bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of delamination of composite laminates via extended finite element method based on the layerwise displacement theory and cohesive zone method
Authors: Santos Matheus VM , Sartorato Murilo , Roy Anish , Tita Volnei , Ribeiro Marcelo L
Published: October 2021

Composite laminates are being more employed as fundamental structures due to its low weight and high stiffness. To predict the material response in presence of damage can be demanding due to composite’s complex nature. Hence, superior computational models should be further investigated to speculate a more accurate composite behavior. This paper proposes an extended finite element procedure, based on the layerwise displacement theory, to simulate delamination to composite laminate. It is assumed a cohesive behavior to the damaged domain, described by a traction separation law. An extra degree of freedom associated to the strong discontinuity (delamination) is added at each layer top and bottom surface for out-of-plane displacement. This extra degree of freedom is only active on the failed nodes. To validate the model, a pre-delaminated composite analysis is performed and compared to results already reported in the literature. In addition, all stress components can be precisely calculated due to layer wise displacement field assumption, without any concern about the membrane and shear locking, not to mention its greater computational efficiency when compared to equivalent three-dimensional elements. Therefore, in the present work, it is shown the limitations and potentialities when a cohezive formulation is combined to extended finite element method using a new kind of approach. Additionally, this formulation makes easier to model delaminations using finite element method keeping a good accuracy without the need of cumbersome finite element models.
A Controlled Evaluation of a Sport-Specific Performance Optimization Program in an Athlete Diagnosed With Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder Within the Context of COVID-19
Authors: Phrathep Davy , Donohue Brad , Kraus Shane , Paul Michelle , Mercer John
Published: October 2021

Adolescent athletes with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) experience unique challenges that impact their sport performance, such as making errors due to poor concentration. The current multiple-baseline across behaviors case trial (i.e., positive assertion and negative assertion) is an evaluation of The Optimum Performance Program in Sports in an adolescent athlete diagnosed with ADHD and ODD. Intervention skill sets were targeted sequentially in a virtual format to safeguard against COVID-19 contraction. A battery of psychological measures was administered at baseline, post-intervention, and 1-month follow-up. Results indicated negative and positive assertion skills improved, but only when targeted, and severity of ADHD and ODD symptom severity, general mental health symptoms, and factors interfering with sport performance decreased from pre- to post-intervention and these improvements were maintained at 1-month follow-up. Similar improvements occurred in relationships with coaches, teammates, and family. Treatment integrity and consumer satisfaction were high.
Proportion of conflict, contingency learning, and recency effects in a Stroop task
Authors: Jiménez Luis , Gallego David , Agra Oscar , Lorda María José , Méndez Cástor
Published: October 2021

Recent research on the relation between learning and cognitive control has assumed that conflict modulates learning, either by increasing arousal and hence improving learning in high-conflict situations, or by inducing control, and hence inhibiting the processing of distracters and their eventual association with the imperative responses. We analyse whether the amount of conflict, manipulated through the proportion of congruency in a set of Stroop inducer trials, affects learning of contingencies established on diagnostic trials composed by neutral words associated with colour responses. The results reproduced the list-wide proportion of congruency effect on the inducer trials, and showed evidence of contingency learning on the diagnostic trials, but provided no indication that this learning was modulated by the level of conflict. Specific analyses conducted to control for the impact of episodic effects on the expression of learning indicated that contingency effects were not driven by the incremental processes that could be expected by associative learning, but rather they were due to the impact of the most recent trial involving the same distracter. Accordingly, these effects disappeared when tested selectively on trials that required a non-matching response with respect to the previous occurrence of the distracter. We interpret this result in the context of the debate on how learning and memory interact with the processes of cognitive control.
The social structure of 70 years of literature on Human Reliability
Authors: Ramos Marilia A , Patriarca Riccardo , Paltrinieri Nicola
Published: October 2021

From its first applications to the military domain, HRA progressed to applications in Nuclear Power Plants (NPPs) operations, when development and validation of methods mainly targeted their use in Probabilistic Risk Assessments. In recent years, advances in HRA include the extension to various application fields, the development of new methods or enhancement of existing ones, data collection efforts, among others. These advances are possible due to the increasing number of authors on HRA and collaboration between them. Systematic literature reviews have been increasingly used for understanding various aspects of a research field. While recent reviews have provided an overview of the topics addressed by HRA research, the social structure of the field has not yet been fully explored. This paper discusses the social structure of HRA through 70 years of literature. The review aims at responding to how the links between different authors groups were created, that is, which large-scale projects, geographical proximity, or research topics contributed to these connections. The results indicate that (1) while the research on HRA was mostly based in the U.S.A. before 2000, China, Japan, and South Korea are significant contributors to the recent literature; (2) despite the increasing diversity of application fields, such as applications to the maritime and offshore industry, the main focus on NPPs operations is persistent since the 1980s; (3) due to large research projects, favored by a connected world, the physical workspace does not limit current collaboration among authors.
APOL1 genotypes: Do they contribute to ethnicity-associated biological health inequalities in pregnancy?
Authors: Smith Priscilla , Bramham Kate
Published: October 2021

