bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcutaneous vagus nerve stimulation in erosive hand osteoarthritis: protocol for the randomised, double-blind, sham-controlled ESTIVAL trial
Authors: Courties Alice , Deprouw Camille , Rousseau Alexandra , Berard Laurence , Touati Amel , Kalsch Johanna , Villevieille Margaux , Maheu Emmanuel , Miquel Anne , Simon Tabassome , Berenbaum Francis , Sellam Jeremie
Published: November 2022

Introduction

Patients with erosive hand osteoarthritis (EHOA) experience pain and inflammation, two features that can be targeted by vagus nerve stimulation using electrical auricular transcutaneous vagus nerve stimulation (tVNS). A pilot study demonstrated the feasibility of the procedure, so we designed a randomised sham-controlled trial to determine the safety and efficacy of tVNS in EHOA.

Methods and analysis

ESTIVAL Study (Essai randomisé comparant la STImulation auriculaire transcutanée du nerf Vague versus sham stimulation dans l’Arthrose DigitaLe Érosive symptomatique et inflammatoire) is a superiority, randomised, double-blind sham-controlled trial comparing two parallel arms: active and sham tVNSs in a 1:1 ratio. Patients with symptomatic EHOA (score ≥40/100 mm on a visual analogue scale (VAS) for pain of 0–100 mm) and inflammatory EHOA (≥1 clinical and ultrasonography-determined interphalangeal synovitis) are included in 18 hospital centres (17 rheumatology and 1 rehabilitation departments) in France. Active and sham tVNSs use an auricular electrode connected to the Vagustim device, with no electric current delivered in the sham group. Patients undergo stimulation for 20 min/day for 12 weeks. The follow-up visits take place at weeks 4, 8 and 12. The enrolment duration is 2 years and started in April 2021; 156 patients are scheduled to be included. The primary outcome is the difference in self-reported hand pain in the previous 48 hours measured on a VAS of 0–100 mm between baseline and week 12. Secondary outcomes include other pain outcomes, function, quality of life, serum biomarker levels, compliance and tolerance. For a subset of patients, MRI of the hand is performed at baseline and week 12 to compare the change in Outcome Measures in Rheumatology/Hand Osteoarthritis MRI Scoring System subscores. The primary analysis will be performed at the end of the study according to the intent-to-treat principle.

Ethics and dissemination

Ethics approval was obtained from the institutional review board (Comité de Protection des Personnes, 2020-A02213-36). All participants will be required to provide written informed consent. The findings will be published in peer-reviewed journals.

Trial registration number

NCT04520516; Pre-results.

Protocol version and number

V.2 of 11 March 2021.
Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists
Authors: Ashford Polly-Anna , Knight Clare , Heslin Margaret , Clark Allan B , Kanaan Mona , Patel Ushma , Stuart Freya , Kabir Thomas , Grey Nick , Murray Hannah , Hodgekins J , Reeve Nesta , Marshall Nicola , Painter Michelle , Clarke James , Russo Debra , Stochl Jan , Leathersich Maria , Pond Martin , Fowler David , French Paul , Swart Ann Marie , Dixon-Woods Mary , Byford Sarah , Jones Peter B , Perez Jesus
Published: November 2022

Introduction

At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap.

Methods and analysis

This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56–80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT serviceandhave PE according to the Community Assessment of Psychic Experiences—Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery.

Ethics and dissemination

The study received the following approvals: South Central—Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers.

Trial registration number

NCT93895792.
Impact of the SGLT2 inhibitor empagliflozin on urinary supersaturations in kidney stone formers (SWEETSTONE trial): protocol for a randomised, double-blind, placebo-controlled cross-over trial
Authors: Schietzel Simeon , Bally Lia , Cereghetti Grazia Maria , Faller Nicolas , Moor Matthias B , Vogt Bruno , Rintelen Felix , Trelle S , Fuster Daniel
Published: November 2022

Introduction

Kidney stones are a global healthcare problem. Given high recurrence rates and the morbidity associated with symptomatic stone disease, effective medical prophylaxis is clearly an unmet need. Explanatory analyses of randomised controlled trials with sodium/glucose cotransporter isoform 2 inhibitors indicated a 30%–50% reduced rate of stone events in patients with diabetes. Underlying mechanisms remain unclear. We aim to determine the effect of empagliflozin on urinary supersaturations in non-diabetic kidney stone formers to evaluate their therapeutic potential for recurrence prevention. We will provide first clinical trial evidence on whether urinary supersaturations are affected by empagliflozin in kidney stone formers.

