bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapted Dialectical Behavior Therapy for Adolescents with a High Risk of Suicide in a Community Clinic: A Pragmatic Randomized Controlled Trial
Authors: Santamarina‐Perez Pilar , Mendez Iria , Singh Manpreet K. , Berk Michele , Picado Marisol , Font Elena , Moreno Elena , Martínez Esteve , Morer Astrid , Borràs Roger , Cosi Alexandra , Romero Soledad
Published: January 2020

Objective

This study is a pragmatic randomized controlled trial, which compares the effectiveness of an adapted form of Dialectical Behavior Therapy for Adolescents (DBT‐A) and treatment as usual plus group sessions (TAU + GS) to reduce suicidal risk for adolescents in a community health mental clinic.

Method

Thirty‐five adolescents from a community outpatient clinic, with repetitive NSSI alone or with SA over the last 12 months and with current high suicide risk as assessed by the Columbia‐Suicide Severity Rating Scale (C‐SSRS), were enrolled. Participants were randomly assigned to undergo either DBT‐A (n = 18) or TAU + GT (n = 17) treatments over a 16‐week period. Primary outcomes were the difference between NSSI and SA recorded during the first 4 weeks and the final 4 weeks of treatment. Secondary outcomes included changes in Children’s Global Assessment Scale (C‐GAS), Suicidal Ideation Questionnaire (SIQ‐JR), and Beck Depression Inventory‐II (BDI‐II).

Results

Dialectical Behavior Therapy for Adolescents was more effective than TAU + GS at reducing NSSI, use of antipsychotics, and improving C‐GAS. No SAs were reported in the two groups at the end of the treatment. Both treatments were equally effective in decreasing SIQ‐JR and BDI‐II scores.

Conclusions

These findings support the feasibility and effectiveness of DBT‐A for adolescents at high risk of suicide in community settings.
Farming from a Process‐Relational Perspective: Making Openings for Change Visible
Authors: Darnhofer Ika
Published: January 2020

The theoretical debates in sociology have highlighted the strengths, but also the limitations of perspectives building on, anthropocentrism, essentialism, or structural determinism. One school of thought that strives to overcome such limitations is relational sociology. The aim of this article is to explore how a process‐relational perspective can offer a new conceptual framework for farm‐level studies in rural sociology. It is an invitation to view the world as a tissue of interactions, of dynamic and often unpredictable processes. By injecting a dose of new materialism and thereby extending agency to nonhumans, the liveliness of nature and technology is also taken into account. Yet, reconceptualising farming in relational terms is not just a theoretical but also a political project: it spurs different imaginations, making other worlds thinkable. This would enable to show ever‐present openings for more socially just and environmentally friendly farming practices.
Using high‐resolution ultrasound imaging to characterize dermal striae in human skin
Authors: Carvalho Cátia Pinto , Costa‐Júnior José Francisco Silva , Ferreira da Silva Flavia Fernandes , D`Agostinho Juliana Geremia , Krüger Marco Antônio von , Pereira Wagner Coelho de Albuquerque
Published: January 2020

Background and Objective

The improvement in the appearance of the skin with dermal striae (DS) is currently eval‐uated by invasive methods, such as biopsy. This study evaluates whether high‐resolution ultrasound (HRUS) could be used to identify skin lesions in vivo caused by DS, using 2D images and measuring the thickness of the dermal layer.

Methods

High‐resolution ultrasound at frequencies of 20 and 30 MHz was used in this study in ten volunteers with DS. The thickness of the skin layers was estimated by tracing five vertical lines from epidermis (EP) to dermis (DE) and DE to hypodermis (H) surface.

Results

The dermal lesions caused by striae appeared in ultrasonic images as poor echo areas. The average normal DE thickness varied from 1.07 to 1.65 mm, while the DE thickness with DS varied between 0.35 and 1.33 mm. A statistically significant reduction in the DE thickness was found (P‐value < .05) in the presence of DS. The mean values of the EP thickness without and with DS were 0.12 ± 0.03 mm and 0.11 ± 0.02 mm, respec‐tively. A total of 90.00% of the EP‐related groups did not present the normal distribu‐tion (P‐value < .05).

Conclusions

High‐resolution ultrasound permitted the visualization of the three skin layers and the dermal lesions caused by striae. The dermal layer thicknesses with striae were thinner than those without. Therefore, ultrasound 2D imaging has shown to be a promising and financially feasible tool to be used as a noninvasive diagnostic method for evaluating therapeutic protocols used in the treatment of these dermal conditions.
Substantial genetic divergence and lack of recent gene flow support cryptic speciation in a colour polymorphic bumble bee (Bombus bifarius) species complex
Authors: Ghisbain Guillaume , Lozier Jeffrey D. , Rahman Sarthok Rasique , Ezray Briana D. , Tian Li , Ulmer Jonah M. , Heraghty Sam D. , Strange James P. , Rasmont Pierre , Hines Heather M.
Published: January 2020

