI‐1 (1:0.051 ± 0.034 vs. 1:0.046 ± 0.021 mmol/l) were also similar between the groups, as were D‐dimer levels (235.0 ± 126.4 vs. 268.4 ± 173.7 ng/ml). Collectively, the results of the present study indicate that EE is not associated with a hypercoagulable, hypofibrinolytic state in Andean highlanders.
Short‐term sleep deprivation and human thermoregulatory function during thermal challenges
Authors: Keramidas Michail E. , Botonis Petros G.
Published: March 2021

New Findings

What is the topic of this review?

It is generally accepted that sleep deprivation constitutes a predisposing factor to the development of thermal injury. This review summarizes the available human‐based evidence on the impact of sleep loss on autonomic and behavioural thermoeffectors during acute exposure to low and high ambient temperatures.

What advances does it highlight?

Limited to moderate evidence suggests that sleep deprivation per se impairs thermoregulatory defence mechanisms during exposure to thermal extremes. Future research is required to establish whether inadequate sleep enhances the risk for cold‐ and heat‐related illnesses.

Relatively short periods of inadequate sleep provoke physiological and psychological perturbations, typically leading to functional impairments and degradation in performance. It is commonly accepted that sleep deprivation also disturbs thermal homeostasis, plausibly enhancing susceptibility to cold‐ and heat‐related illnesses. Herein, we summarize the current state of human‐based evidence on the impact of short‐term (i.e., ≤4 nights) sleep deprivation on autonomic and behavioural thermoeffectors during acute exposure to low and high ambient temperatures. The purpose of this brief narrative review is to highlight knowledge gaps in the area and stimulate future research to investigate whether sleep deprivation constitutes a predisposing factor for the development of thermal injuries.
Haemodynamics and cerebral oxygenation of neonatal piglets in the immediate ex utero period supported by mechanical ventilation or ex utero oxygenator
Authors: Darby Jack R.T. , Berry Mary J. , Quinn Megan , Holman Stacey L. , Bradshaw Emma L. , Jesse Sarah M. , Haller Christoph , Seed Mike , Morrison Janna L.
Published: March 2021

Key points

The margin of human viability has extended to the extremes of gestational age (<24 weeks) when the lungs are immature and ventilator‐induced lung injury is common.

Artificial placenta technology aims to extend gestation ex utero in order to allow the lungs additional time to develop prior to entering an air‐breathing environment.

We compared the haemodynamics and cerebral oxygenation of piglets in the immediate period post‐oxygenator (OXY) transition against both paired in utero measures and uniquely against piglets transitioned onto mechanical ventilation (VENT).

Post‐transition, OXY piglets became hypotensive with reduced carotid blood flow in comparison with both paired in utero measures and VENT piglets.

The addition of a pump to the oxygenator circuit may be required to ensure haemodynamic stability in the immediate post‐transition period.

Gestational age at birth is a major predictor of wellbeing; the lower the gestational age, the greater the risk of mortality and morbidity. At the margins of human viability (<24 weeks gestation) immature lungs combined with the need for early ventilatory support means lung injury and respiratory morbidity is common. The abrupt haemodynamic changes consequent on birth may also contribute to preterm‐associated brain injury, including intraventricular haemorrhage. Artificial placenta technology aims to support oxygenation, haemodynamic stability and ongoing fetal development ex utero until mature enough to safely transition to a true ex utero environment. We aimed to characterize the impact of birth transition onto either an oxygenator circuit or positive pressure ventilation on haemodynamic and cerebral oxygenation of the neonatal piglet. At 112 days gestation (term = 115 days), fetal pigs underwent instrumentation surgery and transitioned onto either an oxygenator (OXY, n = 5) or ventilatory support (VENT, n = 8). Blood pressure (BP), carotid blood flow and cerebral oxygenation in VENT piglets rose from in utero levels to be significantly higher than OXY piglets post‐transition. OXY piglet BP, carotid blood flow and carotid oxygen delivery (DO2) decreased from in utero levels post‐transition; however, cerebral regional oxygen saturation (rSO2) was maintained at fetal‐like levels. OXY piglets became hypoxaemic and retained CO2. Whether OXY piglets are able to maintain cerebral rSO2 under these conditions for a prolonged period is yet to be determined. Improvements to OXY piglet oxygenation may lie in maintaining piglet BP at in utero levels and enhancing oxygenator circuit flow.
JAK/STAT inhibition augments soleus muscle function in a rat model of critical illness myopathy via regulation of complement C3/3R
Authors: Addinsall Alex B. , Cacciani Nicola , Akkad Hazem , Salah Heba , Tchkonia Tamara , Kirkland James L. , Larsson Lars
Published: March 2021

Key points

Critical illness myopathy (CIM) is a frequently observed negative consequence of modern critical care.

