bluuebunny/crossref_metadata_2025 huggingface dataset:
The systematic use of evidence‐based methodologies and technologies enhances shared decision‐making in the 2018 International Consensus Conference on Patient Blood Management
Authors: Van Remoortel Hans , Aranko Kari , Mueller Markus M. , De Buck Emmy , Devine Dana , Folléa Gilles , Meybohm Patrick , Tiberghien Pierre , Wood Erica M. , Vandekerckhove Philippe , Seifried Erhard
Published: November 2019

Background and objectives

Patient Blood Management (PBM) aims to optimize the care of patients who might need a blood transfusion. The International Consensus Conference on PBM (ICC‐PBM) aimed to develop evidence‐based recommendations on three topics: preoperative anaemia, red blood cell transfusion thresholds and implementation of PBM programmes. This paper reports how evidence‐based methodologies and technologies were used to enhance shared decision‐making in formulating recommendations during the ICC‐PBM.

Materials & Methods

Systematic reviews on 17 PICO (Population, Intervention, Comparison, Outcomes) questions were conducted by a Scientific Committee (22 international topic experts and one methodologist) according to GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methodology. Evidence‐based recommendations were formulated using Consensus Development Conference methodology.

Results

We screened 17 607 references and included 145 studies. The overall certainty in the evidence of effect estimates was generally low or very low. During the ICC, plenary sessions (100–200 stakeholders from a range of clinical disciplines and community representatives) were followed by closed sessions where multidisciplinary decision‐making panels (>50 experts and patient organizations) formulated recommendations. Two chairs (content‐expert and methodologist) moderated each session and two rapporteurs documented the discussions. The Evidence‐to‐Decision template (GRADEpro software) was used as the central basis in the process of formulating recommendations.

Conclusion

This ICC‐PBM resulted in 10 clinical and 12 research recommendations supported by an international stakeholder group of experts in blood transfusion. Systematic, rigorous and transparent evidence‐based methodology in a formal consensus format should be the new standard to evaluate (cost‐) effectiveness of medical treatments, such as blood transfusion.
Blood donor‐derived buffy coat to produce platelets in vitro
Authors: Marini Irene , Rigoni Flavianna , Zlamal Jan , Pelzl Lisann , Althaus Karina , Nowak‐Harnau Stefanie , Rondina Matthew T. , Bakchoul Tamam
Published: November 2019

Background and objectives

Platelet transfusion is a standard medical therapy used to treat several bleeding disorders. However, a critical drawback is the dependency on donor‐derived platelets, which leads to concerns like insufficient availability and immunological complications. In vitro platelet production from hematopoietic progenitor cells (CD34) may represent a reasonable solution.

Materials and methods

CD34+ cells were isolated from either buffy coat or peripheral blood and compared in terms of platelet production in vitro. The number and the quality of magnetically isolated CD34+ cells and their capability to differentiate into mature megakaryocytes were investigated using flow cytometry. Additionally, the functionality of megakaryocytes in term of in vitro platelet production was tested.

Results

Similar purity and quantity of CD34+ cells was found after their isolation from both cell sources. In contrast, after 6 days of culture, enhanced number of CD34+ cells isolated from buffy coat compared with peripheral blood was observed (5·3 x 106 vs. 3·0 x 106, respectively). Interestingly, despite a comparable nuclear maturation phenotype, the yield of platelets released from buffy coat‐derived megakaryocytes was significantly higher than from peripheral blood cells (platelet yield pro MK: 7·2 vs. 2·7, respectively). Importantly, platelets produced from buffy coat‐derived cells could be activated by agonists.

Conclusion

Haematopoietic progenitor cells isolated from buffy coat have increased yield of platelets released from mature megakaryocytes and enhanced in vitro functionality, compared with peripheral blood‐derived cells. Our study, suggests that buffy coat, obtained during blood donation processing, might be a promising source of megakaryocytes for in vitro platelet production.
Servo System Identification Based on Curve Fitting to Phase-Plane Trajectory
Authors: Shi Xiaoli , Han Yong , Wu Jianhua , Xiong Zhenhua
Published: November 2019

Many methods have been proposed to identify servo system parameters. However, problems still remain in widely applied offline identification methods, for example, the describing-function-based relay feedback method has the ineradicable approximation error, and acceleration information is indispensable for the least-squares method. In order to identify systems accurately and efficiently with less servo system information, this article proposes a novel method to identify servo system parameters through curve fitting to the phase-plane trajectory under the help of one optimization method. Specifically, the phase-plane trajectory expression of the single-degree-of-freedom system is derived; the process on how to convert the servo system identification problem to a curve-fitting optimization problem is described in detail; and the guidelines of the initial parameter setting are introduced. Simulations and experiments are carried out to verify the efficiency of the proposed method. Finally, a feed-forward control based on the identified parameters is designed to further validate the identification accuracy.
Enhanced Performance of Ultrasonic Welding of Short Carbon Fiber Polymer Composites Through Control of Morphological Parameters
Authors: Lee Tae Hwa , Fan Hua-Tzu , Li Yang , Shriver Daniel , Arinez Jorge , Xiao Guoxian , Banu Mihaela
Published: November 2019