Inferior health outcomes for people of African and Afro-Caribbean ancestry compared to those of European ancestry are well recognised. There is a disproportionate impact within these communities compared to other ethnic groups including pregnancy outcomes, hypertension, kidney disease and diabetes. The ‘Black Lives Matter’ movement has highlighted that it is imperative to examine all factors contributing to this inequity and to strive to explore multifaceted ways, including social, economic, psychological and biological to improve overall health equity. It is within this context that we discuss the novel finding of Apolipoprotein 1 genetic polymorphisms which have been identified in some populations of African ancestry. We will explore the history and evolutionary advantages of Apolipoprotein 1 polymorphisms and the pathophysiology resulting from these adaptations and examine the impact of Apolipoprotein 1 on pregnancy outcomes, the risks and benefits of screening for high-risk Apolipoprotein 1 alleles in black communities and potential treatments currently being investigated.
“Inter and Enter: An Invitation to Collaboration Thru Autoethnography”
Authors: Alexander Bryant K. , Hernandez Carmen G. , Pelias Ronald J. , Alhayek Katty , Poulos Christopher , Moreira Claudio , Sutton Timothy , Stephenson Ayshia , Foster Elissa , Twishime Porntip I.
Published: October 2021

This performative and collaborative autoethnography plays with the homophonic or maybe homiletics of “inter” and “enter” as the invitational aspect of collaborative autoethnography. The contribution of diverse collaborators from differing racial, ethnic, geo-spatial locations, and generational standpoints speak to/between experiences with the dialogic aspects of autoethnography; the speaking of self with and for others that is always a part of autoethnographic practice, now made salient in the intentional collaborative, thus exploring the interpersonal, interracial, international, intersectional, interstitial, and the symbolic interactional aspects of autoethnography.
Cystic Fibrosis Increases Long-Term Revision Rates of Endoscopic Sinus Surgery in Patients With Comorbid Chronic Rhinosinusitis
Authors: Smith Kristine A. , Gill Amarbir S. , Beswick Daniel M. , Meeks Huong , Oakley Gretchen M. , Yim Michael , Curtin Karen , Orlandi Richard R. , Alt Jeremiah A.
Published: October 2021

Background: Comorbid chronic rhinosinusitis (CRS) of adulthood is increasing among patients with cystic fibrosis (CF) due to improved median survival. However, little is known about the natural history of endoscopic sinus surgery (ESS) in this cohort. The objective of this study was to evaluate the revision rate of ESS and associated risk factors among adults with CRS and CF (CRSwCF). Methods: The Utah Population Database was queried for patients age >18 with CRS who underwent at least one ESS between 1996 and 2018. Demographic information and ESS history were collected and compared for CRSwCF versus CRS without CF (CRSsCF) using chi-square and t-tests. Risk factors for revision were analyzed using Cox proportional hazard models and logistic regression analysis. Results: A total of 34 050 patients (33 639 CRSsCF and 411 CRSwCF) were included in the final analysis. The mean duration of follow-up was 9.3 and 9.3 years, respectively ( P = .98). Adult patients with CF were significantly more likely to undergo revision ESS (18.7%) than those without CF (13.4%; P < .01). Logistic regression analysis indicated that a diagnosis of CF independently elevated the risk for revision ESS in the absence of nasal polyps (odds ratio [OR] 2.18, confidence interval [CI] 1.34-3.54), asthma (OR 1.36, CI 0.94-1.98), and allergies (OR 1.29, CI 0.90-1.73). Conclusion: In the era before highly effective modulator therapies, the mean revision rate of ESS among adults with CRSwCF was 18.7%, significantly greater than that of adults with CRSsCF. CF was an independent risk factor for revision ESS in the absence of nasal polyps, asthma, and allergies.
Development and Cultural Adaptation of a Computer-Delivered and Multi-Component Alcohol Reduction Intervention for Russian Women Living with HIV and HCV
Authors: Brown Jennifer L. , Anastasakis Iakovos , Revzina Natalia , Capasso Ariadna , Boeva Ekaterina , Rassokhin Vadim , Crusey Adrienne , Sales Jessica M. , Hitch Anthony , Renfro Tiffaney , DiClemente Ralph J.
Published: October 2021

Background:

There is elevated prevalence of problem drinking among Russian women living with HIV and HCV co-infection. This paper describes the development and cultural adaptation of a multi-component alcohol reduction intervention incorporating a brief, computer-delivered module for Russian women living with HIV and HCV co-infection.