Chronic Janus kinase (JAK)/signal transducer and activator of transcription activation impairs muscle size and function and is prominent following mechanical ventilation.

We identify pSTAT‐3 activation in tibialis anterior of CIM patients, before examining the potential benefits of JAK1/2 inhibition in an experimental model of CIM, where muscle mass and function are impaired.

CIM activates complement cascade and increased monocyte infiltration in the soleus muscle, which was ameliorated by JAK1/2 inhibition, leading to reduced muscle degeneration and improved muscle force.

Here, we demonstrate that JAK1/2 inhibition augments CIM muscle function through regulation of the complement cascade.

Critical illness myopathy (CIM) is frequently observed in response to modern critical care with negative consequences for patient quality of life, morbidity, mortality and healthcare costs. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) activation is observed in limb muscles following controlled mechanical ventilation. Chronic JAK/STAT activation promotes loss of muscle mass and function. Thus, we hypothesized that JAK1/2 inhibition would improve muscle outcomes for CIM. Following 12 days of intensive care unit conditions, pSTAT‐3 levels increased in tibialis anterior muscle of CIM patients (P = 0.0489). The potential of JAK1/2 inhibition was assessed in an experimental model of CIM, where soleus muscle size and force are impaired. JAK1/2 inhibition restores soleus force (P < 0.0001). CIM activated muscle complement cascade, which was ameliorated by JAK1/2 inhibition (P < 0.05, respectively). Soleus macrophage number corresponded with complement activity, leading to reduced muscle degeneration and augmented muscle function (P < 0.05). Thus, JAK/STAT inhibition improves soleus function by modulating the complement cascade and muscle monocyte infiltration. Collectively, we demonstrate that JAK/STAT inhibition augments muscle function in CIM.
Does a Multicomponent Exercise Program Improve Physical Fitness in Older Adults? Findings From a 5-Year Longitudinal Study
Authors: Gonçalves Andréa Kruger , Griebler Eliane Mattana , da Silva Wagner Albo , Sant´Helena Débora Pastoriza , da Silva Priscilla Cardoso , Possamai Vanessa Dias , Martins Valéria Feijó
Published: March 2021

The objective was to assess the physical fitness of older adults participating in a 5-year multicomponent exercise program. The sample consisted of 138 older adults aged 60–93 years (70.4 ± 7.8 years) evaluated with the Senior Fitness Test (muscle strength, flexibility, balance, and cardiorespiratory fitness). The multicomponent program was carried out between the months of March and November of each year. Data were analyzed using generalized estimating equations (factor year: Year 1, Year 2, Year 3, Year 4, and Year 5; factor time: pretest and posttest) with Bonferroni’s post hoc test. Participation in the multicomponent exercise program for 5 years (baseline pretest Year 1 and follow-up Year 5) improved lower and upper limb strength, lower limb flexibility, and balance and cardiorespiratory fitness, while upper limb flexibility was maintained. Year-by-year analysis revealed variable patterns for each fitness parameter. The results of this study show the potential benefits of implementing a long-term community-based exercise program.
Reinforcement learning with artificial microswimmers
Authors: Muiños-Landin S. , Fischer A. , Holubec V. , Cichos F.
Published: March 2021

Microscopic active particles exhibit adaptive behavior under real-world conditions with reinforcement learning.
Draft Genome Sequences of
Blastococcus
sp. Clones TML/M2B and TML/C7B, with Different Motilities, Isolated in a Laboratory
Authors: Liao Hsiao-Mei , Li Bingjie , Tsai Shien , Liu Hebing , Hung Guo-Chiuan , Lo Shyh-Ching
Published: March 2021

Two novel
Blastococcus
sp. clones, TML/M2B and TML/C7B, with 2 stable different growth phenotypes, were isolated from a laboratory tissue culture. The draft genome sequences generated through genomic sequencing of clones TML/M2B and TML/C7B contain 4 and 2 contigs, respectively. The respective genome sizes are 4.10 Mb and 4.11 Mb, with GC contents of 74.17% and 74.14%.
Eye care delivery models to improve access to eye care for Indigenous peoples in high-income countries: a scoping review
Authors: Burn Helen , Hamm Lisa , Black Joanna , Burnett Anthea , Harwood Matire , Burton Matthew J , Evans Jennifer R , Ramke Jacqueline
Published: March 2021

Purpose

Globally, there are ~370 million Indigenous peoples. Indigenous peoples typically experience worse health compared with non-Indigenous people, including higher rates of avoidable vision impairment. Much of this gap in eye health can be attributed to barriers that impede access to eye care services. We conducted a scoping review to identify and summarise service delivery models designed to improve access to eye care for Indigenous peoples in high-income countries.