Ultrasonic welding (USW) is one of the joining technologies that can be applied to short carbon fiber thermoplastic composites. In this study, the USW of Nylon 6 reinforced by short carbon fibers created using injection molding is used to investigate the USW process without energy directors. In addition to process parameters and performance parameters, a new category of parameters is introduced to characterize the behavior of base materials to control USW without energy directors. These parameters, named morphological parameters, are the degree of crystallinity (DoC) and the ratio of the crystalline phases of Nylon 6 (α/γ ratio). One method of controlling the morphological parameters is annealing. A design of experiments is carried out using 5 replicates and 7 annealing temperatures above the glass transition temperature (Tg) and below the melting temperature (Tm) of Nylon 6 to investigate the influence of annealing on the morphological parameters. The DoC and α/γ ratio are measured for each replicate by utilizing differential scanning calorimetry and X-ray diffraction. The results show that the DoC becomes uniform and the α/γ ratio increases after annealing. Consequently, the variation in weld strength decreases and the average weld strength increases by controlling the morphological parameters through annealing.
Experimental and Numerical Investigation on Ductile Fracture of Steel Pipelines
Authors: Mohajer Rahbari Nima , Xia Mengying , Liu Xiaoben , Roger Cheng J. J. , Adeeb Samer
Published: November 2019

Rupture of steel pipelines leads to the loss-of-containment that may be accompanied with loss of life or damage to property and environment. Therefore, the understanding of the fracture characteristics of steel grades used in the pipelines is essential for a safe and reliable design. In this study, a set of small-scale fracture tests was designed and conducted in order to characterize the fracture of X65 steel grade. The experimental results show that not only is the fracture strain dependent on the triaxial stress condition but also the three-dimensional nature of the stress field considerably affects the ductile fracture toughness. Moreover, parallel finite element (FE) simulation of experiments were conducted and a hybrid experimental–numerical approach was used to calibrate the Mohr–Coulomb fracture criterion and obtain the equivalent plastic strain to fracture of X65 steel as a three-dimensional function of stress triaxiality and Lode angle. An engineering application friendly ductile fracture model is proposed for X65 steel pipelines.
Development of Experimental Technology for Simulated Fuel-Assembly Heating to Address Core-Material-Relocation Behavior During Severe Accident
Authors: Abe Yuta , Yamashita Takuya , Sato Ikken , Nakagiri Toshio , Ishimi Akihiro
Published: November 2019

The authors are developing an experimental technology for simulating severe accident (SA) conditions using simulant fuel material (ZrO2) that would contribute, not only to Fukushima Daiichi (1 F) decommissioning, but also to enhance the safety of worldwide existing and future nuclear power plants through clarification of accident progression behavior. Nontransfer (NTR) type plasma, which has been in practical use with a large torch capacity as high as 2 MW, has the potential to heat subject materials to very high-temperatures without selecting the target to be heated. When simulating 1 F with SA code (Severe Core Damage Analysis Package (SCDAP), Methods for Estimation of Leakages and Consequences of Releases (MELCOR) and Modular Accident Analysis Program (MAAP)), the target of this core-material-melting and relocation (CMMR) experiment was to confirm that NTR plasma has a sufficient heating performance realizing large temperature gradients (>2000 K/m) expected under 1 F conditions. The authors selected NTR-type plasma-heating technology that has the advantage of continuous heating in addition to its high-temperature level. A prototype large-scale experiment (1 m × 0.3 m dia.), called CMMR-0, was conducted in 2016, in which a large temperature gradient was realized and basic characteristics of a heated test assembly were studied. However, the maximum temperature was limited in this test by the instability of the plasma torch under low-oxygen concentrations. It was clarified through this test that an improvement in plasma-heating technology was necessary to heat the large-scale test assembly. The CMMR-1/-2 experiments were carried out in 2017 with a test assembly similar to CMMR-0, applying the improved technology (higher heating power and controlled oxygen concentration). In these two tests, heating history was different, resulting in similar physical responses with more pronounced material melting and relocation in the CMMR-2 experiment. The CMMR-2 experiment was selected from the perspective of establishing an experimental technology. The CMMR-2 experiment adopted a 30-min heating period, wherein the power was increased to a level where a large temperature gradient was expected at the lower part of the core under actual 1 F accident conditions. Most of the control blade and channel box migrated from the original position. After heating, the simulated fuel assembly was measured by X-ray-computed tomography (CT) technology and by electron probe micro-analyzer (EPMA). CT pictures and elemental mapping demonstrated its excellent performance with rather good precision. Based on these results, an excellent perspective, in terms of applicability of the NTR-type plasma-heating technology to the SA experimental study, was obtained.
Refining algorithmic estimation of relative fundamental frequency: Accounting for sample characteristics and fundamental frequency estimation method
Authors: Vojtech Jennifer M. , Segina Roxanne K. , Buckley Daniel P. , Kolin Katharine R. , Tardif Monique C. , Noordzij J. Pieter , Stepp Cara E.
Published: November 2019