Methods and analysis

The SWEETSTONE trial is a randomised, double-blind, placebo-controlled, cross-over, exploratory study to assess the impact of empagliflozin on urinary supersaturations of calcium oxalate, calcium phosphate and uric acid in kidney stone formers. We plan to include 46 non-diabetic adults (18–74 years) with ≥1 past kidney stone event and stone composition with ≥80% of calcium or ≥80% of uric acid. Patients with secondary causes of kidney stones or chronic kidney disease will be excluded. Eligible individuals will be randomised in equal proportions to receive either a 14-day treatment with 25 mg empagliflozin followed after the 2–6 weeks wash out period by a 14-day treatment with a matching placebo or the reverse procedure. Secondary outcomes will include electrolyte concentrations, renal function, mineral metabolism and glycaemic parameters, urinary volume and safety.

Results will be presented as effect measures (95% CIs) with p values and hypothesis testing for primary outcomes (significance level 0.02).

Ethics and dissemination

The SWEETSTONE trial was approved by the Swiss ethics committee and Swissmedic. First results are expected in the fourth quarter of 2022.

Trial registration number

NCT04911660
; Pre-results.
Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial
Authors: Peiris Rachel Grace , Ross Heather , Chan Christopher T , Poon Stephanie , Auguste Bourne Lewis , Rac Valeria E , Farkouh Michael , McDonald Michael , Kaczorowski Janusz , Code Jillianne , Duero Posada Juan , Ong Stephanie , Kobulnik Jeremy , Tomlinson George , Huszti Ella , Arcand JoAnne , Thomas Scott G , Akbari Ayub , Maunder Robert , Grover Steven , Seto Emily , Simard Anne , Pope Brad , Bains Marc , McIntyre Carmen , Torbay Chris , Syed Fatima , Nolan Robert P
Published: November 2022

Introduction

Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE–vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self–care materials, and health-related quality of life.

Methods and analysis

Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes.

Ethics and dissemination

The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care.

Trial registration number

NCT04966104
Cost-effectiveness of internet-delivered cognitive behavioural therapy in patients with cardiovascular disease and depressive symptoms: secondary analysis of an RCT
Authors: Mourad Ghassan , Lundgren Johan , Andersson Gerhard , Husberg Magnus , Johansson Peter
Published: November 2022

Introduction

Cost-effectiveness evaluations of psychological interventions, such as internet-delivered cognitive behavioural therapy (iCBT) programmes, in patients with cardiovascular disease (CVD) are rare. We recently reported moderate to large effect sizes on depressive symptoms in CVD outpatients following a 9-week iCBT programme compared with an online discussion forum (ODF), in favour of iCBT. In this paper, we evaluate the cost-effectiveness of this intervention.

Methods

Cost-effectiveness analysis of a randomised controlled trial. The EQ-5D-3L was used to calculate quality-adjusted life-years (QALYs). Data on healthcare costs were retrieved from healthcare registries.

Results

At 12-month follow-up, the QALY was significantly higher in iCBT compared with the ODF group (0.713 vs 0.598, p=0.007). The mean difference of 0.115 corresponds with 42 extra days in best imaginable health status in favour of the iCBT group over the course of 1 year. Incremental cost-effectiveness ratio (ICER) for iCBT versus ODF was €18 865 per QALY saved. The cost-effectiveness plane indicated that iCBT is a cheaper and more effective intervention in 24.5% of the cases, and in 75% a costlier and more effective intervention than ODF. Only in about 0.5% of the cases, there was an indication of a costlier, but less effective intervention compared with ODF.

Conclusions

The ICER of €18 865 was lower than the cost-effectiveness threshold range of €23 400–€35 100 as proposed by the NICE guidelines, suggesting that the iCBT treatment of depressive symptoms in patients with CVD is cost-effective.

Trial registration number

NCT02778074; Post-results.
PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging
Authors: Huang Yen-Chu , Chang Chia-Hao , Tsai Yuan-Hsiung , Weng Hsu-Huei , Lin Leng-Chieh , Lee Jiann-Der
Published: November 2022

Introduction

Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin–kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis.

Methods and analysis

In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40–80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan.

Ethics and dissemination

This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles.

Trial registration number

ClinicalTrials.gov, Identifier:NCT05001984; Pre-results.
Participant engagement in a community health worker-delivered intervention and type 2 diabetes clinical outcomes: a quasiexperimental study in MexicanAmericans
Authors: Reininger Belinda M , Lopez Juliana , Zolezzi Maria , Lee MinJae , Mitchell-Bennett Lisa A , Xu Tianlin , Park Soo Kyung , Saldana Mayra V , Perez LuBeth , Payne Lisa Y , Collier Cindy , McCormick Joseph B
Published: November 2022

Objectives

This study helps to fill the existing research gap related to participant engagement in behavioural interventions and diabetes management. We examined type 2 diabetes control over time among Mexican Americans by level of engagement in a chronic care management (CCM) program that included community health worker (CHW)-delivered multilevel interventions. The programme complemented clinical care and promoted behaviour changes to improve diabetes self-management.