Methods

Searches were conducted on MEDLINE, Embase and Global Health in January 2019 and updated in July 2020. All study designs were eligible if they described a model of eye care service delivery aimed at populations with over 50% Indigenous peoples. Two reviewers independently screened titles, abstracts and full-text articles and completed data charting. We extracted data on publication details, study context, service delivery interventions, outcomes and evaluations, engagement with Indigenous peoples and access dimensions targeted. We summarised findings descriptively following thematic analysis.

Results

We screened 2604 abstracts and 67 studies fulfilled our eligibility criteria. Studies were focused on Indigenous peoples in Australia (n=45), USA (n=11), Canada (n=7), New Zealand (n=2), Taiwan (n=1) and Greenland (n=1). The main disease focus was diabetic retinopathy (n=30, 45%), followed by ‘all eye care’ (n=16, 24%). Most studies focused on targeted interventions to increase availability of services. Fewer than one-third of studies reported involving Indigenous communities when designing the service. 41 studies reflected on whether the model improved access, but none undertook rigorous evaluation or quantitative assessment.

Conclusions

The geographical and clinical scope of service delivery models to improve access to eye care for Indigenous peoples in high-income countries is narrow, with most studies focused on Australia and services for diabetic retinopathy. More and better engagement with Indigenous communities is required to design and implement accessible eye care services.
Implementation of a full-scale prehospital telemedicine system: evaluation of the process and systemic effects in a pre–post intervention study
Authors: Bergrath Sebastian , Brokmann Jörg Christian , Beckers Stefan , Felzen Marc , Czaplik Michael , Rossaint Rolf
Published: March 2021

Objectives

To review the implementation strategy from a research project towards routine care of a comprehensive mobile physician-staffed prehospital telemedicine system. The objective is to evaluate the implementation process and systemic influences on emergency medical service (EMS) resource utilisation.

Design

Retrospective pre–post implementation study.

Setting

Two interdisciplinary projects and the EMS of a German urban region.

Interventions

Implementation of a full-scale prehospital telemedicine system.

Endpoints

Descriptive evaluation of the implementation strategy. Primary endpoint: ground-based and helicopter-based physician staffed emergency missions before and after implementation.

Results

The first research project revealed positive effects on guideline adherence and patient safety in two simulation studies, with feasibility demonstrated in a clinical study. After technical optimisation, safety and positive effects were demonstrated in a multicentre trial. Routine care in the city of Aachen, Germany was conducted stepwise from April 2014 to March 2015, including modified dispatch criteria. Systemic parameters of all EMS assignments between pre-implementation (April 2013 to March 2014) and post implementation (April 2015 to March 2016): on-scene EMS physician operations decreased from 7882/25 187 missions (31.3%) to 6360/26 462 (24.0%), p<0.0001. The need for neighbouring physician-staffed units dropped from 234/25 187 (0.93%) to 119/26 462 (0.45%), p<0.0001, and the need for helicopter EMS from 198/25 187 (0.79%) to 100/26 462 (0.38%), p<0.0001. In the post implementation period 2347 telemedical interventions were conducted, with 26 462 emergency missions (8.87%).

Conclusion

A stepwise implementation strategy allowed transfer from the project phase to routine care. We detected a reduced need for conventional on-scene physician care by ground-based and helicopter-based EMS, but cannot exclude unrecognised confounders, including modified dispatch criteria and possible learning effects. This creates the potential for increased availability of EMS physicians for life-threatening emergencies by shifting physician interventions from conventional to telemedical care.

Trial registration number

NCT04127565.
RxIALTA: evaluating the effect of a pharmacist-led intervention on CV risk in patients with chronic inflammatory diseases in a community pharmacy setting: a prospective pre–post intervention study
Authors: Al Hamarneh Yazid N , Marra Carlo , Gniadecki Robert , Keeling Stephanie , Morgan Andrea , Tsuyuki Ross
Published: March 2021

Patients with inflammatory conditions are at high risk for cardiovascular (CV) disease. Despite such elevated risk, their CV risk factors are suboptimally managed.

Objective

To evaluate the effect of a pharmacist-led intervention on CV risk in patients with inflammatory conditions.

Methods

Design

Prospective pre–postintervention.

Setting

17 community pharmacies across Alberta.

Population

Adults with inflammatory conditions (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, systemic lupus erythematosus, psoriasis vulgaris) who had at least one uncontrolled risk factor (A1C, blood pressure, LDL-cholesterol or current tobacco users).

Intervention

All patients enrolled in the study received: physical and laboratory assessment, individualised CV risk assessment and education regarding this risk, treatment recommendations, prescription adaptation and prescribing where necessary to meet treatment targets, regular communication with the patient’s treating physician(s) and regular follow-up with all patients every month for 6 months.

Outcomes

Primary: change in estimated CV risk (risk of a major CV event in the next 10 years) after 6 months. Secondary: change in individual risk factors (blood pressure, LDL-cholesterol, A1C and tobacco cessation) over a 6-month period.