Relative fundamental frequency (RFF) is a promising acoustic measure for evaluating voice disorders. Yet, the accuracy of the current RFF algorithm varies across a broad range of vocal signals. The authors investigated how fundamental frequency (fo) estimation and sample characteristics impact the relationship between manual and semi-automated RFF estimates. Acoustic recordings were collected from 227 individuals with and 256 individuals without voice disorders. Common fo estimation techniques were compared to the autocorrelation method currently implemented in the RFF algorithm. Pitch strength-based categories were constructed using a training set (1158 samples), and algorithm thresholds were tuned to each category. RFF was then computed on an independent test set (291 samples) using category-specific thresholds and compared against manual RFF via mean bias error (MBE) and root-mean-square error (RMSE). Auditory-SWIPE′ for fo estimation led to the greatest correspondence with manual RFF and was implemented in concert with category-specific thresholds. Refining fo estimation and accounting for sample characteristics led to increased correspondence with manual RFF [MBE = 0.01 semitones (ST), RMSE = 0.28 ST] compared to the unmodified algorithm (MBE = 0.90 ST, RMSE = 0.34 ST), reducing the MBE and RMSE of semi-automated RFF estimates by 88.4% and 17.3%, respectively.
A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein
Authors: DeVincenzo John , Tait Dereck , Efthimiou John , Mori Julie , Kim Young-In , Thomas Elaine , Wilson Lynn , Harland Rachel , Mathews Neil , Cockerill Stuart , Powell Kenneth , Littler Edward
Published: November 2019

Effective treatments for respiratory syncytial virus (RSV) infection are lacking. Here, we report a human proof-of-concept study for RV521, a small-molecule antiviral inhibitor of the RSV-F protein. In this randomized, double-blind, placebo-controlled trial, healthy adults were challenged with RSV-A Memphis-37b.
Medium-Chain Fatty Acid Synthesis by “
Candidatus
Weimeria bifida” gen. nov., sp. nov., and “
Candidatus
Pseudoramibacter fermentans” sp. nov
Authors: Scarborough Matthew J. , Myers Kevin S. , Donohue Timothy J. , Noguera Daniel R.
Published: November 2019

Chain elongation by medium-chain fatty acid (MCFA)-producing microbiomes offers an opportunity to produce valuable chemicals from organic streams that would otherwise be considered waste. However, the physiology and energetics of chain elongation are only beginning to be studied, and many of these organisms remain uncultured. We analyzed MCFA production by two uncultured organisms that were identified as the main MCFA producers in a microbial community enriched from an anaerobic digester; this characterization, which is based on meta-multi-omic analysis, complements the knowledge that has been acquired from pure-culture studies. The analysis revealed previously unreported features of the metabolism of MCFA-producing organisms.
LANA and hnRNP A1 Regulate the Translation of LANA mRNA through G-Quadruplexes
Authors: Dabral Prerna , Babu Jay , Zareie Andrew , Verma Subhash C.
Published: November 2019

LANA, the most abundantly expressed protein during latency, is a multifunctional protein which is absolutely required for the persistence of KSHV in the host cell. Even though the functions of LANA in aiding pathogenesis of the virus have been extensively studied, the mechanism of how LANA escapes host’s immune surveillance is not fully understood. This study sheds light on the autoregulatory role of LANA to modulate its expression and immune evasion through formation of G-quadruplexes in its mRNA. We used G-quadruplex-stabilizing ligand to define the inhibition in LANA expression and presentation on the cell surface through MHC class I. We defined the autoregulatory role of LANA and identified a cellular RNA helicase, hnRNP A1, regulating the translation of LANA mRNA. This interaction of hnRNP A1 with LANA mRNA could be exploited for controlling KSHV latency.
TREM-1 Protects HIV-1-Infected Macrophages from Apoptosis through Maintenance of Mitochondrial Function
Authors: Campbell Grant R. , To Rachel K. , Spector Stephen A.
Published: November 2019

The major challenge to human immunodeficiency virus (HIV) treatment is the development of strategies that lead to viral eradication. A roadblock to accomplishing this goal is the lack of an approach that would safely eliminate HIV from all resting/latent reservoirs, including macrophages. Macrophages are a key part of the innate immune system and are responsible for recognizing invading microbes and sending appropriate signals to other immune cells. Here, we found that HIV induces the upregulation of the protein TREM1 (triggering receptor expressed on myeloid cells 1), which signals an increase in the expression of antiapoptotic proteins, thus promoting survival of HIV-infected macrophages.
Ecology and Host Identity Outweigh Evolutionary History in Shaping the Bat Microbiome
Authors: Lutz Holly L. , Jackson Elliot W. , Webala Paul W. , Babyesiza Waswa S. , Kerbis Peterhans Julian C. , Demos Terrence C. , Patterson Bruce D. , Gilbert Jack A.
Published: November 2019

This study is the first to provide a comprehensive survey of bacterial symbionts from multiple anatomical sites across a broad taxonomic range of Afrotropical bats, demonstrating significant associations between the bat microbiome and anatomical site, geographic locality, and host identity—but not evolutionary history. This study provides a framework for future systems biology approaches to examine host-symbiont relationships across broad taxonomic scales, emphasizing the need to elucidate the interplay between host ecology and evolutionary history in shaping the microbiome of different anatomical sites.
Elephantiasisnostras verrucosain the setting of lymphoedematardaand neurofibromatosis type 1
Authors: Calvão Joana , Santiago Luís , Brites Maria Manuel , Figueiredo Américo
Published: November 2019