Design

Quasiexperimental study.

Setting

The study was implemented in the Rio Grande Valley region in the USA. Recruitment was conducted in clinics and community events. All other visits were provided in participant homes and community locations.

Participants

5649 adults (aged ≥18 years) with poorly controlled type 2 diabetes who enrolled in a community-delivered CCM programme between September 2013 and 2018.

Interventions

The intervention comprised two components: CHW home visits conducted every 3 months and diabetes self-management education (DSME) classes provided in community locations.

Primary outcome measures

The primary outcome was haemoglobin A1c (HbA1c) measured at baseline every 3 months for up to 24 months. We first examined changes in HbA1c levels over time. The number of completed CHW and DSME encounters was used to classify participants into engagement groups—high engagement defined as ≥10 encounters (n=2952); low engagement defined as 1–9 encounters (n=2697). We used univariable and multivariable longitudinal linear regression models with a generalised estimating equation method. We tested interactions between engagement groups and time.

Results

Participants’ mean HbA1c decreased from 10.20% at baseline to 8.93% (p<0.0001) at 3 months, remaining stable thereafter. Changes in HbA1c were statistically different between the engagement groups. High engagement participants had lower HbA1c levels over the first 15 months of the follow-up period compared with low engagement participants, as compared at 3 months (−0.44%, 95% CI −0.57% to –0.31%; p<0.0001), 6 months (−0.31%, 95% CI −0.43% to –0.14%; p<0.0001), 9 months (−0.27%, 95% CI −0.42% to –0.13%; p=0.0001), 12 months (−0.23%, 95% CI −0.37% to –0.08%; p=0.0025) and 15 months (−0.32%, 95% CI −0.54% to –0.10%; p=0.0040). At months 18, 21 and 24, the HbA1c differences were not statistically significant (18 months: −0.34%, 95% CI −0.77% to 0.08%; p=0.1086; 21 months: −0.22%, 95% CI −1.00% to 0.56%; p=0.5721; 24 months: −0.42%, 95% CI −1.38% to 0.55%; p=0.3966).

Conclusions

Higher engagement in the CCM programme delivered by CHWs and coordinated with clinical care was associated with beneficial improvements in type 2 diabetes control, but both engagement groups showed strong improvements.
Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study
Authors: Ghossein-Doha Chahinda , Wintjens Marieke S J N , Janssen Emma B N J , Klein Dorthe , Heemskerk Stella C M , Asselbergs Folkert W , Birnie Erwin , Bonsel Gouke J , van Bussel Bas C T , Cals Jochen W L , Ten Cate Hugo , Haagsma Juanita , Hemmen Bena , van der Horst Iwan C C , Kietselaer Bastiaan L J H , Klok Frederikus A , de Kruif Martijn D , Linschoten Marijke , van Santen Susanne , Vernooy Kevin , Willems Loes H , Westerborg Rosa , Warle Michiel , van Kuijk Sander M J
Published: November 2022

Introduction

The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

Methods and analysis

Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

Ethics and dissemination

Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

Trial registration number

NCT05240742.
Melatonin for sleep disorders in children with neurodevelopmental disorders: protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials
Authors: Jørgensen Caroline Kamp , Hermann Rikke , Juul Sophie , Faltermeier Pascal , Horowitz Mark , Moncrieff Joanna , Gluud Christian , Jakobsen Janus Christian
Published: November 2022

Introduction

Neurodevelopmental disorders are a group of disorders thought to be associated with the functioning of the brain and the nervous system. Children with neurodevelopmental disorders often have sleep-related comorbidities that may negatively affect quality of life for both the children and their families. Melatonin is one of the most used interventions in children with neurodevelopmental disorders and sleep disorders. Previous reviews have investigated the effects of melatonin for sleep disorders in children with neurodevelopmental disorders, but these had important limitations, such as inadequate analysis of adverse effects, small sample sizes and short follow-up.