Results

We enrolled 99 patients. The median age was 66.41 years (IQR 57.64–72.79), More than half of them (61%) were female and more than three-quarters (86%) were Caucasians. After adjusting for age, sex and ethnicity and centre effect, there was a reduction of 24.5% in CV risk (p<0.001); including a reduction of 0.3 mmol/L in LDL-c (p<0.001), 10.7 mm Hg in systolic blood pressure (p<0.001), 1.25% in A1C (p<0.001). There was a non-significant trend towards tobacco cessation.

Conclusion

This is the first study on CV risk reduction in patients with inflammatory conditions in a community pharmacy setting. RxIALTA provides evidence for the benefit of pharmacist care on global cardiovascular risk reduction as well as the individual cardiovascular risk factors in patients with inflammatory conditions.

Trial registration number

NCT03152396.
Health insurance utilisation after ischaemic stroke in Sweden: a retrospective cohort study in a system of universal healthcare and social insurance
Authors: Willers Carl , Westerlind Emma , Borgström Fredrik , von Euler Mia , Sunnerhagen Katharina S
Published: March 2021

Background

Stroke is one of the largest single-condition sources of the global burden of non-communicable disease in terms of disability-adjusted life-years and monetary costs, directly as well as indirectly in terms of informal care and productivity loss. The objective was to assess the population afflicted with ischaemic stroke in working age in the context of universal healthcare and social insurance; to estimate the levels of absence from work, the indirect costs related to that and to assess the associated patient characteristics.

Methods

This was a retrospective register-based study; all individuals registered with an ischaemic stroke during 2008–2011 in seven Swedish regions, covering the largest cities as well as more rural areas, were included. Individual-level data were used to compute net days of sick leave and disability pension, indirect costs due to productivity loss and to perform regression analysis on net absence from work to assess the associated factors. Costs related to productivity loss were estimated using the human capital approach.

Results

Women had significantly fewer net days of sick leave and disability pension than men after multivariable adjustment, and high-income groups had higher levels of sick leave than low-income groups. There were no significant differences for participants regarding educational level, region of birth or civil status. Indirect monetary costs amounted to €17 400 per stroke case during the first year, totalling approximately €169 million in Sweden.

Conclusion

The individual’s burden of stroke is heavy in terms of morbidity, and the related productivity loss for society is immense. Income-group differences point to a socioeconomic gradient in the utilisation of the Swedish social insurance.
How well can we assess the validity of non-randomised studies of medications? A systematic review of assessment tools
Authors: D'Andrea Elvira , Vinals Lydia , Patorno Elisabetta , Franklin Jessica M. , Bennett Dimitri , Largent Joan A. , Moga Daniela C. , Yuan Hongbo , Wen Xuerong , Zullo Andrew R. , Debray Thomas P. A. , Sarri Grammati
Published: March 2021

Objective

To determine whether assessment tools for non-randomised studies (NRS) address critical elements that influence the validity of NRS findings for comparative safety and effectiveness of medications.

Design

Systematic review and Delphi survey.

Data sources

We searched PubMed, Embase, Google, bibliographies of reviews and websites of influential organisations from inception to November 2019. In parallel, we conducted a Delphi survey among the International Society for Pharmacoepidemiology Comparative Effectiveness Research Special Interest Group to identify key methodological challenges for NRS of medications. We created a framework consisting of the reported methodological challenges to evaluate the selected NRS tools.

Study selection

Checklists or scales assessing NRS.

Data extraction

Two reviewers extracted general information and content data related to the prespecified framework.

Results

Of 44 tools reviewed, 48% (n=21) assess multiple NRS designs, while other tools specifically addressed case–control (n=12, 27%) or cohort studies (n=11, 25%) only. Response rate to the Delphi survey was 73% (35 out of 48 content experts), and a consensus was reached in only two rounds. Most tools evaluated methods for selecting study participants (n=43, 98%), although only one addressed selection bias due to depletion of susceptibles (2%). Many tools addressed the measurement of exposure and outcome (n=40, 91%), and measurement and control for confounders (n=40, 91%). Most tools have at least one item/question on design-specific sources of bias (n=40, 91%), but only a few investigate reverse causation (n=8, 18%), detection bias (n=4, 9%), time-related bias (n=3, 7%), lack of new-user design (n=2, 5%) or active comparator design (n=0). Few tools address the appropriateness of statistical analyses (n=15, 34%), methods for assessing internal (n=15, 34%) or external validity (n=11, 25%) and statistical uncertainty in the findings (n=21, 48%). None of the reviewed tools investigated all the methodological domains and subdomains.

Conclusions

The acknowledgement of major design-specific sources of bias (eg, lack of new-user design, lack of active comparator design, time-related bias, depletion of susceptibles, reverse causation) and statistical assessment of internal and external validity is currently not sufficiently addressed in most of the existing tools. These critical elements should be integrated to systematically investigate the validity of NRS on comparative safety and effectiveness of medications.