Elephantiasisnostras verrucosa(ENV) comprises an uncommon skin disease characterised by dermal fibrosis with hyperkeratotic, verrucous and papillomatous lesions that usually occur after chronic lymphoedema. We describe the case of a 56-year-old-man with neurofibromatosis type 1, no known surgical history, no chronic medication and no travel history, presenting with worsening non-pitting oedema and impressive foul-smelling mossy plaques and cobblestone-like nodules in both legs and feet, especially on the right, compatible with the diagnosis of ENV.
Tumour-bowel fistula as a possible complication of pazopanib therapy in retroperitoneal leiomyosarcoma
Authors: Pereira Rodrigo Otavio Lami , Patel Payal R , Guru Pramod K , Sanghavi Devang K
Published: November 2019

Pazopanib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) that inhibits the vascular endothelial growth factor receptor A pathway and has the potential to cause ischaemic bowel changes, including perforation. Here we report a case of a 51-year-old man with large, metastatic, retroperitoneal leiomyosarcoma that developed a tumour-bowel fistula after 4 weeks of pazopanib therapy. He presented to the emergency department with sepsis and 1-week history of worsening fever, chills, nausea and diarrhoea. Abdominal CT findings of mesenteric and portal vein gas, commonly found in mesenteric ischaemia and VEGFR modulator-induced bowel toxicity, provided evidence for the causal relation. Unfortunately, the case was not amenable to surgery and patient succumbed to the illness.
Rare case of peristomal pemphigus vulgaris in an operated case of carcinoma of the rectum
Authors: Bhange Snehal A , Bhansali Mehul , Shaikh Tanveer , Ajgaonkar Utkarsh
Published: November 2019

Pemphigus vulgaris (PV), in association with malignancy of the rectum, is a very rare presentation. We present here a case of a 58-year-old woman presenting with atypical skin eruptions in the peristomal area, which gradually progressed to her entire body. These lesions were later diagnosed to be PV. She developed these lesions in her postoperative period following an anterior resection with a covering ileostomy for her rectal malignancy. She had received neoadjuvant chemo+radiotherapy for her malignancy.
Lessons learned in the challenging case of evolving compartment syndrome with atypical presentation
Authors: Ng Jessica , Makaram Navnit , Mitchell Sarah
Published: November 2019

We present the rare case of a non-painful compartment syndrome of the forearm in a 35-year old man with a history of intravenous drug abuse, and lessons learned which would have enabled earlier consideration of this limb threatening condition and earlier therapeutic intervention.

On initial assessment in the emergency department, the patient was drowsy, tachycardic and pyrexic. There was no obvious pain outwith expectation, and his forearm was erythematous and swollen. Due to the constellation of symptoms and signs, he was presumed to be septic from a forearm cellulitis and was thus treated for sepsis with intravenous antibiotics under the care of the medical team. As his arm swelling continued, he was then thought to possibly have a vascular issue and was given a therapeutic dose of low molecular weight heparin. He was otherwise pain free throughout and had no evidence of neurological compromise. A subsequent orthopaedic review raised the concern of compartment syndrome, and this, alongside a clinically evolving picture, resulted in a diagnosis of developing compartment syndrome being made. The patient underwent subsequent surgical management with dual incision fasciotomies and definitive wound management with split skin graft under the care of plastic surgery.

This is a rare presentation of a masked developing compartment syndrome. This case highlights the importance of considering atypical presentations of compartment syndrome in high risk patients, and the importance of early specialist orthopaedic referral, particularly in those who do not present with typical features in their history and examination. We summarise the lessons learned in this case which would have enabled earlier identification of this limb-threatening diagnosis and could have improved further definitive outcome.
Attenuated familial adenomatous polyposis (AFAP) in a patient associated with a novel mutation in APC
Authors: Sant Vivek , Reich Elsa , Khanna Lauren , Cao Wenqing , Kornacki Susan , Grucela Alexis
Published: November 2019

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome associated with mutation in the adenomatous polyposis coli (APC) gene, a tumour suppressor located on chromosome 5q21. Attenuated familial adenomatous polyposis (AFAP) is a variant associated with fewer and later onset of colon polyps. AFAP-associated APC mutations have largely been found before codon 157, in exon 9 or after codon 1595. We present the case of a 44-year-old man incidentally found to have numerous gastric polyps during bariatric surgery, with innumerable polyps in the remaining part of the stomach and the entire colon, with rectal sparing, consistent with AFAP phenotype. Genetic testing demonstrated the c.7682dup (p.Ser2562Lysfs*21) variant in exon 15 of APC. This represents a previously undescribed APC mutation. This mutation likely yields end-binding protein 1 and human disc large binding protein inactivation, causing cell cycle microtubule dysregulation and tumour suppressor inactivation. Through loss of these regulatory mechanisms, this mutation is associated with AFAP phenotype. The patient was treated surgically and is doing well.
Cancer-associated retinopathy in ampullary pancreatic cancer
Authors: Ghadiri Nima , Yang Yunfei , Burton Benjamin JL
Published: November 2019