Methods and analysis

This is a protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. The protocol is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will search for published and unpublished trials in the Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, PsycINFO, ClinicalTrials.gov and the International Clinical Trials Registry Platform. We will search the databases from their inception without language restrictions. We will also request clinical study reports from regulatory authorities and pharmaceutical companies. Review authors working in pairs will screen reports, extract data and conduct risk of bias assessments using the Cochrane Risk of Bias tool. We will include randomised clinical trials comparing melatonin versus placebo or no intervention for sleep disorders in children with neurodevelopmental disorders. Primary outcomes will be total sleep time and adverse effects. Secondary outcomes will be quality of life of the child and caregivers and sleep onset latency. Data will be analysed using random-effects and fixed-effect meta-analyses. Certainty of evidence will be assessed with Grading of Recommendations, Assessment, Development and Evaluation approach.

Ethics and dissemination

Ethical approval was not required for this protocol. The systematic review will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42022337530.
Agile development of a digital exposure treatment for youth with chronic musculoskeletal pain: protocol of a user-centred design approach and examination of feasibility and preliminary efficacy
Authors: Harrison Lauren E , Webster Sarah N , Van Orden Amanda R , Choate Ellison , Jehl Nicole , Stinson Jennifer , Wicksell Rikard K , Darnall Beth D , Simons Laura E
Published: November 2022

Introduction

Chronic pain affects a significant number of children and impacts multiple domains including social, emotional and behavioural functioning, and negatively impacts family functioning. Roughly 5% of youth with chronic pain experience moderate to severe pain-related disability, with pain-related fear and avoidance of activities being identified as substantial barriers to treatment engagement. Evidence supports targeted psychological and physical interventions to address these barriers (eg, graded-exposure treatment), but accessibility to intervention is undermined by a shortage of services outside of urban areas, high treatment-related costs, and long provider waitlists; highlighting the need to develop digitally delivered behavioural intervention, using agile and iterative study designs that support rapid development and timely dissemination.

Methods and analysis

This study seeks to develop an effective and scalable intervention for youth with chronic pain and their caregivers. This paper presents a user-centred protocol for the development and refinement of a digital exposure treatment for youth and caregivers, as well as the study design to examine feasibility and preliminary efficacy of the treatment using single-case experimental design (SCED). Assessments include daily diaries, completed from baseline and daily throughout the intervention (~6 weeks), and at 3-month follow-up, as well as self-report measures completed at baseline, end of intervention and 3-month follow-up. Primary outcomes include treatment satisfaction, treatment expectancy, adherence to daily dairies and functional disability. Secondary outcomes are pain-related fear and avoidance of activities, pain catastrophising and pain acceptance. We will present descriptive and model-based inference analyses, based on SCED reporting guidelines. We will calculate effect sizes for each individual on each outcome. We will examine mean treatment expectancy, credibility and satisfaction scores, and patient drop-out percentage.

Ethics and dissemination

This study is approved by the Institutional Review Board at Stanford University (protocol #53323). Findings will be actively disseminated through peer-reviewed journals, conference presentations and social media.

Trial registration number

NCT05079984.
Psychopathology in mothers of children with pathogenic Copy Number Variants
Authors: Niarchou Maria , Cunningham Adam C. , Chawner Samuel J. R. A. , Moulding Hayley , Sopp Matthew ,   IMAGINE-ID, Hall Jeremy , Owen Michael J. , van den Bree Marianne B.M.
Published: November 2022

Background

Caring for children with pathogenic neurodevelopmental Copy Number Variants (CNVs) (ie, deletions and duplications of genetic material) can place a considerable burden on parents and their quality of life. Our study is the first to examine the frequency of psychiatric diagnoses in mothers of children with CNVs compared with the frequency of psychiatric problems in age-matched mothers from a large community study.

Methods

Case–control study. 268 mothers of children with a CNV diagnosed in a medical genetics clinic and 2680 age-matched mothers taking part in the Avon Longitudinal Study of Parents and Children study.

Results

Mothers of children with CNVs reported higher frequency of depression, anorexia, bulimia, alcohol abuse and drug addiction problems compared with the age-matched mothers from the community sample. Focusing on psychiatric problems arising immediately after the birth of the index child, we found that the levels of depression symptoms were similar between the two groups (48% in mothers of children with CNVs vs 44% in mothers of the community sample, p=0.43), but mothers of children with CNVs had higher frequency of anxiety symptoms (55%) compared with mothers from the community sample (30%, p=0.03).