Systematic review protocol and registration

https://osf.io/es65q.
Hospital-based acute care in the last 30 days of life among patients with chronic disease that received early, late or no specialist palliative care: a retrospective cohort study of eight chronic disease groups
Authors: Earp Madalene , Cai Pin , Fong Andrew , Blacklaws Kelly , Pham Truong-Minh , Shack Lorraine , Sinnarajah Aynharan
Published: March 2021

Objective

For eight chronic diseases, evaluate the association of specialist palliative care (PC) exposure and timing with hospital-based acute care in the last 30 days of life.

Design

Retrospective cohort study using administrative data.

Setting

Alberta, Canada between 2007 and 2016.

Participants

47 169 adults deceased from: (1) cancer, (2) heart disease, (3) dementia, (4) stroke, (5) chronic lower respiratory disease (chronic obstructive pulmonary disease (COPD)), (6) liver disease, (7) neurodegenerative disease and (8) renovascular disease.

Main outcome measures

The proportion of decedents who experienced high hospital-based acute care in the last 30 days of life, indicated by ≥two emergency department (ED) visit, ≥two hospital admissions,≥14 days of hospitalisation, any intensive care unit (ICU) admission, or death in hospital. Relative risk (RR) and risk difference (RD) of hospital-based acute care given early specialist PC exposure (≥90 days before death), adjusted for patient characteristics.

Results

In an analysis of all decedents, early specialist PC exposure was associated with a 32% reduction in risk of any hospital-based acute care as compared with those with no PC exposure (RR 0.69, 95% CI 0.66 to 0.71; RD 0.16, 95% CI 0.15 to 0.17). The association was strongest in cancer-specific analyses (RR 0.53, 95% CI 0.50 to 0.55; RD 0.31, 95% CI 0.29 to 0.33) and renal disease-specific analyses (RR 0.60, 95% CI 0.43 to 0.84; RD 0.22, 95% CI 0.11 to 0.34), but a~25% risk reduction was observed for each of heart disease, COPD, neurodegenerative diseases and stroke. Early specialist PC exposure was associated with reducing risk of four out of five individual indicators of high hospital-based acute care in the last 30 days of life, including ≥two ED visit,≥two hospital admission, any ICU admission and death in hospital.

Conclusions

Early specialist PC exposure reduced the risk of hospital-based acute care in the last 30 days of life for all chronic disease groups except dementia.
MUKnineOPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia
Authors: Brown Sarah , Sherratt Debbie , Hinsley Samantha , Flanagan Louise , Roberts Sadie , Walker Katrina , Hall Andrew , Pratt Guy , Messiou Christina , Jenner Matthew , Kaiser Martin
Published: March 2021

Introduction

Multiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients.

Methods and analysis

The Myeloma UKnineOPTIMUM trial (MUKnine) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUKnine a), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUKnine b) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUKnine bprimary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing.

Ethics and dissemination

Ethics approval London South East Research Ethics Committee (Ref: 17/LO/0022, 17/LO/0023). Results of studies will be submitted for publication in a peer-reviewed journal.

Trial registration number

ISRCTN16847817, May 2017; Pre-results.
Acceptance and commitment therapy (ACT)-enhanced communication skills: development and evaluation of a novel training programme
Authors: Hulbert-Williams Nicholas J , Hulbert-Williams Lee , Patterson Pandora , Suleman Sahil , Howells Lesley
Published: March 2021

Background

Psychological suffering is ubiquitous with cancer and frequently presents as an unmet supportive care need. In clinical practice, distress-related needs are often addressed by nurses and non-psychologist allied healthcare professionals who may have limited training in psychological therapeutic frameworks, particularly more recently developed interventions such as Acceptance and Commitment Therapy (ACT).

Aims

We developed a single-day training programme for professionals working in supportive and palliative cancer care settings to change the nature of clinical communication about psychological distress and suffering towards an ACT-consistent approach.

Method

We report on experiences of training delivery, and evaluation data about training satisfaction and intention to apply the training to clinical practice, from three training iterations in British and Australian, government-funded and charitable sectors. One hundred and sixteen cancer care professionals participated in the training. Evaluation data were collected from 53 participants (at either 2-week or 3-month follow-ups, or both) using self-report survey, including both quantitative and free-text questions.

Results

At 2 week follow-up, 73% of trainees rating our course as having relevance to their work, and at 3 month follow-up, 46% agreed that they were better placed to provide improved clinical services. Qualitative feedback supported the inclusion of experiential learning and theoretical explanations underpinning ACT techniques. Undertaking this training did not significantly increase trainees’ stress levels, nor did implementation of this new way of working negatively affect staff well-being. Positive, ACT-consistent, changes in communication behaviours and attitudes were reported, however there was a lack of significant change in psychological flexibility.