A 64-year-old woman presented with bilateral visual loss with shimmering photopsias as the only clinical manifestation of an occult pancreatic ampullary adenocarcinoma causing duct dilatation. Abnormal electroretinograms led to suspicion of cancer-associated retinopathy (CAR), and CT of the abdomen showed an underlying pancreatic malignancy, detected with subclinical liver function tests following diagnosis of CAR. Biopsy showed a T2N0M0 ampullary adenocarcinoma. The patient was managed with Whipple’s procedure and adjuvant chemotherapy and has made a good recovery with no progression of her retinopathy. To our knowledge, this is one of the first descriptions of CAR in the context of pancreatic malignancy. It is atypical in its asymmetric presentation and favourable patient outcome. CAR is an important diagnosis to make, as ocular manifestations can be the only indication of an occult malignancy, resulting in a swifter diagnosis and potentially life-saving early intervention.
Atypical marantic endocarditis
Authors: Umeojiako Wilfred Ifeanyi , Kasouridis Ioannis , Sargent Robert , Ghani Saqib
Published: November 2019

Marantic endocarditis is a rare non-infectious endocarditis that mostly affects the aortic and mitral valves. It is often an autopsy finding that is most commonly seen in advanced malignancies thought to be due to a hypercoagulable state. When diagnosed antemortem, it typically presents with signs and symptoms of embolisation. We report a case of a 44-year-old Caucasian man with marantic endocarditis secondary to metastatic small cell lung cancer. Our patient presented with a short history of lower back pain with no signs/symptoms of embolisation, and a pansystolic murmur on initial physical examination. Serial blood cultures were negative and transthoracic echocardiography revealed vegetation on the posterior leaflet of the mitral valve. Further imaging in the form of MRI spine and CT thorax/abdomen/pelvis showed pulmonary lesions with liver and bony metastasis. Subsequent image-guided biopsy confirmed metastatic small cell lung cancer of T1N2M1c grade, which was treated with palliative chemotherapy and radiotherapy.
Bilateral sixth nerve palsies from carotid cavernous fistulas with transient worsening following transvenous embolisation
Authors: Kalaichandran Sivaruben , Micieli Jonathan A
Published: November 2019

A 59-year-old man presented with a 2-week history of binocular horizontal diplopia worse when looking to the left. He was diagnosed with a left sixth nerve palsy (6 NP) and had new bilateral findings at a 2-week follow-up with new dilated episcleral blood vessels. Bilateral carotid-cavernous fistulas (CCFs) were suspected and confirmed with CT angiography and catheter angiography. He underwent successful coil and Onyx embolisation of the left cavernous sinus and immediately noticed worsening of the double vision when looking left due to a worse left 6 NP. Three weeks later, he underwent similar treatment of the right CCF and immediately noticed worsening of the double vision when looking to the right and was found to have a worse right 6 NP. His double vision resolved 6 months later. CCFs are rare causes of bilateral 6 NPs and although there is a good prognosis, symptoms may worsen after treatment.
Persistently poor vision in dim illumination after implantation of XtraFocus small-aperture IOL (Morcher)
Authors: Agarwal Prateek , Navon Samuel Edward , Subudhi Praveen , Mithal Neha
Published: November 2019

A 21-year-old patient presents to us with complaints of blurred vision and photophobia in the left eye, with an uncorrected visual acuity of 20/100 improving to 20/30 with pinhole and diagnostic rigid gas permeable lens trial. He had a history of trauma with subsequent cataract extraction, with residual irregular astigmatism and traumatic mydriasis. XtraFocus Pinhole intraocular lens (Morcher) was implanted in the left eye. One week postoperatively, the left eye uncorrected visual acuity improved to 20/30, uncorrected intermediate visual acuity improved to 20/40, and uncorrected near visual acuity improved to J4. The glare and photophobia resolved completely. Surprisingly, the patient complained of severely poor vision in dim illumination. His vision was limited to bare perception of objects and hand movements close to the face. He started facing difficulties in major activities such as driving at night and in dark ambient surroundings such as movie theatres, which persisted to the extent of necessitating explantation of the implant.
Levetiracetam is a useful alternative to phenytoin for epileptic seizures in children
Authors: Cook Rob , Davidson Peter , Martin Rosie
Published: November 2019

The study

Lyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet 2019;393:2125-34.

This trial was funded by the NIHR Health Technology Assessment Programme (project number 12/127/134).

To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000790/levetiracetam-vs-phenytoin-in-stopping-childrens-prolonged-epileptic-seizures
Development of a longlist of healthcare quality indicators for physical activity of patients during hospital stay: a modified RAND Delphi study
Authors: Koenders Niek , van den Heuvel Stein , Bloemen Shanna , van der Wees Philip J , Hoogeboom Thomas J
Published: November 2019

Objective

To develop a longlist of healthcare quality indicators for the care of hospitalised adults of all ages with (or at risk of) low physical activity during the hospital stay.

Design

A modified RAND/UCLA Appropriateness Method Delphi study.

Setting and participants

Participants were physical therapists, nurses and managers working in Dutch university medical centres.

Methods

The current study consisted of three phases. Phase I was a systematic literature search for quality indicators and relevant domains. Phase II was a survey among healthcare professionals to collect additional data. Phase III consisted of three consensus rounds. In round 1, experts rated the relevance of the potential indicators online (Delphi). The second round was a face-to-face expert panel meeting managed by an experienced moderator. Acceptability, feasibility and validity of the quality indicators were discussed by the panel members. In round 3, the panel members rated the relevance of the potential indicators that were still under discussion.