Methods:

The format and content of the intervention were adapted to be linguistic-, cultural-, and gender-appropriate using the ADAPT-ITT framework. A computer-delivered module and brief clinician-delivered individual and telephone sessions were developed.

Results:

We describe the theoretical foundations of the intervention, the cultural adaptation of the intervention, and overview the content of the intervention’s multiple components.

Discussion:

Interventions to reduce alcohol use that can be integrated within Russian HIV treatment centers are urgently needed. If efficacious, the culturally-adapted intervention offers the promise of a cost-effective, easily disseminated intervention approach for Russian women living with HIV/HCV co-infection engaging in problematic alcohol use.
Comparing the Efficacy of Postoperative Pain Control Between Intravenous Parecoxib and Oral Diclofenac in ACL Reconstruction
Authors: Chuaychoosakoon Chaiwat , Parinyakhup Wachiraphan , Wiwatboworn Arnan , Purngpiputtrakul Peeranut , Wanasitchaiwat Pawin , Boonriong Tanarat
Published: October 2021

Background:

A nonsteroidal anti-inflammatory drug such as oral diclofenac is normally used to relieve postoperative pain after anterior cruciate ligament reconstruction (ACLR), but most patients continue to have moderate-to-severe pain that disturbs their rehabilitation. Some orthopaedists prefer to use intravenous (IV) parecoxib for postoperative pain control.

Purpose:

To compare the efficacy of IV parecoxib and oral diclofenac for postoperative pain control in ACLR.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

We retrospectively collected and analyzed postoperative pain in patients who underwent both single- and double-bundle ACLR; pain was reported on a 10-point visual analog scale (VAS; 10 = worst pain). After the operation, each patient was given either IV parecoxib twice a day or oral diclofenac 3 times a day, and all patients received paracetamol 6 times per day for 24 hours postoperatively. If the patient complained of moderate or severe pain (VAS >3) after surgery, 3 mg of morphine would be given intravenously every 3 hours and 1 mg of morphine as a rescue analgesic every 1 hour for 24 hours postoperatively. Postoperative VAS and morphine consumption were recorded every 4 hours for 24 hours. Data were analyzed using paired t test, analysis of variance, and chi-square test.

Results:

Overall, 161 patients were included in this study, of whom 47 received IV parecoxib and 114 received oral diclofenac. The mean VAS scores at 4 and 8 hours postoperatively were 3.5 and 3.4, respectively, in the parecoxib group, and 4.4 and 4.7, respectively, in the diclofenac group. The parecoxib group had significantly lower mean VAS than the diclofenac group at 4 hours ( P = .047) and 8 hours ( P = .005), and the mean cumulative morphine consumption in the parecoxib group was significantly lower than in the diclofenac group at all time points ( P < .05) except 4 hours postoperatively.

Conclusion:

This study found that IV parecoxib was more effective than oral diclofenac in controlling postoperative pain and resulted in lower postoperative morphine consumption within the first 24 hours after ACLR.
Bringing Donors Along on the Journey: A Preliminary Investigation of Organisational Strategies in Transitioning from Residential to Family Care for Children
Authors: Wilke Nicole Gilbertson , Howard Amanda Hiles , King David , Carroll Brian
Published: October 2021

Research suggests that children develop best in families. However, millions of children live in residential care centres worldwide. Many residential centres desire to transition their programs from a residential to a family-based model of care, but face barriers surrounding funding and donor support. Little research exists on how organisations address these concerns. The current article investigated the financial impact of transitioning to a family-based model of care, donor engagement practices used in this process, and changes in donor support resulting from the transition. Twenty-six organisations that had fully or partially transitioned their model completed a brief survey. Data revealed an initial increase in cost per child, but long-term the cost of services decreased. Further, findings suggested that involving donors early and using multiple methods and types of communication led to better long-term donor support. Based on these findings, five recommendations were made for organisations planning to transition their care model.
A Patient-Centered Design Thinking Workshop to Improve Patient-Provider Communication in Cardiovascular Medicine
Authors: Cuddihy Meghan J , Servoss Jonathan M , Lee Joyce , Martin Bradley J , Beach Jamie , Ghanbari Hamid , Eagle Kim A , Vemuri Chandu
Published: October 2021