Discussion

Acceptability and applicability of this training to supportive and palliative healthcare is positive. The lack of change in psychological flexibility suggests a potential need for more experiential content in the training programme. Logistical challenges in one training group suggests the need for more robust train-the-trainer models moving forward.
Energy condition in unimodular f(R, T) gravity
Authors: Rajabi Fateme , Nozari Kourosh
Published: March 2021

We study an interesting alternative of modified gravity theory, namely, the unimodular f(R, T) gravity in which R is the Ricci scalar and T is the trace of the stress–energy tensor. We study the viability of the model by using the energy conditions. We discuss the strong, weak, null and dominant energy conditions in terms of deceleration, jerk and snap parameters. We investigate energy conditions for reconstructed unimodular f(R, T) models and give some constraints on the parametric space of the model. We observe that by setting appropriately free parameters, energy conditions can be satisfied. Furthermore, we study the stability of the solutions in perturbations framework. In this case, we investigate stability conditions for de Sitter and power law solutions and we examine viability of cosmological evolution of these perturbations. The results show that for some values of the input parameters, for which energy conditions are satisfied, de Sitter and power-law solutions may be stable.
Scalar and vector perturbations in a universe with nonlinear perfect fluid
Authors: Canay Ezgi , Brilenkov Ruslan , Eingorn Maxim , Arapoğlu A. Savaş , Zhuk Alexander
Published: March 2021

We study a three-component universe filled with dust-like matter in the form of discrete inhomogeneities (e.g., galaxies) and perfect fluids characterized by linear and nonlinear equations of state. Within the cosmic screening approach, we develop the theory of scalar and vector perturbations. None of the energy density contrasts associated with the distinct components is treated as small. Consequently, the derived equations are valid at both sub- and super-horizon scales and enable simulations for a variety of cosmological models.
No short hair behaviors of ultra-compact stars
Authors: Peng Yan
Published: March 2021

In the black hole spacetime, a no short hair theorem was proved, which states that the effective radius of black hole hairs must extend beyond the null circular orbit. In the present paper, in the horizonless gravity, we find a similar no short hair behavior that the effective radius of matter fields must also extend beyond the null circular orbit of ultra-compact stars. We should emphasize that the theorem presented in this manuscript is valid only for spatially regular matter configurations whose energy-momentum traces are non-negative.
Optical tweezers in a dusty universe
Authors: Polimeno P. , Magazzù A. , Iatì M. A. , Saija R. , Folco L. , Bronte Ciriza D. , Donato M. G. , Foti A. , Gucciardi P. G. , Saidi A. , Cecchi-Pestellini C. , Jimenez Escobar A. , Ammannito E. , Sindoni G. , Bertini I. , Della Corte V. , Inno L. , Ciaravella A. , Rotundi A. , Maragò O. M.
Published: March 2021

Optical tweezers are powerful tools based on focused laser beams. They are able to trap, manipulate, and investigate a wide range of microscopic and nanoscopic particles in different media, such as liquids, air, and vacuum. Key applications of this contactless technique have been developed in many fields. Despite this progress, optical trapping applications to planetary exploration are still to be developed. Here we describe how optical tweezers can be used to trap and characterize extraterrestrial particulate matter. In particular, we exploit light scattering theory in the T-matrix formalism to calculate radiation pressure and optical trapping properties of a variety of complex particles of astrophysical interest. Our results open perspectives in the investigation of extraterrestrial particles on our planet, in controlled laboratory experiments, aiming forspace tweezersapplications: optical tweezers used to trap and characterize dust particles in space or on planetary bodies surface.
EXACT DIMENSIONS OF EXCEPTIONAL SETS IN LÜROTH EXPANSIONS
Authors: FENG YAN , TAN BO , ZHOU QING-LONG
Published: March 2021

For [Formula: see text], let [Formula: see text] be its Lüroth expansion, and let [Formula: see text] be the sequence of convergents of [Formula: see text] Define the exceptional sets [Formula: see text] and [Formula: see text] Arroyo and González Robert [Hausdorff dimension of sets of numbers with large Lüroth elements, preprint (2020), arXiv:2010.13932] presented upper and lower bound estimations for the Hausdorff dimension of [Formula: see text]. In this paper, we determine the Hausdorff dimensions of the sets [Formula: see text] as well as [Formula: see text]
Study of geometric, electronic structures and vibrations of 4, 4′, 4′′, 4′′′-(porphine-5,10,15,20 tetrayl) tetrakis (benzene sulfonic acid) compound by computational and experimental techniques
Authors: Kaur Prabhjot
Published: March 2021