Results

The search retrieved 1556 studies of which 53 studies were assessed full text. Data from 17 studies were included in a first draft longlist of indicators. Eighteen nurses and one physical therapist responded to the survey and added data for a second draft of the longlist. Experts constructed the final longlist of 23 indicators in three consensus rounds. Seven domains were identified: ‘Policy’, ‘Attitude and education’, ‘Equipment and support’, ‘Evaluation’, ‘Information’, ‘Patient-tailored physical activity plan’ and ‘Outcome measure’.

Conclusion and implications

The healthcare quality indicators developed in this study could help to grade, monitor and improve healthcare for hospitalised adults of all ages with (or at risk of) low physical activity during the hospital stay. Future research will focus on the psychometric quality of the indicators and selection of key performance indicators.
Long-term clinical outcomes of keratoplasty using gamma-irradiated corneal lenticules
Authors: Mathews Priya M , Fogla Rajesh , Samayoa Erik , VanCourt Shanna , Akpek Esen K
Published: November 2019

Objective

To report long-term clinical outcomes of gamma-irradiated corneal lenticules in partial and full-thickness keratoplasty.

Methods and Analysis

This multicentre, retrospective case series includes 23 patients who underwent surgery at three centres (India, Guatemala, and USA) between May 2009 and March 2018. The main outcome measures were epithelialization and retention for therapeutic keratoplasty and best spectacle-corrected visual acuity (BSCVA) for optical keratoplasty.

Results

Patients were categorised according to primary aetiology requiring corneal transplantation: non-inflammatory conditions, infectious keratitis and sterile keratolysis. Nine patients with non-inflammatory conditions underwent anterior lamellar keratoplasty (n=7) and Boston type 1 keratoprosthesis (n=2). All nine grafts remained intact and epithelialized during follow-up (median 24 months). In the seven patients who underwent anterior keratoplasty, the graft stayed optically clear during follow-up (median 12 months), with BSCVA between 20/20 and 20/40 in all but one patient who developed cataract. Nine patients with severe infectious keratitis had emergency patch grafting. Six of those grafts epithelialized and remained intact over a median of 30 months, providing tectonic support until optical keratoplasty with fresh tissue could be performed. Three grafts had recurrent infectious keratitis 1–3 months postoperatively, two of which underwent tectonic keratoplasty with fresh tissue which also eventually became infected during follow-up. In five additional patients with sterile keratolysis who underwent lamellar patch graft, two grafts remained intact during follow-up (median 36 months). Two patients had recurrent corneal melt within 1 month, and both had subsequent corneal surgery with fresh tissue which also failed. There were no donor-related complications.

Conclusion

Gamma-irradiated sterile corneal stromal lenticules can be considered as a viable alternative to fresh tissue in various clinical settings.
Leprosy in children: a Cuban experience on leprosy control
Authors: Ruiz-Fuentes Jenny Laura , Rumbaut Castillo Raisa , Hurtado Gascón Laura de la Caridad , Pastrana Fernanda
Published: November 2019

Background

Children are believed to be the most vulnerable group to leprosy. Childhood leprosy reflects disease transmission in the community as well as the efficiency of ongoing disease control programmes. In Cuba, leprosy is not a national health problem; however, new childhood leprosy cases are diagnosed every year.

Objective

We summarise the experience of Cuba on childhood leprosy control over the past two decades.

Results

Between 2000 and 2017, a total of 103 children in Cuba have been diagnosed with leprosy, showing that active transmission of cases remains in 13 of 15 provinces of Cuba. The majority of cases were multibacillary (66%), and 34% were paucibacillary cases. Clinically 60% of children have more than five lesions all over their body. Voluntary reporting was the principal method of case detection. The presence of familial and extrafamilial contact with leprosy cases may be a cause of concern, as it implies continuing transmission of the disease. Only four children had disabilities (one with grade 2 disabilities and three with grade 1 disabilities). A set of national investigations have been developed to intervene in a timely manner. Intervention strategies that combine clinical surveillance and laboratory test could be an option for early detection of childhood leprosy.

Conclusions

Early detection of cases due to effective health education campaigns, regular and complete treatment with MDT, and contact tracing may be important in reducing the burden of leprosy in the community.
Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex
Authors: Kato Kohji , Oka Yasuyoshi , Muramatsu Hideki , Vasilev Filipp F , Otomo Takanobu , Oishi Hisashi , Kawano Yoshihiko , Kidokoro Hiroyuki , Nakazawa Yuka , Ogi Tomoo , Takahashi Yoshiyuki , Saitoh Shinji
Published: November 2019

Background

3C/Ritscher-Schinzel syndrome is characterised by congenital cranio-cerebello-cardiac dysplasia, where CCDC22 and WASHC5 are accepted as the causative genes. In combination with the retromer or retriever complex, these genes play a role in endosomal membrane protein recycling. We aimed to identify the gene abnormality responsible for the pathogenicity in siblings with a 3C/Ritscher-Schinzel-like syndrome, displaying cranio-cerebello-cardiac dysplasia, coloboma, microphthalmia, chondrodysplasia punctata and complicated skeletal malformation.