Conclusion

Our study highlights the need for healthcare providers to devise treatment plans that not only focus on meeting the child’s needs but also assess and, if needed, address the mental health needs of the parent.
Symptom clusters in oncology outpatients: stability and consistency across a cycle of chemotherapy
Authors: Harris Carolyn S , Kober Kord , Cooper Bruce , Conley Yvette P , Hammer Marilyn J , Dhruva Anand A , Cartwright Frances , Paul Steven , Levine Jon , Miaskowski Christine
Published: November 2022

Objectives

Improved understanding of the stability and consistency of symptom clusters across time, symptom dimensions and cancer diagnoses will lead to refinements in symptom assessments and management, and provide direction for mechanistic studies. Study purposes were to describe the occurrence, severity and distress of 38 symptoms; evaluate the stability and consistency of symptom clusters across a cycle of chemotherapy, three symptom dimensions and four distinct cancer types; and identify common and distinct symptom clusters.

Methods

Oncology outpatients (n=1329) completed the Memorial Symptom Assessment Scale prior to their next cycle of chemotherapy (T1), 1 week after chemotherapy (T2) and 2 weeks after chemotherapy (T3). Symptom clusters were identified using exploratory factor analysis using unweighted least squares. GEOMIN rotated factor loadings with absolute values ≥0.40 were considered meaningful. Clusters were stable if they were identified across each time point and/or dimension. Clusters were consistent if the same two or three symptoms with the highest factor loadings were identified across each time point and/or dimension.

Results

Patients reported 13.9 (±7.2) symptoms at T1, 14.0 (±7.0) at T2 and 12.2 (±6.8) at T3. Psychological, weight gain, gastrointestinal and respiratory clusters were stable across time and dimensions. Only the psychological, weight gain and respiratory clusters were consistent across time and dimensions.

Conclusion

Given the stability of the psychological, weight gain and gastrointestinal clusters across cancer diagnoses, symptoms within these clusters need to be routinely assessed. However, respiratory and hormonal clusters are unique to specific cancer types and the symptoms within these clusters are variable.
Particle production in a hybrid approach for a beam energy scan of Au+Au/Pb+Pb collisions between $$\sqrt{s_\textrm{NN}}$$ = 4.3 GeV and $$\sqrt{s_\textrm{NN}}$$ = 200.0 GeV
Authors: Schäfer Anna , Karpenko Iurii , Wu Xiang-Yu , Hammelmann Jan , Elfner Hannah
Published: November 2022

Heavy-ion collisions at varying collision energies provide access to different regions of the QCD phase diagram. In particular collisions at intermediate energies are promising candidates to experimentally identify the postulated first order phase transition and critical end point. While heavy-ion collisions at low and high collision energies are theoretically well described by transport approaches and hydrodynamics+transport hybrid approaches, respectively, intermediate energy collisions remain a challenge. In this work, a modular hybrid approach, the coupling 3+1D viscous hydrodynamics () to hadronic transport (), is introduced. It is validated and subsequently applied in Au+Au/Pb+Pb collisions between $$\sqrt{s_\textrm{NN}}$$

s
NN

= 4.3 GeV and $$\sqrt{s_\textrm{NN}}$$

s
NN

= 200.0 GeV to study the rapidity and transverse mass distributions of identified particles as well as excitation functions for $$\textrm{dN}/\textrm{d}y|_{y = 0}$$

dN
/
d
y
|

y
=
0

and $$\langle p_\textrm{T} \rangle $$

⟨

p
T

⟩

. A good agreement with experimental measurements is obtained, including the baryon stopping dynamics. The transition from a Gaussian rapidity spectrum of protons at lower energies to the double-hump structure at high energies is reproduced. The centrality and energy dependence of charged particle $$v_2$$

v
2

is also described reasonably well. This work serves as a basis for further studies, e.g. systematic investigations of different equations of state or transport coefficients.
Scotogenic Dirac neutrino mass models embedded with leptoquarks: one pathway to address the flavor anomalies and the neutrino masses together
Authors: Li Shao-Ping , Li Xin-Qiang , Yan Xin-Shuai , Yang Ya-Dong
Published: November 2022

If the leptoquarks proposed to account for the intriguing anomalies observed in the semileptonic B-meson decays, $$R_{D^{(*)}}$$

R

D

(

∗
)

and $$R_{K^{(*)}}$$

R

K

(

∗
)

, as well as in the anomalous magnetic moment of the muon, $$(g-2)_\mu $$

(
g
-
2
)

μ

, can be embedded into the scotogenic Dirac neutrino mass models, all these flavor anomalies, together with the origin of neutrino masses and the nature of dark matter, could be potentially addressed in a unified picture. Among the minimal seesaw, one-loop, and two-loop realizations of the dimension-4 effective operator $${\mathcal {L}}_{4}$$

L
4

for the Dirac neutrino masses, we show that plenty of diagrams associated with the two-loop realizations of $${\mathcal {L}}_{4}$$