Phenotypic polymorphism can constitute an inherent challenge for species delimitation. This issue is exemplified in bumble bees (Bombus), where species can exhibit high colour variation across their range, but otherwise exhibit little morphological variation to distinguish them from close relatives. We examine the species status of one of the most abundant North American bumble bees, Bombus bifarius Cresson, which historically comprised two major taxa, bifarius s.s. and nearcticus. These lineages are recognized primarily by red and black variation in their mid‐abdominal coloration; however, a continuum from black (nearcticus) to red (bifarius s.s.) variation has led to their historic synonymization. Integrating mitochondrial and nuclear data and whole‐genome sequencing, we reveal a high level of both mitochondrial and nuclear divergence delimiting two morphologically cryptic species – the red bifarius s.s. and the colour‐variable (black to red) nearcticus. Population genomic analysis supports an absence of recent genomic admixture and a strong population structure between the two clades, even in sympatry. Species distribution models predict partially differentiated niches between the genetically inferred clades with annual precipitation being a leading differentiating variable. The bifarius s.s. lineage also occupies significantly higher elevations, with regions of sympatry being among the highest elevations in nearcticus. Our data also support a subspecies‐level divergence between the broadly distributed nearcticus and the island population vancouverensis. In this paper, we formally recognize the two species, Bombus bifarius Cresson and Bombus vancouverensis Cresson, the latter including the subspecies B. vancouverensis vancouverensis comb.n. and B. vancouverensis nearcticus comb.n., with vancouverensis the name bearer due to year priority.
Pharmacokinetics of platinum and safety evaluation of carboplatin‐impregnated calcium sulfate hemihydrate beads after implantation in healthy cats
Authors: Maxwell Elizabeth A. , Phillips Heidi , Clark‐Price Stuart C. , Vieson Miranda D. , Selmic Laura E. , Schaeffer David J. , Fan Timothy M.
Published: January 2020

Objective

To evaluate the pharmacokinetics (PK) of platinum (Pt) and safety of carboplatin‐impregnated calcium sulfate hemihydrate (C‐I CSH) beads after implantation in healthy cats.

Study design

In vivo experimental study.

Animals

Six healthy adult cats.

Methods

Three C‐I CSH beads were implanted in muscle pockets over the right and left hemithoraces of each cat (~3.9 mg/kg of Pt; 60.4 mg/m2of calculated carboplatin). Hematology and blood chemistry were tested at baseline and 3, 7, 14, and 21 days postimplantation. Serum was analyzed for Pt at specific times from 1 hour to 21 days. Tissue was obtained for histopathology and analysis of Pt at 3, 7, 14, and 21 days at standardized distances from implantation sites.

Results

Platinum was detected in tissues at all times and distances (range, 0.1‐4.19 μg/g). Serum Pt increased up to 2.6 hours (3.25 μg/mL) then decreased sharply. Samples containing muscle had higher Pt compared with samples without muscle (P= .004). Mild hypercalcemia was noted in four cats, and mild inflammatory reaction was noted on histopathology of all samples.

Conclusion

Platinum was released from C‐I CSH beads differentially into surrounding tissues over 21 days. Systemic absorption of Pt was minimal, but mild hypercalcemia occurred.

Clinical significance

Implantation was well tolerated by healthy adult cats. Securing beads within muscle may limit Pt diffusion to targeted tissue. Although Pt concentrations did not achieve levels reported to be cytotoxic for feline sarcoma cells in culture, results provide evidence to support evaluation of efficacy in the tumor microenvironment of cats with locally invasive cancers.
New complex-valued activation functions
Authors: Ozgur Nihal , Taş Nihal , Peters James Francis
Published: January 2020

We present a new type of activation functions for a complex-valued neuralnetwork (CVNN). A proposed activation function is constructed such that itfixes a given ellipse. We obtain an application to a complex-valued Hopfieldneural network (CVHNN) using a special form of the introduced complexfunctions as an activation function. Considering the interesting geometricproperties of the plane curve ellipse such as focusing property, weemphasize that these properties may have possible applications in variousneural networks.
Evaporation of Lubricant Films Subjected to Laminar and Turbulent Boundary Layers
Authors: Gill Stephen James , Tuna Burak A. , Yarusevych Serhiy , Li Xianguo , Shi Fanghui
Published: January 2020

This work investigates experimentally the effects of grid-generated turbulence on the evaporation of thin oil films subjected to laminar, transitional, and turbulent boundary layers. Particle image velocimetry (PIV) is used to characterize flow development within a rectangular duct (20 mm × 40 mm) with a length of 1 m (∼40Dh). The inlet turbulence intensity is manipulated using wire meshes, and experiments are performed for Reynolds numbers based on the duct hydraulic diameter of 10,650, 17,750, and 35,500. Mass transfer measurements are conducted under the characterized boundary layers for oil films with initial thicknesses of 50 μm at a constant substrate temperature of 150 °C. The Reynolds number is shown to have a significant impact on the evaporation rate, whereas varying near-wall turbulence intensity is shown to have little effect for the parameters investigated in this study. This implies that mean wall shear and transport within the viscous sublayer are the predominant parameters governing the convection-limited mass transfer considered in this investigation.
Plasmonic coupling and how standard ellipsometry can feel surface plasmon
Authors: Bortchagovsky Eugene
Published: January 2020