Methods

Exome sequencing was performed to identify pathogenic variants. Cellular biological analyses and generation of knockout mice were carried out to elucidate the gene function and pathophysiological significance of the identified variants.

Results

We identified compound heterozygous pathogenic variants (c.1097dup; p.Cys366Trpfs*28 and c.2755G>A; p.Ala919Thr) in the VPS35L gene, which encodes a core protein of the retriever complex. The identified missense variant lacked the ability to form the retriever complex, and the frameshift variant induced non-sense-mediated mRNA decay, thereby confirming biallelic loss of function of VPS35L. In addition, VPS35L knockout cells showed decreased autophagic function in nutrient-rich and starvation conditions, as well as following treatment with Torin 1. We also generated Vps35l−/− mice and demonstrated that they were embryonic lethal at an early stage, between E7.5 and E10.5.

Conclusions

Our results suggest that biallelic loss-of-function variants in VPS35L underlies 3C/Ritscher-Schinzel-like syndrome. Furthermore, VPS35L is necessary for autophagic function and essential for early embryonic development. The data presented here provide a new insight into the critical role of the retriever complex in fetal development.
Rotating and non-rotating AdS black holes in $$f(\mathcal{T})$$ gravity non-linear electrodynamics
Authors: Capozziello Salvatore , Nashed Gamal G. L.
Published: November 2019

We derive new exact charged d-dimensional black hole solutions for quadratic teleparallel equivalent gravity, $$f(\mathcal{T})=a_0+a_1\mathcal{T}+a_2\mathcal{T}^2$$f(T)=a0+a1T+a2T2, where $$\mathcal T$$T is the torsion scalar, in the case of non-linear electrodynamics. We give a specific form of electromagnetic function and find out the form of the unknown functions that characterize the vielbeins in presence of the electromagnetic field. It is possible to show that the black holes behave asymptotically as AdS solutions and contain, in addition to the monopole and quadrupole terms, other higher order terms whose source is the non-linear electrodynamics field. We calculate the electromagnetic Maxwell field and show that our d-dimensional black hole solutions coincide with the previous obtained one (Awad et al. in J High Energy Phys 13:1706.01773, 2017). The structure of the solutions show that there is a central singularity that is much mild in comparison with the respective one in general relativity. Finally, the thermodynamical properties of the solutions are investigated by calculating the entropy, the Hawking temperature, the heat capacity, and other physical quantities. The most important result of thermodynamics is that the entropy is not proportional to the area of the black hole. This inanition points out that we must have a constrain on the quadrupole term to get a positive entropy otherwise we get a negative value.
WHAT CAME FIRST, TRANSPORTATION OR URBANIZATION?
Authors: LIU TIE-YING , SU CHI-WEI , QIN MENG , ZHANG XIAO-YAN
Published: November 2019

This paper proposes new perspective on the nexus between transportation and urbanization in China to test the search-matching theory. We find that the linkage between transportation and urbanization has both frequency and time-varying features. We find that transportation improves urbanization in the short term, while urbanization plays the importation role in transportation during the period 1969–1996. This result obviously supports search-matching theory that in the subsample periods, the transportation infrastructure exerts positive effects on urbanization in the short term but not in the long term. In the long term, urbanization will promote the development of transportation, while short-term traffic infrastructure investment can effectively improve the transfer of population to urban regions. It would be beneficial for the government to formulate the scientific traffic planning policy and adjust the transport structure to improve urbanization.
On the discrete Christoffel symbols
Authors: Khatsymovsky V. M.
Published: November 2019

The piecewise flat space–time is equipped with a set of edge lengths and vertex coordinates. This defines a piecewise affine coordinate system and a piecewise affine metric in it, the discrete analogue of the unique torsion-free metric-compatible affine connection or of the Levi-Civita connection (or of the standard expression of the Christoffel symbols in terms of metric) mentioned in the literature, and, substituting this into the affine connection form of the Regge action of our previous work, we get a second-order form of the action. This can be expanded over metric variations from simplex to simplex. For a particular periodic simplicial structure and coordinates of the vertices, the leading order over metric variations is found to coincide with a certain finite difference form of the Hilbert–Einstein action.
Phenomenology of the partially aligned 2HDM with leptonic meson decays
Authors: Carrillo-Monteverde A. , Gómez-Ávila S. , Gómez-Rosas R. , López-Lozano L. , Rosado A.
Published: November 2019

In this paper we present a phenomenological analysis of the Partially Aligned Two Higgs Doublet Model (PA-2HDM) by using leptonic decays of mesons and [Formula: see text]–[Formula: see text] mixing. We focus our attention in a scenario where the leading contribution to FCNC is given by the tree-level interaction with the light pseudoscalar [Formula: see text] ([Formula: see text] GeV). We show how an underlying flavor symmetry controls FCNC in the quark and lepton couplings with the pseudoscalar, without alignment between Yukawa matrices. Upper bounds on the free parameters are calculated in the context of the leptonic decays [Formula: see text] and [Formula: see text] and [Formula: see text] mixing. Also, our assumptions imply that bounds on New Physics contribution in the quark sector coming from [Formula: see text] mixing impose an upper bound on the parameters for the leptonic sector. Finally we give predictions of branching ratios for leptonic decay of mesons with FCNC and LFV.
Fractal characteristics of Heterocapsa Circularisquama and Prorocentrum Dentatum cells growth
Authors: Liu Changan , Zhao Qiuyue , Hu Changquan , Liu Shutang
Published: November 2019