L
4

can support the coexistence of leptoquarks and dark matter candidates. After a simple match of these leptoquarks with the ones introduced to accommodate all the flavor anomalies, we establish the scotogenic Dirac neutrino mass models embedded with leptoquarks, which could address all the problems mentioned above.
Analysis of CKM-favored quasi-two-body $$B \rightarrow D (R\rightarrow ) K \pi $$ decays in PQCD approach
Authors: Zou Zhi-Tian , Fang Wen-Sheng , Liu Xin , Li Ying
Published: November 2022

LHCb Collaboration studied the resonant structure of $$B_s\rightarrow \overline{D}^0K^-\pi ^+$$

B
s

→

D
¯

0

K
-

π
+

decays using the Dalitz plot analysis technique, based on a data sample corresponding to an integrated luminosity of $$3.0\textrm{fb}^{-1}$$

3.0

fb

-
1

of pp collision. The $$K^-\pi ^+$$

K
-

π
+

components have been analyzed in the amplitude model, where the decay amplitude is modeled to be the resonant contributions with respect to the intermediate resonances $$K^*(892)$$

K
∗

(
892
)

, $$K_0^*(1430)$$

K
0
∗

(
1430
)

and $$K_2^*(1430)$$

K
2
∗

(
1430
)

. Motivated by the experimental results, we investigate the CKM-favored quasi-two-body $$B \rightarrow \overline{D}^0K\pi $$

B
→

D
¯

0

K
π

decays in the framework of the perturbative QCD (PQCD) approach. We calculate the the branching fractions by introducing the appropriate wave functions of $$K\pi $$

K
π

pair. Our results are in agreement well the available data, and others can be tested in LHCb and Belle-II experiments. Using the narrow-width-approximation, we also extract the branching fractions of the corresponding two-body $$B\rightarrow {\overline{D}} R$$

B
→

D
¯

R

decays, which agree to the previous theoretical calculations and the experimental data within the errors. There are no CP asymmetries in these decays in the standard model, because these decays are all governed by only the tree operators.
A hybrid physics-informed neural network for nonlinear partial differential equation
Authors: Lv Chunyue , Wang Lei , Xie Chenming
Published: November 2022

The recently developed physics-informed machine learning has made great progress for solving nonlinear partial differential equations (PDEs), however, it may fail to provide reasonable approximations to the PDEs with discontinuous solutions. In this paper, we focus on the discrete time physics-informed neural network (PINN), and propose a hybrid PINN (hPINN) scheme for the nonlinear PDEs. In this approach, the local solution structures are classified as smooth and nonsmooth scales by introducing a discontinuity indicator, and then the automatic differentiation technique is employed for resolving smooth scales, while an improved weighted essentially nonoscillatory (WENO) scheme is adopted to capture discontinuities. We then test the present approach by considering the viscous and inviscid Burgers equations, and it is shown that compared with original discrete time PINN, the present hPINN approach has a better performance in approximating the discontinuous solution even at a relatively larger time step.
160 Gbps capacity and sub-us latency of polarization-independent optical packet switch architecture for free-space optical network using PLZT optical switch
Authors: Meng Jiacheng , Wang Wei , Xie Ningbo , Gao Duorui , Zhu Jiaxuan , Bai Zhaofeng , Xie Xiaoping
Published: November 2022

In this paper, we discuss the challenges and limitations of current free-space optical (FSO) networks toward scaling beyond the 100 Gbps switch capacity era while achieving low-latency and high-reliability. Owing to the slowdown of Moore’s law, to avoid electronically-induced bottlenecks, we construct an FSO switch network and experimentally evaluate the feasibility of ultrafast optical packet switch architecture based on polarization-independent plomb lanthanum zirconate titanate (PLZT) switch without buffering. The bit error ratio of 160 Gbps ([Formula: see text]) data was validated based on measurements while still preserving the sub-us latency metrics ([Formula: see text] ns). The experimental results may offer a significant reference for FSO communication and network.
Mid-crustal reactivation processes linked to frictional melting and deep void development during seismogenic slip: examples from the Lewisian Complex, NW Scotland
Authors: Hardman K. , Holdsworth R. E. , Scott L. , Dempsey E. , McCaffrey K. J. W.
Published: November 2022