Interacting electromagnetic modes are known to hybridize, and their dispersions split instead of crossing, resulting in an energy gap between them. Such a coupling exists between localized plasmon of nanoparticles and surface plasmon of a supporting metallic substrate. Here, a gold film with gold nanoparticles deposited on the surface was investigated by ellipsometry in the standard configuration with measurements at external reflection and in Kretschmann geometry with measurements at internal reflection. Dispersion relations obtained from measurements in both configurations coincide and demonstrate expected splitting. Surface plasmon on a clean surface do not couple with external light, as such interaction would violate the law of momentum conservation. However, coupling with localized plasmons of deposited nanoparticles allowed excitation of surface plasmon by external light, as confirmed by the results of measurements in the standard ellipsometric configuration.
Mid-IR and UV-Vis-NIR Mueller matrix ellipsometry characterization of tunable hyperbolic metamaterials based on self-assembled carbon nanotubes
Authors: Schöche Stefan , Ho Po-Hsun , Roberts John A. , Yu Shangjie J. , Fan Jonathan A. , Falk Abram L.
Published: January 2020

Mueller matrix ellipsometry over the wide spectral range from the mid-IR to UV is applied to characterize the dielectric function tensor for films of densely packed single-walled carbon nanotubes aligned in the surface plane. These films optically act as metamaterials with an in-plane anisotropic, bulk effective medium response. A parameterized oscillator model is developed to describe electronic interband transitions, π−π⋆ plasmon resonances, and free-carrier absorption. Wide ranges of hyperbolic dispersion are observed and exceptional tuneability of the hyperbolic ranges is demonstrated by comparing results for a film of aligned but unordered carbon nanotubes with a film fabricated under optimized conditions to achieve hexagonally close-packed alignment of the nanotubes. The effect of doping on the optical properties and hyperbolic range is discussed.
Formation and characteristics of mixed lipid/polymer membranes on a crystalline surface-layer protein lattice
Authors: Czernohlavek Christian , Schuster Bernhard
Published: January 2020

The implementation of self-assembled biomolecules on solid materials, in particular, sensor and electrode surfaces, gains increasing importance for the design of stable functional platforms, bioinspired materials, and biosensors. The present study reports on the formation of a planar hybrid lipid/polymer membrane on a crystalline surface layer protein (SLP) lattice. The latter acts as a connecting layer linking the biomolecules to the inorganic base plate. In this approach, chemically bound lipids provided hydrophobic anchoring moieties for the hybrid lipid/polymer membrane on the recrystallized SLP lattice. The rapid solvent exchange technique was the method of choice to generate the planar hybrid lipid/polymer membrane on the SLP lattice. The formation process and completeness of the latter were investigated by quartz crystal microbalance with dissipation monitoring and by an enzymatic assay using the protease subtilisin A, respectively. The present data provide evidence for the formation of a hybrid lipid/polymer membrane on an S-layer lattice with a diblock copolymer content of 30%. The hybrid lipid/polymer showed a higher stiffness compared to the pure lipid bilayer. Most interestingly, both the pure and hybrid membrane prevented the proteolytic degradation of the underlying S-layer protein by the action of subtilisin A. Hence, these results provide evidence for the formation of defect-free membranes anchored to the S-layer lattice.
Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer
Authors: Huang Kuan-Wei , Hsu Fu-Fei , Qiu Jiantai Timothy , Chern Guann-Jen , Lee Yi-An , Chang Chih-Chun , Huang Yu-Ting , Sung Yun-Chieh , Chiang Cheng-Chin , Huang Rui-Lin , Lin Chu-Chi , Dinh Trinh Kieu , Huang Hsi-Chien , Shih Yu-Chuan , Alson Donia , Lin Chun-Yen , Lin Yung-Chang , Chang Po-Chiao , Lin Shu-Yi , Chen Yunching
Published: January 2020

The dual-targeted immunogene therapy that inhibits PD-L1 and provides IL-2 can enhance the therapeutic efficacy of cancer vaccine.
The Euler spiral of rat whiskers
Authors: Starostin Eugene L. , Grant Robyn A. , Dougill Gary , van der Heijden Gert H. M. , Goss Victor G. A.
Published: January 2020

Rat whiskers curve naturally as Euler spirals.
Antibiotic production in
Streptomyces
is organized by a division of labor through terminal genomic differentiation
Authors: Zhang Zheren , Du Chao , de Barsy Frédérique , Liem Michael , Liakopoulos Apostolos , van Wezel Gilles P. , Choi Young H. , Claessen Dennis , Rozen Daniel E.
Published: January 2020

Antibiotic production in
Streptomyces coelicolor
is coordinated by a division of labor through large genome deletions.
Modulation of lymphocyte-mediated tissue repair by rational design of heterocyclic aryl hydrocarbon receptor agonists
Authors: Chen Jiaxuan , Haller Carolyn A. , Jernigan Finith E. , Koerner Steffi K. , Wong Daniel J. , Wang Yiqiang , Cheong Jae Eun , Kosaraju Revanth , Kwan Julian , Park Diane D. , Thomas Beena , Bhasin Swati , De La Rosa Roberto C. , Premji Alykhan M. , Liu Liying , Park Eden , Moss Alan C. , Emili Andrew , Bhasin Manoj , Sun Lijun , Chaikof Elliot L.
Published: January 2020