Healthcare providers are expected to deliver care improvement solutions that not only provide high quality patient care, but also improve outcomes, reduce costs, ensure safety, and increase patient satisfaction. Human-centered design methodologies, such as design thinking, allow providers to collaboratively ideate solutions with patients and family members. We describe a pilot workshop designed to teach providers the stages of design thinking while working on improving patient-provider communication. Twenty-four providers (physicians, nurses, technical staff, and administrative staff) from multiple cardiovascular units attended the workshop with five former patients and family members from those units. The workshop educated on and guided teams of providers patients and family members through the stages of design thinking (empathy, define, ideate, prototype, test). Pre- and post-event assessments indicated an increase in knowledge of the design thinking methodology and participants’ ability to apply it to a clinical problem. We also present recommendations for designing a successful design thinking workshop.
Signatures of GVHD and relapse after posttransplant cyclophosphamide revealed by immune profiling and machine learning
Authors: McCurdy Shannon R. , Radojcic Vedran , Tsai Hua-Ling , Vulic Ante , Thompson Elizabeth , Ivcevic Sanja , Kanakry Christopher G. , Powell Jonathan D. , Lohman Brian , Adom Djamilatou , Paczesny Sophie , Cooke Kenneth R. , Jones Richard J. , Varadhan Ravi , Symons Heather J. , Luznik Leo
Published: October 2021

The key immunologic signatures associated with clinical outcomes after posttransplant cyclophosphamide (PTCy)-based HLA-haploidentical (haplo) and HLA-matched bone marrow transplantation (BMT) are largely unknown. To address this gap in knowledge, we used machine learning to decipher clinically relevant signatures from immunophenotypic, proteomic, and clinical data and then examined transcriptome changes in the lymphocyte subsets that predicted major posttransplant outcomes. Kinetics of immune subset reconstitution after day 28 were similar for 70 patients undergoing haplo and 75 patients undergoing HLA-matched BMT. Machine learning based on 35 candidate factors (10 clinical, 18 cellular, and 7 proteomic) revealed that combined elevations in effector CD4+ conventional T cells (Tconv) and CXCL9 at day 28 predicted acute graft-versus-host disease (aGVHD). Furthermore, higher NK cell counts predicted improved overall survival (OS) due to a reduction in both nonrelapse mortality and relapse. Transcriptional and flow-cytometric analyses of recovering lymphocytes in patients with aGVHD identified preserved hallmarks of functional CD4+ regulatory T cells (Tregs) while highlighting a Tconv-driven inflammatory and metabolic axis distinct from that seen with conventional GVHD prophylaxis. Patients developing early relapse displayed a loss of inflammatory gene signatures in NK cells and a transcriptional exhaustion phenotype in CD8+ T cells. Using a multimodality approach, we highlight the utility of systems biology in BMT biomarker discovery and offer a novel understanding of how PTCy influences alloimmune responses. Our work charts future directions for novel therapeutic interventions after these increasingly used GVHD prophylaxis platforms. Specimens collected on NCT0079656226 and NCT0080927627 https://clinicaltrials.gov/.
Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitro
Authors: Liu Zhi-Jian , Deschmann Emoke , Ramsey Haley E. , Feldman Henry A. , Psaila Bethan , Cooper Nichola , Vlachodimitropoulou Evangelia , Porter John , Bussel James , Georgieff Michael , Sola-Visner Martha
Published: October 2021