The optimized geometry and vibrational frequencies of a substituted compound of tetraphenylporphine namely 4, 4[Formula: see text], 4[Formula: see text], 4[Formula: see text]-(porphine-5,10,15,20 tetrayl) tetrakis (benzene sulfonic acid) have been investigated using density functional theory. The vibrational spectra of tetraphenylporphine and its substituted complex were simulated to study the substitution effects of sulfonic acid group at the peripheral sites of tetraphenylporphine. Experimentally, vibrational properties of these molecules have been studied using infrared absorption spectroscopic technique. The vibrational frequencies obtained from the theoretical studies generally agree with the experimental values. For substituted molecules, due to a change in charge distribution, ring vibrations accompanied by the S–O motions also appear at the higher wavenumbers. In the lower region, C–H bending vibrations diminish and SO3 group vibrations arise. The electronic absorption spectra of the substituted tetraphenylporphine in different solvents have been studied using UV-vis spectroscopy. In addition to dipole-dipole and electrostatic interactions, hydrogen bonding plays a key role in molecular-solvent interactions. The energy gap between the highest occupied and lowest unoccupied molecular orbitals and natural bonding orbital analysis show the intermolecular charge transfer interactions. The molecular electrostatic potential and solvent accessible surface area analysis were made in order to study the interaction sites of the molecules. The current-voltage characteristics for the substituted molecule were also plotted. It was found that substituted tetraphenylporphine show good photoconductivity.
China, Japan and India: Asia’s Tangled Triangle in a Disrupted World
Authors: JAIN Purnendra
Published: March 2021

China, Japan and India are overwhelming forces in world politics because of their large population, economic size and trade volume, strategic weight, potential for further technological advancement, economic growth, diplomatic heft and military power. Together they could be an unmatched global force, act as a catalyst to the much touted “Asian century” prospect and help redesign the existing international order to reflect power shift. Yet their relationship to each other is highly complex, and their world views on key issues and strategies of global interaction diverge significantly. Such an unhealthy politico-strategic landscape of the Asian continent is likely to continue. While these three recalibrate and redesign their relations to each other, other regional nations will need to carefully work around this tangled triangle.
South Korea: Emerging Stronger from COVID-19
Authors: RYU Yongwook
Published: March 2021

South Korea’s management of the COVID-19 outbreak and its economic fallout has been largely effective. The challenges are procurement of vaccinations and addressing rising socio-economic inequalities. In addition, the Moon Jae-in administration has to stabilise domestic politics to achieve greater harmony in a highly polarised society and improve Korea’s relationships with the United States, China, Japan and North Korea, which have been stalled in one way or another. If managed well, Korea will emerge stronger from COVID-19 and consolidate its international status as a high-tech, advanced economy.
A conversation with Xiaokui Shu
Authors: Anjum Bushra
Published: March 2021

In this interview, Bushra Anjum, senior editor Ubiquity, sits down with Xiaokui Shu, a Research Staff Member at IBM, and they chat about the latest emerging issues in cybersecurity. Is it possible to discover modern cyber threats before attackers accomplish their goals? The discussion then turns to the new era of dynamic cyber defense, which consists of detection strategies and procedures developed on the fly by security analysts based on live observations.
Designing multisensory experiences for users with different reading abilities visiting a museum
Authors: Soares Guedes Leandro
Published: March 2021

My work explores how technology can support different forms of reading and sense-making of text and multimedia content before, during, and after a museum visit. This paper will present AIMuseum, our pilot study, and how I plan my research. My main contribution is planned to be on the design, implementation, and evaluation of tools to support reading while catering for different abilities.
AI assistive technology for extending sighted guiding
Authors: Vincenzi Beatrice
Published: March 2021

Prior work on AI-enabled assistive technology (AT) for people with visual impairments (VI) has treated navigation largely as an independent activity. Consequently, much effort has focused on providing individual users with wayfinding details about the environment, including information on distances, proximity, obstacles, and landmarks. However, independence is also achieved by people with VI through interacting with others, such as through sighted guiding in navigation. Drawing on the concept of interdependence, this research aims to (1) present an exemplary case of interdependence and draw out important implications for designing AI-enabled AT; (2) propose and evaluate a prototype that enhances social interactions in sighted guiding and aids navigation.
From the Editor: The (Unwired) World at Your Fingertips
Authors: Rajeshwar Krishnan
Published: March 2021

Thanks to digital technologies, the consumer electronics world is rapidly inter-connecting and converging, and combinations of seemingly unrelated products (think cell phone and TV) are on the horizon. The cell phone marketplace is embracing this convergence most emphatically, adding cameras, music players, e-mail, and video/internet access to the cell phone.
From the Editor: On Sports, Science, and Cars
Authors: Rajeshwar Krishnan
Published: March 2021

A visit to historical sites (e.g., the Acropolis in Athens, the Coliseum in Rome) would quickly remind us that athletic pursuits and spectator sports held an exalted place in ancient culture. The gladiators in Roman times, from all accounts, led a good life and were revered for their physical prowess. It is not very different today.
Batteries: Bright Future for an Old Invention
Authors: Scherson Daniel A.
Published: March 2021