Heterocyclic aryl hydrocarbon receptor agonists modulate lymphocyte-mediated tissue repair in a murine model of colitis.
Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization
Authors: Forbes Shareen , Bond Andrew R. , Thirlwell Kayleigh L. , Burgoyne Paul , Samuel Kay , Noble June , Borthwick Gary , Colligan David , McGowan Neil W. A. , Lewis Philip Starkey , Fraser Alasdair R. , Mountford Joanne C. , Carter Roderick N. , Morton Nicholas M. , Turner Marc L. , Graham Gerard J. , Campbell John D. M.
Published: January 2020

Human umbilical cord perivascular mesenchymal stromal cells improve vascularization and glycemic control of human islets implanted in mice.
The “cancer flu shot”?
Authors: Jeyasekharan Anand D.
Published: January 2020

Direct injection of an influenza vaccine into tumors in mice increases immune infiltration and prolongs survival.
Organoid optimization: Engineering a better cell therapy to treat type 1 diabetes
Authors: Weaver Jessica D.
Published: January 2020

Islet organoids reaggregated in endothelialized collagen constructs improve engraftment and function in the subcutaneous space in diabetic mice.
Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection
Authors: Webb Brandon J. , Subramanian Aruna , Lopansri Bert , Goodman Bruce , Jones Peter Bjorn , Ferraro Jeffrey , Stenehjem Edward , Brown Samuel M.
Published: January 2020

Clostridioides difficile
infection (CDI) is a health care-associated infection associated with significant morbidity and cost, with highly varied risk across populations. More effective, risk-based prevention strategies are needed. Here, we investigate risk factors for hospital-associated CDI in a large integrated health system. In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (i) hospital-onset and (ii) health care-facility-associated, community-onset CDI.
Evaluation of the WASPLab Segregation Software To Automatically Analyze Urine Cultures Using Routine Blood and MacConkey Agars
Authors: Faron Matthew L. , Buchan Blake W. , Relich Ryan F. , Clark James , Ledeboer Nathan A.
Published: January 2020

Automation of the clinical microbiology laboratory has become more prominent as laboratories face higher specimen volumes and understaffing and are becoming more consolidated. One recent advancement is the use of digital image analysis to rapidly distinguish between chromogenic growth for screening bacterial cultures. In this study, colony segregation software developed by Copan (Brescia, Italy) was evaluated to distinguish between significant growth and no growth of urine cultures plated onto standard blood and MacConkey agars.
Rupture of mitral valve papillary muscle: a rare complication following myocardial infarction
Authors: Sawhney Vinit , Murugan Shivasankar , Iqbal Fahad , Muthumala Amal
Published: January 2020

Here we present a rare clinical presentation of papillary muscle rupture in a 55-year-old man who presented to accident and emergency department with chest pain and was diagnosed as having had a non-ST elevation myocardial infarction. During the admission, he developed papillary muscle rupture due to the myocardial infarction resulting in acute mitral regurgitation. This caused significant haemodynamic compromise needing emergency admission to the intensive care unit and eventually surgery to replace the valve.
Successful liver transplantation for drug-induced vanishing bile duct syndrome
Authors: Hashim Ahmed , Barnabas Ashley , Miquel Rosa , Agarwal Kosh
Published: January 2020

Drug-induced cholestasis has a wide range of clinical presentations, and in a small number of patients, it can progress to severe ductopenia. A 63-year-old woman was referred to our department with progressive cholestasis and hyperbilirubinaemia following a course of flucloxacillin. Despite the comprehensive laboratory, imaging and genetic investigations, no other cause for the cholestasis was demonstrated. Sequential liver biopsies confirmed the development of vanishing bile duct syndrome. She developed significant cachexia and pruritus that did not respond to medical therapy, and hence she was listed for liver transplantation. She underwent liver transplantation 6 months after the initial drug-induced injury. She has remained well with good graft function at 1-year follow-up. The case highlights an extreme form of drug-induced ductopenia and underscores the need for meticulous hepatology input and consideration of liver transplantation in some patients.
Terlipressin-induced ischaemic skin necrosis
Authors: Kulkarni Anand V , Kumar Pramod , Rao Nagaraj P , Reddy Nageshwar
Published: January 2020

Terlipressin is a commonly used drug in hepatology practice for the two most serious complications of cirrhosis, that is, acute oesophageal variceal bleed and hepatorenal syndrome. Acute-on-chronic liver failure (ACLF) is a medical emergency and is frequently associated with acute kidney injury (AKI). Two male patients with alcohol-induced ACLF with high MELD (Model for End-Stage Liver Disease) score presented with AKI. Both were treated with terlipressin infusion. There was no response to terlipressin in these sick patients, and further both patients developed ischaemic skin necrosis and succumbed to multiorgan failure. Continuous infusion of terlipressin is superior to bolus dosing, but we noted that continuous infusion might as well be associated with severe adverse effects in patients with a high MELD score. More extensive prospective studies, including patients with high MELD score, are required to ascertain the safety of terlipressin.
Hybrid Descemet Membrane Endothelial Keratoplasty (H-DMEK): results of a donor insertion pull-through technique using donor stroma as carrier
Authors: Woo Jyh Haur , Htoon Hla Myint , Tan Donald
Published: January 2020

Aim

To evaluate the outcomes and complications of hybrid Descemet membrane endothelial keratoplasty (H-DMEK) using a Descemet stripping automated endothelial keratoplasty (DSAEK) pull-through donor inserter and donor stroma as carrier.