Eltrombopag (ELT) is a thrombopoietic agent approved for immune thrombocytopenia and also a potent iron chelator. Here we found that ELT exhibited dose-dependent opposing effects on in vitro megakaryopoiesis: low concentrations (≤6 µM, ELT6) stimulated megakaryopoiesis, but high concentrations (30 µM, ELT30) suppressed megakaryocyte (MK) differentiation and proliferation. The suppressive effects of ELT30 were reproduced by other iron chelators, supporting iron chelation as a likely mechanism. During MK differentiation, committed MK progenitors (CD34+/CD41+ and CD34−/CD41+ cells) were significantly more sensitive than undifferentiated progenitors (CD34+/CD41− cells) to the suppressive effects of ELT30, which resulted from both decreased proliferation and increased apoptosis. The antiproliferative effects of ELT30 were reversed by increased iron in the culture, as were the proapoptotic effects when exposure to ELT30 was short. Because committed MK progenitors exhibited the highest proliferative rate and the highest sensitivity to iron chelation, we tested whether their iron status influenced their response to ELT during rapid cell expansion. In these studies, iron deficiency reduced the proliferation of CD41+ cells in response to all ELT concentrations. Severe iron deficiency also reduced the number of MKs generated in response to high thrombopoietin concentrations by ∼50%, compared with iron-replete cultures. Our findings support the hypothesis that although iron deficiency can stimulate certain cells and steps in megakaryopoiesis, it can also limit the proliferation of committed MK progenitors, with severity of iron deficiency and degree of thrombopoietic stimulation influencing the ultimate output. Further studies are needed to clarify how megakaryopoiesis, iron deficiency, and ELT stimulation are clinically interrelated.
A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease
Authors: Lazaryan Aleksandr , Lee Stephanie , Arora Mukta , Kim Jongphil , Betts Brian Christopher , Khimani Farhad , Nishihori Taiga , Bejanyan Nelli , Liu Hien , Kharfan-Dabaja Mohamed A. , Locke Frederick L. , Gonzalez Rebecca , Jain Michael D. , Davila Marco L. , Perez Lia Elena , Mishra Asmita , Perez Perez Ariel , Balke Karlie , Ayala Ernesto , Ochoa Leonel , Castaneda Puglianini Omar , Faramand Rawan , Alsina Melissa , Elmariah Hany , Nieder Michael L. , Fernandez Hugo , Anasetti Claudio , Pidala Joseph A.
Published: October 2021

Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD.  This trial was registered at www.clinicaltrials.gov as #NCT01680965.
Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature
Authors: Brignardello-Petersen Romina , El Alayli Abdallah , Husainat Nedaa , Kalot Mohamad , Shahid Shaneela , Aljabirii Yazan , Britt Alec , Alturkmani Hani , El-Khechen Hussein , Motaghi Shahrzad , Roller John , Dimassi Ahmad , Abughanimeh Omar , Madoukh Bader , Arapshian Alice , Grow Jean M. , Kouides Peter , Laffan Michael , Leebeek Frank W. G. , O’Brien Sarah H. , Tosetto Alberto , James Paula D. , Connell Nathan T. , Flood Veronica , Mustafa Reem A.
Published: October 2021

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of >0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures.
A role for club cells in smoking-associated lung adenocarcinoma
Authors: Behrend Sabine J. , Giotopoulou Georgia A. , Spella Magda , Stathopoulos Georgios T.
Published: October 2021

The cellular origin of lung adenocarcinoma remains a focus of intense research efforts. The marked cellular heterogeneity and plasticity of the lungs, as well as the vast variety of molecular subtypes of lung adenocarcinomas perplex the field and account for the extensive variability of experimental results. While most experts would agree on the cellular origins of other types of thoracic tumours, great controversy exists on the tumour-initiating cells of lung adenocarcinoma, since this histologic subtype of lung cancer arises in the distal pulmonary regions where airways and alveoli converge, occurs in smokers as well as nonsmokers, is likely caused by various environmental agents, and is marked by vast molecular and pathologic heterogeneity. Alveolar type II, club, and their variant cells have all been implicated in lung adenocarcinoma progeny and the lineage hierarchies in the distal lung remain disputed. Here we review the relevant literature in this rapidly expanding field, including results from mouse models and human studies. In addition, we present a case for club cells as cells of origin of lung adenocarcinomas that arise in smokers.
COVID-19 pneumonia: pathophysiology and management
Authors: Gattinoni Luciano , Gattarello Simone , Steinberg Irene , Busana Mattia , Palermo Paola , Lazzari Stefano , Romitti Federica , Quintel Michael , Meissner Konrad , Marini John J. , Chiumello Davide , Camporota Luigi
Published: October 2021

Coronavirus disease 2019 (COVID-19) pneumonia is an evolving disease. We will focus on the development of its pathophysiologic characteristics over time, and how these time-related changes determine modifications in treatment. In the emergency department: the peculiar characteristic is the coexistence, in a significant fraction of patients, of severe hypoxaemia, near-normal lung computed tomography imaging, lung gas volume and respiratory mechanics. Despite high respiratory drive, dyspnoea and respiratory rate are often normal. The underlying mechanism is primarily altered lung perfusion. The anatomical prerequisites for PEEP (positive end-expiratory pressure) to work (lung oedema, atelectasis, and therefore recruitability) are lacking. In the high-dependency unit: the disease starts to worsen either because of its natural evolution or additional patient self-inflicted lung injury (P-SILI). Oedema and atelectasis may develop, increasing recruitability. Noninvasive supports are indicated if they result in a reversal of hypoxaemia and a decreased inspiratory effort. Otherwise, mechanical ventilation should be considered to avert P-SILI. In the intensive care unit: the primary characteristic of the advance of unresolved COVID-19 disease is a progressive shift from oedema or atelectasis to less reversible structural lung alterations to lung fibrosis. These later characteristics are associated with notable impairment of respiratory mechanics, increased arterial carbon dioxide tension (PaCO2), decreased recruitability and lack of response to PEEP and prone positioning.
Comparative studies on the mechanical properties and microstructures of outerwood and corewood in Pinus radiata D. Don
Authors: Li Ming-yue , Ren Hai-qing , Wang Yu-rong , Gong Ying-chun , Zhou Yong-dong
Published: October 2021