This paper investigates behaviors that a set of initial cell densities of Heterocapsa Circularisquama (HC) and Prorocentrum Dentatum (PD) and a set of environmental factors disturbing the growth of HC and PD cells formed in their growth process, which are actually fractal phenomena. First, the calculation of the fractal dimension of the set of initial cell densities of HC and PD is given in the paper. Second, by controlling the set of initial cell density, HC and PD cells grow according to a given growth target. The approximate or same behaviors of two different sets of initial cell densities of HC and PD are realized by introducing the coupling terms. Finally, the set of environmental factors disturbing the growth of HC and PD cells is constructed by introducing real parameters. Then the result that makes HC and PD cells growing according to a given growth target is reached by a proper mathematical transform to the real parameters. The approximate or same behaviors of the set of environmental factors disturbing the growth of HC and PD cells are realized by introducing the coupling terms.
A compartmental model for antibiotic resistant bacterial infections over networks
Authors: Knopoff Damián A. , Trucco Facundo A.
Published: November 2019

This paper presents a compartmental model for bacterial infections in a population distributed over a network of individuals. Within each node, individuals interact, bacteria can be transmitted and the disease may be spread; moreover, the acquisition of bacterial antibiotic resistance is considered. In addition, nodes are connected through weighted edges, and consequently individuals from different nodes may interact. As a result, the infection may be propagated over the network. We perform an analysis on this propagation as well as numerical simulations in order to illustrate the validity of the model.
Paleogene volcanic rocks in the northern Faroe–Shetland Basin and Møre Marginal High: understanding lava field stratigraphy
Authors: Walker Faye , Schofield Nick , Millett John , Jolley David , Hole Malcolm , Stewart Margaret
Published: November 2019

Onshore exposures of the North Atlantic Igneous Province have been studied in detail for over 200 years, whereas the more extensive offshore volcanic stratigraphy is significantly less well constrained with the exception of a small number of boreholes. Within this study we integrate seismic and well data across the northern Faroe–Shetland Basin and Møre Marginal High to improve understanding of the volcanic stratigraphy and its relationship to rifting in the NE Atlantic. Volcanic seismic facies, including compound and tabular lavas and hyaloclastites (representing subaerial and subaqueous emplacement), are interpreted across the study area, calibrated by the Lagavulin borehole. The volcanic sequence was erupted between
c.
56.1 and 55.2 Ma, when subaerial conditions dominated in the region, but extensive lava deltas developed in a seaway east of the main lava field. Geochemical and thickness variations within the volcanic pile have important implications for the regional rifting history. MORB-like lavas at the base of Lagavulin, which thicken substantially northward, support an early onset of rifting near the Møre Marginal High prior to major thinning associated with continental breakup to the south and north. Following a period of erosion, smaller-degree melting caused the eruption of higher-TiO
2
/Zr lavas, marking the final ‘pre-breakup’ volcanism before emplacement of seaward-dipping reflectors.
Kinematics of the virtual geomagnetic poles during Brunhes–Matuyama times
Authors: Caminha-Maciel George , Ernesto Marcia
Published: November 2019

Twenty magnetostratigraphic profiles from IODP (International Oceanic Drilling Project) sediment cores distributed on the Earth's surface allowed the scatter of virtual geomagnetic poles (VGPs) during Brunhes–Matuyama times to be examined. We identified two groups of recording sites which give different paths for the VGPs during a time interval of about 1.1 myr. Calculations of the VGP velocities and accelerations, as well as the corresponding azimuths, resulted in mean/median values like those observed for recent times. No significant differences were observed during the ‘stable’ and transitional fields. The acceleration azimuths show variations from north–south to east–west depending on the field state: normal/reversed or transitional. Despite the uncertainties in the magnetization of the sediments (overprints and/or low-resolution records), we demonstrate that the use of this database is valid for obtaining kinematic parameters of the geomagnetic field when analysed on a statistical basis.
Pay as Your Service Needs
Authors: Xie Hong , Wu Weijie , Ma Richard T. B. , Lui John C. S.
Published: November 2019

Various differentiated pricing schemes have been proposed for the Internet market. Aiming at replacing the traditional single-class pricing for better welfare, yet, researchers have shown that existing schemes can bring only marginal profit gain for the ISPs. In this article, we point out that a proper form of differentiated pricing for the Internet should not only consider congestion, but more importantly, it should provide
application specific
treatment to data delivery. Formally, we propose an “application-driven pricing” approach, where an ISP offers a number of service classes in terms of a guaranteed quality of service and announces a unit usage price for each class, and content providers are free to choose which class to use depending on the requirement of their applications. Unlike previous studies, we point out that the revenue gain of multi-class pricing under our scheme can be significant. This is because we capture important aspects of application heterogeneity and take the quality of service and price as control knobs. We identify key factors that impact the revenue gain and reveal fundamental understandings on
when
and
why
an application-driven multi-class pricing can
significantly
increase the revenue of ISPs.