Methods

This was a retrospective interventional case series of eyes with bullous keratopathy (BK) and Fuchs endothelial corneal dystrophy (FECD), which underwent H-DMEK, performed using a bimanual pull-through technique using DSAEK-prepared donor stroma as carrier and the EndoGlide Ultrathin DSAEK donor insertion device. Complex cases with tube shunts, trabeculectomy, aphakia, aniridia, previous vitrectomy, keratoplasty or combined with intraocular lens exchange, were also included. The outcome measures were intraoperative and postoperative complications, best corrected visual acuity (BCVA) and endothelial cell loss after surgery.

Results

Of the 85 eyes from 79 patients, 43.5% (n=37) had BK, 28.2% (n=24) had FECD while 24.7% (n=21) had failed grafts. DMEK was performed in 37 complex eyes (43.5%). Four eyes (4.7%) required rebubbling for graft detachment and two cases of graft failure were observed. A BCVA of 20/25 or better was attained in 44.7% and 57.1% of eyes without pre-existing ocular pathology at 6 and 12 months, respectively. The overall endothelial cell loss was 32.2%±20.5% at 6 months, which improved from 37.2%±20.9% to 24.2%±17.5%, comparing the first 40 and last 45 cases (p=0.012).

Conclusion

Hybrid DMEK offers a controlled ‘pull-through’ technique of donor insertion in the ‘endothelium-in’ configuration, which may be useful especially in complicated eyes. More studies are needed to confirm the long-term endothelial cell loss and graft survival associated with this technique.
Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier’s gangrene
Authors: Yang Jeff Yufeng , Wang Tiansheng , Pate Virginia , Buse John B , Stürmer Til
Published: January 2020

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier’s gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning.

Methods

We used data from IBM MarketScan (2013–2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions.

Results

We identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51–0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04–1.74) to 1.14 (0.86–1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53–6.11) and inpatient diagnoses only (aHR 4.58; 0.99–21.21).

Conclusions

No evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG.

Trial registration number

EUPAS Register Number 30018.
Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease
Authors: Mayeda Laura , Katz Ronit , Ahmad Iram , Bansal Nisha , Batacchi Zona , Hirsch Irl B , Robinson Nicole , Trence Dace L , Zelnick Leila , de Boer Ian H
Published: January 2020

​Objective

Compared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized that glucose time in range (TIR), measured by CGM, is associated with DPN symptoms among participants with type 2 diabetes mellitus (type 2 DM) and moderate-to-severe CKD.

​Research design and methods

We enrolled 105 people with type 2 DM treated with insulin or sulfonylurea, 81 participants with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) and 24 matched control participants with eGFR ≥60 mL/min/1.73 m2. Each participant wore a CGM for two 6-day periods. Calculated glycemic measures included TIR (glucose 70–180 mg/dL) and glucose management indicator (GMI). DPN symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire, with a positive MNSI score defined as ≥2 symptoms.

​Results

Participants with CKD had a mean age of 68 years, diabetes duration 20 years, eGFR 38 mL/min/1.73 m2and HbA1c 7.8%, 61 mmol/mol. Sixty-two participants reported ≥2 DPN symptoms, 51 (63%) with CKD and 11 (46%) controls. Less TIR and higher GMI were associated with higher risk of MNSI questionnaire score ≥2 (OR 1.25 (95% CI 1.02 to 1.52) per 10% lower TIR, and OR 1.79 (95% CI 1.05 to 3.04) per 1% higher GMI, adjusting for age, gender and race). Similar results were observed when analyses were restricted to participants with CKD. In contrast, there was no significant association of HbA1c with DPN symptoms.

​Conclusions

Symptoms of DPN were common among participants with long-standing type 2 DM and CKD. Lower TIR and higher GMI were associated with DPN symptoms.
Impact of transforming mental health services for young people in England on patient access, resource use and health: a quasi-experimental study
Authors: Rocks Stephen , Fazel Mina , Tsiachristas Apostolos
Published: January 2020

Objective

To evaluate the impact of child and adolescent mental health services (CAMHS) transformation in South East England on patient access, resource utilisation and health outcomes.

Design

In an observational study, we use difference-in-differences analysis with propensity score matching to analyse routinely collected patient level data.

Setting

Three CAMHS services in South East England.

Participants

All patients attending CAMHS between April 2012 and December 2018, with more than 57 000 spells of care included.

Main outcome measures

The rate and volume of people accessing CAMHS; waiting times to the first contact and waiting times between the first and second contact; and health outcomes, including the Strengths and Difficulties Questionnaire (SDQ) and the Revised Child Anxiety and Depression Scale (RCADS).