Twenty-year-old Pinus radiata trees imported from New Zealand were investigated, and a comparison was made between the outerwood (rings 16–20) and corewood (rings 4–6) in terms of mechanical properties, anatomical characteristics, microfibril angle (MFA), relative crystallinity, crystallite size and lignin content to determine the relationship between their mechanical properties and microstructures. The results demonstrated that the mechanical properties of the Pinus radiata outerwood were significantly better than those of the corewood. The outerwood had a modulus of rupture (MOR) of 106 MPa, a modulus of elasticity (MOE) of 11.4 GPa, and compressive strength parallel to the grain of 38.7 MPa, and the MOR, MOE and compressive strength parallel to the grain of the corewood were 78.9 MPa, 7.12 GPa and 29.3 MPa, respectively. The observed microstructures of the Pinus radiata outerwood and corewood were different, mainly due to differences in cell wall thickness, MFA, and relative crystallinity. The double wall thickness of the tracheid cells of the corewood and outerwood were 3.65 and 5.02 µm, respectively. The MFA data indicated that the average MFA of the outerwood was 14.0°, which was smaller than that of the corewood (22.3°). With X-ray diffraction, the relative crystallinity of the corewood was determined to be 35.7%, while that of the outerwood was 40.2%. However, the crystallite size of the outerwood cell wall shows no obvious difference from that of the corewood. Imaging FTIR spectroscopy showed a slightly higher relative content of lignin in the cell wall of the outerwood. The correlation between the microstructures and mechanical properties showed that the corewood with a thin cell wall, large MFA and low relative crystallinity had poor mechanical properties, while the outerwood with a thicker tracheid, smaller MFA and higher relative crystallinity had better mechanical properties. This means that the MFA, relative crystallinity and cell wall thickness synergically affect the mechanical properties of Pinus radiata in different radial locations.
Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials
Authors: Crisafulli Salvatore , Luxi Nicoletta , Coppini Raffaele , Capuano Annalisa , Scavone Cristina , Zinzi Alessia , Vecchi Simona , Onder Graziano , Sultana Janet , Trifirò Gianluca
Published: October 2021

Background

Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs.

Methods

MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool.

Results

Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk.

Conclusions

This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.
A prospective cohort study providing insights for markers of adverse pregnancy outcome in older mothers
Authors: Lean Samantha C. , Jones Rebecca L. , Roberts Stephen A. , Heazell Alexander E. P.
Published: October 2021

Background

Advanced maternal age (≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of older mothers who are at greatest risk. This study aimed to investigate changes in oxidative stress and inflammation in older women and identify clinical and biochemical predictors of adverse pregnancy outcome in older women.

Methods

The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 528 mothers. Participants were divided into three age groups for comparison 20–30 years (n = 154), 35–39 years (n = 222) and ≥ 40 years (n = 152). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks’ gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age (< 10th centile), FGR (<5th centile), stillbirth, NICU admission, preterm birth < 37 weeks’ gestation or Apgar score < 7 at 5 min. Biomarkers of inflammation, oxidative stress and placental dysfunction were quantified in maternal serum. Univariate and multivariable logistic regression was used to identify associations with adverse fetal outcome.

Results

Maternal smoking was associated with adverse outcome irrespective of maternal age (Adjusted Odds Ratio (AOR) 4.22, 95% Confidence Interval (95%CI) 1.83, 9.75), whereas multiparity reduced the odds (AOR 0.54, 95% CI 0.33, 0.89). In uncomplicated pregnancies in older women, lower circulating anti-inflammatory IL-10, IL-RA and increased antioxidant capacity (TAC) were seen. In older mothers with adverse outcome, TAC and oxidative stress markers were increased and levels of maternal circulating placental hormones (hPL, PlGF and sFlt-1) were reduced (p < 0.05). However, these biomarkers only had modest predictive accuracy, with the largest area under the receiver operator characteristic (AUROC) of 0.74 for placental growth factor followed by TAC (AUROC = 0.69).