Batteries are perhaps the most ubiquitous electrical devices ever invented. Despite their two-century history, batteries have gained over the last decade an ever more important role as the power behind the explosion of the portable electronics market, including computers, cell phones, and entertainment.
Silicon: A Child of Revolution
Authors: Cahn Robert W.
Published: March 2021

Antoine Lavoisier, the pioneering French chemist who (together with Joseph Priestley in England) identified oxygen as an element and gave it its name, in 1789 suggested that quartz was probably a compound of oxygen with an as-yet undiscovered but presumably very common element.
The Chalkboard: Silicon Complementary Metal-Oxide-Semiconductor Field-Effect Transistor
Authors: Tao Meng , Wallace Robert W. , Cleavelin C. Rinn , Wise Rick L.
Published: March 2021

The metal-oxide-semiconductor field-effect transistor (MOSFET or more often MOS) is the most prolific semiconductor device in this information age. Each computer chip contains millions of MOSFETs. Large numbers of MOSFETs are also found in almost all modern consumer products: television sets, cellular phones, automobiles, MP3 players, etc.
Silicon Surface and Interface Issues for Nanoelectronics
Authors: Chabal Yves J. , Feldman Leonard C.
Published: March 2021

To a large extent, the silicon revolution is based on the wonderful properties of the silicon/silicon dioxide interface. The importance of this structure has been documented and cited in many articles and books on the history of technology.
PEM Fuel Cell Catalysts: Cost, Performance, and Durability
Authors: He Chunzhi , Desai Sanket , Brown Garth , Bolleplli Srinivas
Published: March 2021

Proton exchange membrane (PEM) fuel cells are typically classified as methanol-based or hydrogen-based depending on the fuel used to convert chemical energy into electricity. Although direct methanol fuel cells have advantages of fuel availability and storage, long unsolved problems of poor anode kinetics and high methanol crossover limit their potential use mainly to applications with low power requirements, such as portable appliances.
The Role of Silicon Interstitials in Arsenic-Doped Ultrashallow Junction Formation
Authors: Harrison Scott A.
Published: March 2021

The 2005 F. M. Becket Summer Research Fellowship Summary Report
Taking Silicon to the Limit: Challenges and Opportunities
Authors: King Tsu-Jae
Published: March 2021

Silicon-based CMOS transistors can be scaled well into the sub-10 nm regime. However, new materials and processes, in conjunction with advanced transistor structures, will be needed for nanometer-scale MOSFETs to meet performance specifications in the International Technology Roadmap for Semiconductors (ITRS). This paper discusses challenges for achieving target performance metrics at the end of the Roadmap, and approaches to overcoming them.
CMOL: A Silicon-Based Bottom-Up Approach to Nanoelectronics
Authors: Likharev Konstantin K.
Published: March 2021

The current VLSI paradigm based on a combination of lithographic patterning, CMOS circuits, and Boolean logic (outlined in the first part of this article), can hardly be extended into a-few-nm region. The main reason is that at physical gate lengths below 10 nm, the sensitivity of parameters (most importantly, the gate voltage threshold) of silicon field-effect transistors to inevitable fluctuations in fabrication process parameters increases exponentially.
Implications of preexisting asthma on COVID-19 pathogenesis
Authors: Ramakrishnan Rakhee K. , Al Heialy Saba , Hamid Qutayba
Published: March 2021

The coronavirus disease 2019 (COVID-19) pandemic spreading at an alarming rate has taken a heavy toll on the public healthcare systems and economies worldwide. An abnormal and overactivated inflammatory response is occasionally elicited by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and this hyperinflammation is associated with worse prognosis of COVID-19. Theoretically, one would expect patients with asthma to be at a greater risk of SARS-CoV-2 infection considering their increased susceptibility to common respiratory virus-associated exacerbations. Surprisingly, current data do not consistently suggest an increased prevalence of asthma among patients with COVID-19. Considering the high global prevalence of asthma, the characteristics of the disease and/or their conventional therapy might play a role in their potential defense against COVID-19. This may be attributed to the T helper type 2 immune response predominantly seen in patients with asthma. Likewise, asthma therapeutics, including corticosteroids and biologics, may in fact benefit the patients with asthma by alleviating the development of hyperinflammation. On the other hand, elevated IL-17 levels are characteristically seen in a subset of asthma patients with severe disease as well as in patients with COVID-19. Targeting the IL-17 pathway as a treatment strategy could plausibly alleviate acute respiratory distress syndrome (ARDS) in patients with COVID-19 and asthma demonstrating a predominant T helper type 17 response. A clinical trial including a drug targeting this pathway may thus, constitute a logical addition to the global pursuit for effective therapeutics against COVID-19. The complex interplay between the asthma endotypes and COVID-19 is not very well understood and will be discussed in this mini-review.