Results

The intervention led to 20% (incidence rate ratio: 1.20; 95% CI: 1.15 to 1.24) more new patients starting per month. There was mixed evidence on waiting times for the first contact. The intervention led to 10% (incidence rate ratio: 1.10; 95% CI: 1.02 to 1.18) higher waiting time for the second contact. The number of contacts per spell (OR: 1.08; 95% CI: 0.94 to 1.25) and the rereferral rate (OR: 1.06; 95% CI: 0.96 to 1.17) were not significantly different. During the post intervention period, patients in the intervention group scored on average 3.3 (95% CI: −5.0 to −1.6) points lower on the RCADS and 1.0 (95% CI: −1.8 to -0.3) points lower on the SDQ compared with the control group after adjusting for the baseline score.

Conclusions

Overall, there are signs that transformation can help CAMHS achieve the objectives of greater access and improved health outcomes, but trade-offs exist among different performance metrics, particularly between access and waiting times. Commissioners and providers should be conscious of any trade-offs when undertaking service redesign and transformation.
Advanced imaging for risk stratification of sudden death in hypertrophic cardiomyopathy
Authors: Ramchand Jay , Fava Agostina M , Chetrit Michael , Desai Milind Y
Published: January 2020

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition, which typically manifests as left ventricular hypertrophy. A small subset of patients with HCM have an increased risk of sudden cardiac death (SCD) from ventricular arrhythmias. Risk of SCD can be effectively reduced following implantation of implantable cardiac defibrillators (ICD), although this treatment carries a risk of complications such as inappropriate shocks. With this in mind, we turn to advances in cardiac imaging to guide risk stratification for SCD and to select the appropriate individual who may benefit from ICD implantation. In this review, we have taken the opportunity to briefly summarise the role of imaging in the diagnosis of HCM before focusing on how specific imaging features influence risk of SCD in patients with HCM.
Performance of cardiovascular risk prediction equations in Indigenous Australians
Authors: Barr Elizabeth Laurel Mary , Barzi Federica , Rohit Athira , Cunningham Joan , Tatipata Shaun , McDermott Robyn , Hoy Wendy E , Wang Zhiqiang , Bradshaw Pamela June , Dimer Lyn , Thompson Peter L , Brimblecombe Julie , O'Dea Kerin , Connors Christine , Burgess Paul , Guthridge Steven , Brown Alex , Cass Alan , Shaw Jonathan E , Maple-Brown Louise
Published: January 2020

Objective

To assess the performance of cardiovascular disease (CVD) risk equations in Indigenous Australians.

Methods

We conducted an individual participant meta-analysis using longitudinal data of 3618 Indigenous Australians (55% women) aged 30–74 years without CVD from population-based cohorts of the Cardiovascular Risk in IndigenouS People(CRISP) consortium. Predicted risk was calculated using: 1991 and 2008 Framingham Heart Study (FHS), the Pooled Cohorts (PC), GloboRisk and the Central Australian Rural Practitioners Association (CARPA) modification of the FHS equation. Calibration, discrimination and diagnostic accuracy were evaluated. Risks were calculated with and without the use of clinical criteria to identify high-risk individuals.

Results

When applied without clinical criteria, all equations, except the CARPA-adjusted FHS, underestimated CVD risk (range of percentage difference between observed and predicted CVD risks: −55% to −14%), with underestimation greater in women (−63% to −13%) than men (−47% to −18%) and in younger age groups. Discrimination ranged from 0.66 to 0.72. The CARPA-adjusted FHS equation showed good calibration but overestimated risk in younger people, those without diabetes and those not at high clinical risk. When clinical criteria were used with risk equations, the CARPA-adjusted FHS algorithm scored 64% of those who had CVD events as high risk; corresponding figures for the 1991-FHS were 58% and were 87% for the PC equation for non-Hispanic whites. However, specificity fell.

Conclusion

The CARPA-adjusted FHS CVD risk equation and clinical criteria performed the best, achieving higher combined sensitivity and specificity than other equations. However, future research should investigate whether modifications to this algorithm combination might lead to improved risk prediction.
Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene
Authors: Valtola Kati , Nino-Quintero Juanita , Hedman Marja , Lottonen-Raikaslehto Line , Laitinen Tomi , Maria Maleeha , Kantola Ilkka , Naukkarinen Anita , Laakso Markku , Kuusisto Johanna
Published: January 2020

Objective

To investigate whether the Ala143Thr variant of the α-galactosidase A gene (A143T/GLA), with conflicting interpretations of pathogenicity, is associated with Fabry cardiomyopathy.

Methods

The index patient, a woman in her 60s with cardiomyopathy, was screened for variants in 59 cardiomyopathy-related genes. A143T/GLA, the only rare variant found, was screened in 10 relatives. GLA activity and lyso-Gb3 levels were measured and echocardiography was performed in 8 of 9 subjects carrying A143T/GLA. Cardiac magnetic resonance (CMR) imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) were performed in four adult A143T/GLA carriers. Endomyocardial biopsy was obtained from two adult A143T/GLA carrying sons of the index patient.