Conclusions

This study identified alterations in circulating inflammatory and oxidative stress markers in older women with adverse outcome providing preliminary evidence of mechanistic links. Further, larger studies are required to determine if these markers can be developed into a predictive model of an individual older woman’s risk of adverse pregnancy outcome, enabling a reduction in stillbirth rates whilst minimising unnecessary intervention.
Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center’s experience
Authors: Jeong Jiyoon , Lee Byong Sop , Cha Teahyen , Jung Euiseok , Kim Ellen Ai-Rhan , Kim Ki-Soo , Kim Dae Yeon , Namgoong Jung-Man , Kim Seong Chul , Lee Mi-Young , Won Hye-Sung
Published: October 2021

Background

Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement.

Methods

We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors.

Results

A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50.

Conclusions

The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.
Interventricular septal curvature as an additional echocardiographic parameter for evaluating chronic thromboembolic pulmonary hypertension: a single-center retrospective study
Authors: Matsumura Akane , Shigeta Ayako , Kasai Hajime , Yokota Hajime , Terada Jiro , Yamamoto Keiko , Sugiura Toshihiko , Matsumura Takuma , Sakao Seiichiro , Tanabe Nobuhiro , Tatsumi Koichiro
Published: October 2021

Background

Noninvasive estimation of the actual systolic pulmonary artery pressure measured via right-sided heart catheterization (sPAPRHC) is vital for the management of pulmonary hypertension, including chronic thromboembolic pulmonary hypertension (CTEPH). Evaluation related to the interventricular septum (IVS) is generally performed with only visual assessment and has been rarely assessed quantitatively in the field of echocardiography. Thus, this study aimed to investigate the utility of echocardiographic IVS curvature to estimate sPAPRHC in patients with CTEPH.

Methods

Medical records of 72 patients with CTEPH were studied retrospectively. We estimated sPAPRHC using echocardiographic IVS curvature (esPAPcurv) and left ventricular eccentricity index (esPAPLVEI), and compared their ability to predict sPAPRHC with estimated sPAPRHC using tricuspid regurgitant pressure gradient (esPAPTRPG).

Results

IVS curvature and LVEI were significantly correlated with sPAPRHC (r = − 0.52 and r = 0.49, respectively). Moreover, the IVS curvature was effective in estimating the sPAPRHC of patients with trivial tricuspid regurgitation (r = − 0.56) and in determining patients with sPAPRHC ≥ 70 mmHg with higher sensitivity (77.0%) compared to those with esPAPTRPG and esPAPLVEI.

Conclusion

Our results indicate that the echocardiographic IVS curvature could be a useful additional tool for estimating sPAPRHC in CTEPH patients for whom accurate estimation of sPAPRHC using tricuspid regurgitant pressure gradient is challenging.
One-year follow-up after treatment of proximal and/or middle one-third humeral shaft fractures with a helical plate: healing rates, complications and functional outcome measures
Authors: Maes V. , Putzeys G.
Published: October 2021

Background

Conventional plate osteosynthesis is a valuable treatment option in displaced proximal and/or middle one-third humeral shaft fractures. Nonetheless, this procedure can be complicated by a radial nerve palsy. To date, many surgical techniques have been developed in an attempt to minimize this high-impact complication. A helical plate has the potential to avoid an iatrogenic radial nerve palsy due to its design. This article aims to evaluate safety and functional outcomes of patients treated with a helical plate compared to conventional plate osteosynthesis. In particular healing rates, complications and functional outcome measures.

Methods

We retrospectively included all patients with displaced proximal and/or middle one-third humeral shaft fractures who were treated with a helical plate from October 2016 until August 2018 at a single level-1 trauma center (AZ Groeninge, Kortrijk, Belgium). A self-molded long PHILOS plate (DePuy Synthes®) or a pre-contoured A.L.P.S proximal humeral plating system (Zimmer Biomet®) were used. Patient baseline characteristics and standard radiographs were obtained pre- and postoperatively. We retrospectively searched for complications. Patients were reassessed using the Disabilities of the Arm, Shoulder and Hand (DASH), Constant Murley (CMS) and EQ-5D-5L scores with a minimal follow-up of 1 year.

Results

The humeral shaft fractures of all sixteen patients consolidated within 3 months and no iatrogenic radial nerve palsies were observed. One plate had to be removed after 1 year due to a late deep infection. With a minimum follow up of 1 year, the mean DASH score was 22 ± 19 and the mean normalized CMS was 80 ± 19.