Exhumed examples of ancient fault voids formed during seismic slip at depths >10 km are well preserved in the Assynt Terrane of the Lewisian Complex, NW Scotland. They are interpreted to have formed during regional Mesoproterozoic (
c.
1.55 Ga; ‘Assyntian’) strike-slip faulting. Deformation is characterized by sinistral reactivation of pre-existing NW–SE-trending features including intrusive contacts of (
c.
2.4 Ga) mafic dykes and Paleoproterozoic ductile shear zone fabrics (
c.
1.75 Ga). Reactivation occurred at palaeodepths of 10–15 km, where frictional–viscous deformation synchronous with co-seismic frictional melting led to cycles of millimetre- to decimetre-scale cavity dilation and collapse. Although individual melt-generating slip surfaces may have become rapidly welded, faulting was able to repeatedly localize along adjacent pre-existing planar anisotropies favourably oriented for slip, leading to the creation of a mesh of foliation-parallel melt generation surfaces linked by foliation-perpendicular dilational voids. The latter features are filled by chaotic clast-supported wall rock collapse breccias, localized injected frictional melts and hydrothermal mineralization. The fills act as natural props, holding cavities open and preserving them as long-term, pipe-like fluid flow conduits. These exhumed features are likely to be typical of multi-rupture seismogenic fault systems formed by direct reactivation of pre-existing basement structures.
Petrogenesis of the Triassic andesites in the East Kunlun Orogen, East Tethys: implications for crustal maturation within an extensional setting
Authors: Zhao Xu , Fu Lebing , Santosh M. , Wei Junhao , Zhang Cheng , Chen Jiajie , Xu Chongwen , Zhang Xinming
Published: November 2022

The tectonic and crustal evolution of the East Kunlun Orogen in the Triassic remains unclear. We investigated the Triassic andesites (235 and 216 Ma) to investigate these issues. The Mid- and Late Triassic andesites are calc-alkaline with enriched Sr–Nd isotopic compositions: (
87
Sr/
86
Sr)
i
 = 0.709210–0.709758 and

ε

Nd
(
t
) = −8.0 to −6.9. The Mid-Triassic andesites have higher Mg, Cr and Ni contents and more depleted Hf isotopic compositions (

ε

Hf
(
t
) = −4.2 to 1.3) than the Late Triassic andesites (

ε

Hf
(
t
) = −7.4 to −5.8). These features are explained by the derivation of magma from partial melting of the mafic lower continental crust, although minor lithospheric mantle materials are also involved in the Mid-Triassic andesites. The andesites were generated in extensional settings related to slab break-off in the Mid-Triassic and lithospheric delamination in the Late Triassic, respectively. The Late Triassic magmatic suites are higher in K and represent a more mature continental crust, indicating that crustal reworking in extensional settings contributes to crustal maturation. In combination with the regional magmatic, structural and sedimentary records, we propose that the East Kunlun Orogen evolved from oceanic subduction in the Late Permian to Mid-Triassic through continental collision in the Mid-Triassic to post-collision in the Late Triassic.
Chapter 10. Sequence stratigraphy in the exploration for North Sea Jurassic stratigraphic traps
Authors: Copestake Philip
Published: November 2022

The application of sequence stratigraphic concepts and methods significantly enhances the evaluation of stratigraphic traps. In this chapter, five examples of, as yet undrilled, potential UK North Sea Jurassic combination stratigraphic traps, from the East Shetland Platform, South Viking Graben, Inner Moray Firth and Central Graben, are discussed and the potential application of sequence stratigraphic methods in their evaluation considered.
Middle to Late Pennsylvanian tetrapod evolution: the Kasimovian bottleneck
Authors: Lucas Spencer G.
Published: November 2022

The Late Pennsylvanian was a critical juncture in tetrapod evolution when many terrestrially adapted taxa first appeared. The Middle Pennsylvanian (Moscovian) tetrapod record reflects a taphonomic megabias that favoured preservation, discovery and collection of aquatic tetrapods that lived in wetland palaeoenvironments (‘coal swamps’). The Kasimovian tetrapod record is limited to seven localities, all but one in the USA, and two of which are singleton records, so it is less abundant, diverse or widespread than earlier Moscovian and later Gzhelian tetrapod records. This ‘Kasimovian bottleneck’ hinders interpretation of tetrapod evolutionary events across the Middle–Late Pennsylvanian boundary. Significant changes did take place across that boundary, but they were spread out over Moscovian through Gzhelian time. Many of the perceived changes in tetrapods across the Middle–Late Pennsylvanian boundary are largely artefacts of facies changes and the Moscovian tetrapod taphonomic megabias and of the limited fossil record of Kasimovian tetrapods. Therefore, there is no simple link between Late Pennsylvanian tetrapod evolutionary events and changes in climate and vegetation.
IMPRoVED: Integrated Method to Predict PostRouting setup Violations in Early Design Stages
Authors: Krishna Kashyap Suhas , Ozev Sule
Published: November 2022