Results

The index patient and her elder son had a pacemaker implantation because of sick sinus syndrome and atrioventricular block. GLA activities were decreased to 25%–40% of normal in both sons and one granddaughter. Lyso-Gb3 levels were elevated in both sons. In CMR, the index patient and her two sons had left ventricular (LV) hypertrophy and/or dilatation. The elder son had late gadolinium enhancement, high CMR-derived T1 time and positive FDG signal in PET/CT in the basal inferolateral LV wall. The younger son had low T1 time and the mother had positive FDG signal in PET/CT in the basal inferolateral LV wall. Endomyocardial biopsy of both sons showed myocardial accumulation compatible with glycolipids in light and electron microscopy, staining with anti-Gb3 antibody available for the younger son. Five female relatives with A143T/GLA had no cardiomyopathy in cardiac imaging.

Conclusions

A143T/GLA is likely a late-onset Fabry cardiomyopathy causing variant with incomplete penetrance.
High CXCR4 expression in adenoid cystic carcinoma of the head and neck is associated with increased risk of locoregional recurrence
Authors: Klein Nulent Thomas J W , van Es Robert J J , Valstar Matthijs H , Smeele Ludwig E , Smit Laura A , Klein Gunnewiek Raquel , Zuithoff Nicolaas P A , de Keizer Bart , de Bree Remco , Willems Stefan M
Published: January 2020

Aim

Treatment options for head and neck adenoid cystic carcinoma (AdCC) are limited in advanced disease. Chemokine receptor type 4 (CXCR4) is present in various tumour types, including AdCC. Upregulation is associated with tumour recurrence and metastasis. New CXCR4-specific diagnostic and therapeutic target agents have recently been available. This study aimed to analyse CXCR4 expression in a cohort of primary head and neck AdCC.

Methods

After histopathological revision, tumour tissues of 73 consecutive patients with AdCC over 1990–2016 were sampled on a tissue microarray. Slides were immunohistochemically stained for CXCR4 and semiquantitatively scored. Associations between protein expression and cliniopathological parameters were tested. HRs were calculated using a Cox proportional hazard model.

Results

Sixty-six tumours could be analysed. CXCR4 expression was present in 81% of the tumours with a median of 29% (IQR 1–70) positive cells. Expression was univariately correlated to perineural growth (Spearman ρ .26, p=0.04) and bone invasion (Spearman ρ .32, p=0.01), but not with tumour grade.

CXCR4 expression in the primary tumour was significantly higher in tumours that recurred as compared with those that did not recur (median 60%, IQR 33–72 vs 12%, IQR 1–70, Kruskal-Wallis p=0.01). After dichotomisation, >25% of CXCR4 expressions proved an independent prognosticator for a reduced recurrence-free survival (RFS) (HR 7.2, 95% CI 1.5 to 72.4, p=0.04).

Conclusion

CXCR4 is expressed in the majority of primary AdCCs and independently correlated to worse RFS, suggesting CXCR4 as a target for imaging and therapy purposes in patients with advanced AdCC.
Defining current gaps in quality measures for cancer immunotherapy: consensus report from the Society for Immunotherapy of Cancer (SITC) 2019 Quality Summit
Authors: Pai Sara , Blaisdell David , Brodie Rachel , Carlson Robert , Finnes Heidi , Galioto Michele , Jensen Roxanne E , Valuck Tom , Sepulveda Antonia R , Kaufman Howard L
Published: January 2020

Background

Quality measures are important because they can help improve and standardize the delivery of cancer care among healthcare providers and across tumor types. In an environment characterized by a rapidly shifting immunotherapeutic landscape and lack of associated long-term outcome data, defining quality measures for cancer immunotherapy is a high priority yet fraught with many challenges.

Methods

Thus, the Society for Immunotherapy of Cancer convened a multistakeholder expert panel to,first, identify the current gaps in measures of quality cancer care delivery as it relates to immunotherapy and to,second, advance priority concepts surrounding quality measures that could be developed and broadly adopted by the field.

Results

After reviewing the existing quality measure landscape employed for immunotherapeutic-based cancer care, the expert panel identified four relevant National Quality Strategy domains (patient safety, person and family-centered care, care coordination and communication, appropriate treatment selection) with significant gaps in immunotherapy-based quality cancer care delivery. Furthermore, these domains offer opportunities for the development of quality measures as they relate to cancer immunotherapy. These four quality measure concepts are presented in this consensus statement.

Conclusions

This work represents a first step toward defining and standardizing quality delivery of cancer immunotherapy in order to realize its optimal application and benefit for patients.
Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study
Authors: Derman Benjamin A , Zha Yuanyuan , Zimmerman Todd M , Malloy Rebecca , Jakubowiak Andrzej , Bishop Michael R , Kline Justin
Published: January 2020

Background

Progression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.

Methods

We performed a randomized study to evaluate two methods of Treg depletion in patients with MM undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 monoclonal antibody (basiliximab 20 mg IV) was administered on day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. Tregs were depleted from autologous stem cell (ASC) grafts with anti-CD25 microbeads and the CliniMACS device in the ex vivo Treg depletion (EVTRD) arm.

Results

Fifteen patients were enrolled, five in each arm. The conditioning regimen was melphalan 200 mg/m2. Primary objectives included assessments of efficiency of IVTRD/EVTRD, kinetics of Treg depletion and recovery following ASCT, and safety. EVTRD removed 90% of CD4+CD25+cells from ASC grafts. IVTRD and EVTRD led to reductions in Treg frequency between days +7 and +90 post-transplant compared with the control (p=0.007 and p<0.001, respectively).