Conclusion

Operative treatment of proximal and/or middle one-third humeral shaft fractures with a helical plate is a safe procedure with good to excellent shoulder function at one-year follow-up. Contrary to conventional plate osteosynthesis, a helical plate has the potential to completely avoid a radial nerve palsy, while maintaining similar healing rates and functional outcomes.

Trial registration

Retrospective cohort study. B396201939564. Registered on 10 MAY 2019.
Efficacy and safety of dual intravenous artesunate plus quinine compared to intravenous artesunate for cerebral malaria in a triple blinded parallel multisite randomized controlled trial in Nigerian children: DUAL PAQ TRIAL Protocol
Authors: Alao Michael Abel , Orimadegun Adebola Emmanuel , Ibrahim Olayinka Rasheed , Oyenuga Abayomi O. , Asinobi Adanze Onyenonachi , Gbadero Daniel Adedosu , Okoye Ifeoma Joy , Nna Emmanuel Okechukwu
Published: October 2021

Background

Evidence exists as to the criticality of the first 24 h in the management of cerebral malaria. The morbidity and the mortality rate (35%) with the current intravenous monotherapy for the initial treatment of cerebral malaria are unacceptably high. Combination therapy and a shorter course of effective medication have been shown to improve outcomes in human participants in the treatment of other diseases. This study outlines a protocol to conduct a triple blinded parallel randomized controlled trial on cerebral malaria using dual intravenous medications compared to the current standard of monotherapy.

Methods

This is a parallel multi-site randomized controlled superiority triple blinded trial consisting of intravenous artesunate plus quinine and a control arm of intravenous artesunate only. Eligible and assenting children aged 6 months to 17 years will be recruited from 4 tertiary hospitals by random selection from the list of tertiary hospitals in Nigeria. Participants will be randomized and assigned in parallel into two arms using random numbers generated from GraphPad Prism (version 9) by a clinical pharmacologist who has no link with the investigators, the patients, or the statistician. The primary measurable outcome is survival at 12, 24, and 48 h post-randomization. A composite secondary outcome consists of the number of children that regained consciousness, parasitaemia and defervescence at 12 and 24 h post-randomization and haematological and inflammatory markers at 24 and 48 h post-randomization. Adverse events both solicited and unsolicited are recorded all through the study post-randomization. The study is approved by the State Research Ethics Review Committee. Data analysis will be performed in GraphPad Prism version 9.

Discussion

The outcome of this analysis will give insight into the efficacy and safety of dual intravenous antimalaria in the treatment of cerebral malaria among Nigerian children compared with the standard of care. The safety profile of this intervention will also be highlighted. This may help inform physicians on the optimal treatment for cerebral malaria to improve outcomes and reduce recrudescence and treatment failure.

Trial registration

Pan Africa Clinical Trial Registry PACTR202102893629864. 23/02/2021.
Copeptin: a potential blood biomarker for acute ischemic stroke
Authors: Oraby Mohammed I. , Soliman Rasha H. , Abd Elkareem Rehab M. , Mohammed Amna I.
Published: October 2021

Background

Copeptin is a new blood biomarker for acute ischemic stroke which emerged to assist clinicians with decision-making. Serum copeptin can accurately reflect vasopressin concentration, which plays a role in aggravation of inflammatory responses, ions and neurotransmitters dysfunctions. The objective of this work was to investigate the relation between copeptin level as a blood biomarker and the short-term prognosis of acute ischemic stroke after 3 months. The current study included 45 patients with first ever acute ischemic stroke and 45 healthy volunteers as a control. Clinical evaluation, CT and MRI of the brain, NIHSS on admission, and mRS after 3 months were done for the patients, and all the patients and control were subjected to assessment of serum level of copeptin by ELISA technique.

Results

Copeptin level was significantly higher in patients with acute ischemic stroke compared to healthy control subjects (p-value = 0.001). Also, copeptin level was significantly higher in patients with severe stroke (NIHSS > 16) than in those with mild-to-moderate stroke (NIHSS 0–15) at presentation and in patients with unfavorable outcome (mRS 3–6) when compared to patients with favorable outcome (mRS 0–2) (p-value = 0.003 and 0.001, respectively).

Copeptin level was significantly lower in patients who received thrombolytic therapy with rTPA (p-value = 0.049).

Conclusion

Copeptin has an interesting potential as a new prognostic biomarker for patients with acute ischemic stroke as its level was significantly higher in patients with severe stroke and in patients with unfavorable outcome.