The detail routing process is by far the most time consuming during the physical design flow. Routing starts with an estimation of timing slacks and aims to meet the timing specifications at signoff. In this paper, we propose an improved method to predict the net delays using RandomForestRegressor and thereby predict critical paths early on at the placement stage. Quick timing prediction is also essential in making time-sensitive edits to stepping of the chip based on post-Si feedback. The proposed algorithm is based on five novel features, namely, targeted feature selection, introduction of a one-hot encoding scheme, an outlier identification method, post-route buffer-bloat prediction, and post-route cell sizing prediction. Experimental results on academic benchmarks and industry circuits, both on advanced 10nm process node show that the proposed algorithm has led to significant improvements in accurately predicting timing slacks when compared with state of the art. The proposed algorithm predicts slack within 0.598% of signoff results, whereas the state of art results are erroneous by an average of 53.33% for the same metric. Overall time savings of 44.1% is seen when compared to running the traditional flow, and savings of 90% is seen for obtaining the timing results.
Symmetric Volume Maps: Order-invariant Volumetric Mesh Correspondence with Free Boundary
Authors: Abulnaga S. Mazdak , Stein Oded , Golland Polina , Solomon Justin
Published: November 2022

Although shape correspondence is a central problem in geometry processing, most methods for this task apply only to two-dimensional surfaces. The neglected task of
volumetric
correspondence—a natural extension relevant to shapes extracted from simulation, medical imaging, and volume rendering—presents unique challenges that do not appear in the two-dimensional case. In this work, we propose a method for mapping between volumes represented as tetrahedral meshes. Our formulation minimizes a distortion energy designed to extract maps symmetrically, i.e., without dependence on the ordering of the source and target domains. We accompany our method with theoretical discussion describing the consequences of this symmetry assumption, leading us to select a symmetrized ARAP energy that favors isometric correspondences. Our final formulation optimizes for near-isometry while matching the boundary. We demonstrate our method on a diverse geometric dataset, producing low-distortion matchings that align closely to the boundary.
Separating Rank Logic from Polynomial Time
Authors: Lichter Moritz
Published: November 2022

In the search for a logic capturing polynomial time the most promising candidates are Choiceless Polynomial Time (CPT) and rank logic. Rank logic extends fixed-point logic with counting by a rank operator over prime fields. We show that the isomorphism problem for CFI graphs over ℤ

2

i

cannot be defined in rank logic, even if the base graph is totally ordered. However, CPT can define this isomorphism problem. We thereby separate rank logic from CPT and in particular from polynomial time.
Noise in Biomolecular Systems: Modeling, Analysis, and Control Implications
Authors: Briat Corentin , Khammash Mustafa
Published: November 2022

While noise is generally associated with uncertainties and often has a negative connotation in engineering, living organisms have evolved to adapt to (and even exploit) such uncertainty to ensure the survival of a species or implement certain functions that would have been difficult or even impossible otherwise. In this article, we review the role and impact of noise in systems and synthetic biology, with a particular emphasis on its role in the genetic control of biological systems, an area we refer to as cybergenetics. The main modeling paradigm is that of stochastic reaction networks, whose applicability goes beyond biology, as these networks can represent any population dynamics system, including ecological, epidemiological, and opinion dynamics networks. We review different ways to mathematically represent these systems, and we notably argue that the concept of ergodicity presents a particularly suitable way to characterize their stability. We then discuss noise-induced properties and show that noise can be both an asset and a nuisance in this setting. Finally, we discuss recent results on (stochastic) cybergenetics and explore their relationships to noise. Along the way, we detail the different technical and biological constraints that need to be respected when designing synthetic biological circuits. Finally, we discuss the concepts, problems, and solutions exposed in the article; raise criticisms and concerns about current ideas and approaches; suggest current (open) problems with potential solutions; and provide some ideas for future research directions.
The State and Trust
Authors: Herreros Francisco
Published: November 2022

This article explores the effects of the state on the creation of social trust. It identifies four theories connecting these two variables. The first and probably most important one stresses the role of the state as a third-party punisher of free-riders, especially in large societies where people have continuous interactions with strangers. The second claims that citizens extrapolate state officers’ corruption levels to ordinary citizens’ trustworthiness. The third claims that the state promotes trust by increasing income equality, and the final one claims that the state fosters trust by providing information about types of people. Finally, the article discusses how the empirical models relating to the state and trust deal with endogeneity problems, how outcomes from experimental analyses question the results obtained from observational data, and how this work affects our ideas about what trust ultimately refers to.