Conclusions

IVTRD and EVTRD are feasible and significantly reduce and delay Treg recovery post-ASCT for MM, and serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes.

Trial registration number

NCT01526096.
Analysis of the non-linear beam dynamics at top energy for the CERN Large Hadron Collider by means of a diffusion model
Authors: Bazzani A. , Giovannozzi M. , Maclean E. H.
Published: January 2020

In this paper, the experimental results of the recent dynamic aperture at top energy for the CERN Large Hadron Collider are analysed by means of a diffusion model whose novelty consists of deriving the functional form of the diffusion coefficient from Nekhoroshev theorem. This theorem provides an optimal estimate of the remainder of perturbative series for Hamiltonian systems. As a consequence, a three-parameter diffusion model is built that reproduces the experimental results with a high level of accuracy. A detailed discussion of the physical interpretation of the proposed model is also presented.
Thermally excited quasiparticles in metals, dispersion forces, and the thermal anomaly
Authors: Henkel Carsten
Published: January 2020

We provide a brief review of the contribution of thermally excited carriers to dispersion forces. In a metal, these carriers generate charge and current fluctuations whose spectral frequencies are comparable to [Formula: see text]. They are very likely responsible for the “plasma vs. Drude” anomaly.
The production of ground-related hazard maps to aid risk management of the Highways England Strategic Road Network Hazard maps for Highways England
Authors: Neville Jonny , Power Christopher , Spink Tim , Grant David , Patterson David
Published: January 2020

As part of a coordinated programme of knowledge improvement tasks, Highways England commissioned Mott MacDonald to research, develop and implement a series of maps to communicate clearly the threat posed by ground-related hazards to the Strategic Road Network (SRN) of England. Events associated with a number of hazards have occurred in the recent past. Understanding the presence, and relative likelihood of occurrence, of these hazards over the 7000 km of the SRN is an essential risk management activity. The maps draw on readily available data sources held on the Geotechnical Data Management System of Highways England (HAGDMS) and have been deliberately created to be open and simple, to convey the hazards to users who may not be specialists in engineering geology. This paper presents the development, validation and application of the hazard maps.

Thematic collection
: This article is part of the Ground-related risk to transportation infrastructure collection available at:
https://www.lyellcollection.org/cc/Ground-related-risk-to-transportation-infrastructure
Hardware Trojan Mitigation in Pipelined MPSoCs
Authors: Malekpour Amin , Ragel Roshan , Li Tuo , Javaid Haris , Ignjatovic Aleksandar , Parameswaran Sri
Published: January 2020

Multiprocessor System-on-Chip (MPSoC) has become necessary due to the the billions of transistors available to the designer, the need for fast design turnaround times, and the power wall. Thus, present embedded systems are designed with MPSoCs, and one possible way MPSoCs can be realized is through Pipelined MPSoC (PMPSoC) architectures, which are used in applications from video surveillance to cryptosystems. Hardware Trojans (HTs) on PMPSoCs are a significant concern due to the damage caused by their stealth. An adversary could use HTs to extract secret information (data leakage) to modify functionality/data (functional modification) or make PMPSoCs deny service. In this article, we present PMPGuard, a mechanism that (1) detects the presence of hardware Trojans in Third Party Intellectual Property (3PIP) cores of PMPSoCs by continuous monitoring and testing and (2) recovers the system by switching the infected processor core with another one. We designed, implemented, and tested the system on a commercial cycle accurate multiprocessor simulation environment. Compared to the state-of-the-art system-level techniques that use Triple Modular Redundancy (TMR) and therefore incur at least 3× area and power overheads, our proposed system incurs about 2× area and 1.5× power overheads without any adverse impact on throughput.
A Facile Method to Prepare Ultrafine Pd Nanoparticles Embedded into N-Doped Porous Carbon Nanosheets as Highly Efficient Electrocatalysts for Oxygen Reduction Reaction
Authors: Zhang Shenzhi , Wang Likai , Fang Liping , Tian Yali , Tang Yi , Niu Xueliang , Hao Yupeng , Li Zhongfang
Published: January 2020

To explore cheap alternatives for platinum electrocatalysts, many strategies have been widely studied. And Pd is regarded as a ideal alternative catalyst due to its high stability and catalytic activity. In this work, we designed a facile method to prepare a highly efficient electrocatalyst in which ultrafine Pd nanoparticles are embedded into N-doped porous carbon nanosheets for oxygen reduction reaction (ORR) in alkaline and acid media. A series of products with different Pd quantities were in situ prepared in the absence of additional reductant and capping agents by varying the addition of PdCl2, while the morphology and the structural features of products through X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD) and transmission electron microscopy (TEM) and BET measurements show that Pd nanoparticles are embedded into N-doped porous carbon nanosheets. Obviously, the sample of Pd-NCs-3 demonstrate the best electrocatalytic activity and remarkable long-term stability among the series, which is superior to that of commercial Pd/C and comparable to that of commercial Pt/C for ORR in alkaline and acid media. The results provides a novel strategy for the rational development of cheap alternatives for platinum electrocatalysts.