bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between Mid-Term Results of Total Knee Arthroplasty with Single-Radius versus Multiple-Radii Posterior-Stabilized Prostheses
Authors: Luo Zhenyu , Zhou Kai , Wang Haoyang , Pei Fuxing , Zhou Zongke
Published: July 2020

Single-radius (SR) prostheses and multiple-radii (MR) prostheses have different theoretical advantages; however, few comparative studies have been reported. The aim of the study was to compare mid-term clinical, radiological, and survival outcomes of SR and MR posterior-stabilized prostheses in total knee arthroplasty (TKA). Two hundred consecutive patients who underwent TKA between January 2012 and July 2013 were enrolled in the SR group (100 patients) and an MR group (100 patients), with a minimum follow-up of 5 years. Functional, radiological, satisfaction, and survival rates were evaluated. There was a significantly higher range of motion (ROM) in the SR group than in the MR group (flexion, 123.65 ± 10.12 degrees vs. 115.52 ± 10.03 degrees, p < 0.001). Quadriceps strength (3.05 ± 0.43 vs. 2.68 ± 0.58 kg, p = 0.025) and chair test results (80 [93.02%] vs. 69 [83.13%], p = 0.027) were better in the SR group than in the MR group. The SR group also had significantly less anterior knee pain (6 [6.98%] vs. 15 [18.07%], p < 0.05) and a better satisfaction rate than those in the MR group. No significant differences were observed in clinical scale scores such as Hospital for Special Surgery (HSS), Knee Society Score (KSS), and Short-Form 12 (SF-12), radiological results in terms of component position and radiolucent lines. The Kaplan–Meier survival curve estimates at 5 years were not significantly different (96.91% [95% confidence interval [CI]: 93.5–99.5%] vs. 94.86% [95% CI: 90.6–98.6%], p = 0.4696). The SR prosthesis design was better than that of the MR in terms of ROM, reduced anterior knee pain, contributions to better recovery of the extension mechanism, and higher satisfaction rates. The SR had similar results in clinical scales such as HSS, KSS, SF-12, radiological, or survival results to MR prostheses. More accurate measurements and longer-term follow-up are required.
A high-sensitivity flexible electric skin using a liquid-core PVDF fiber
Authors: Jiang Yani , Wu Jiachen , Huang Huiyu , Wang Rumeng , Zheng Zaixiang , Gong Junjie , Guo Guangming , Wang Changlong , Bian Yixiang
Published: July 2020

An electronic skin (ES) is developed by embedding a liquid-core poly(vinylidene fluoride) fiber into a silicone rubber. The experimental results show that the ES can detect the waveform, frequency, amplitude, and other parameters of the surface vibration pressure. The ES can sense the surface pressure amplitude over a range of 1.5–2.5 kPa and exhibits a sensitivity of 0.0472 fC/Pa when the pressure is less than 60 Pa. The resonant frequency of the ES is 0.4 Hz. The ES can also detect the elongation strain, and its sensitivity is 0.0058 fC/με. The ES has the characteristics of flexibility, high sensitivity, and a wide measuring range. Therefore, the ES can be used as a robot finger skin, which enables the robot to have touch perception capabilities.
Two-photon phase-sensing with single-photon detection
Authors: Vergyris Panagiotis , Babin Charles , Nold Raphael , Gouzien Elie , Herrmann Harald , Silberhorn Christine , Alibart Olivier , Tanzilli Sébastien , Kaiser Florian
Published: July 2020

Path-entangled multi-photon states allow optical phase-sensing beyond the shot-noise limit, provided that an efficient parity measurement can be implemented. Realizing this experimentally is technologically demanding, as it requires coincident single-photon detection proportional to the number of photons involved, which represents a severe challenge for achieving a practical quantum advantage over classical methods. Here, we exploit advanced quantum state engineering based on superposing two photon-pair creation events to realize a new approach that bypasses this issue. In particular, optical phase shifts are probed with a two-photon quantum state whose information is subsequently effectively transferred to a single-photon state. Notably, without any multiphoton detection, we infer phase shifts by measuring the average intensity of the single-photon beam on a photodiode, in analogy to standard classical measurements. Importantly, our approach maintains the quantum advantage: twice as many interference fringes are observed for the same phase shift, corresponding to N = 2 path-entangled photons. Our results demonstrate that the advantages of quantum-enhanced phase sensing can be fully exploited in standard intensity measurements, paving the way toward resource-efficient and practical quantum optical metrology.
Zones of soft and hard self-excitation in gyrotrons: Generalized approach
Authors: Nusinovich Gregory S. , Chen Xianfei , Dumbrajs Olgierd , Xiao Houxiu , Han Xiaotao
Published: July 2020

It is known that the gyrotron theory is developed in a general form that allows one to draw many important conclusions about gyrotron operation, which are valid for gyrotrons operating in arbitrary modes, at arbitrary frequencies, and driven by electron beams with different voltages and currents. One of important issues in this theory is the analysis of possible start-up scenarios, i.e., the methods allowing, first, to excite the desired mode prior to competitors in the region of soft self-excitation of this mode and, then, drive it into the zone of hard self-excitation where, as a rule, the operation with high efficiency is possible. So far, in all studies, these zones of soft and hard self-excitation were defined for specific voltages. In the present paper, it is shown how one can determine these zones in a more general manner that makes the results applicable to gyrotrons operating at arbitrary voltages. The study also includes consideration of the no-start-current zones and the role of electron velocity spread.
Early stage degradation related to dislocation evolution in neutron irradiated AlGaN/GaN HEMTs
Authors: Xu Jianxing , Wang Rong , Zhang Liang , Zhang Shiyong , Zheng Penghui , Zhang Ying , Song Yu , Tong Xiaodong
Published: July 2020

The early stage degradation of electrical properties in AlGaN/GaN high electron mobility transistors (HEMTs) under fast neutron irradiation is studied. After the 1 MeV neutron irradiation at a low fluence of 1 × 1014 neutrons/cm2, the reverse leakage current decreases while the output and transfer characteristics remain unchanged, which cannot be explained by the previously reported high-fluence degradation model. By employing temperature-dependent gate leakage current measurements, we show that the dislocation related Poole–Frenkel (PF) emission dominates the gate leakage mechanism before and after irradiation whereas the barrier height for electron emission to conductive dislocation increases after the neutron irradiation. A model with the evolution of dislocation from the VGa-decorated configuration to the pure configuration is proposed to describe the degradation of AlGaN/GaN HEMTs at the low-fluence early stage neutron irradiation. This model enriches the understanding of the degradation mechanism of neutron irradiated AlGaN/GaN HEMTs.
The bond dissociation energy of VO measured by resonant three-photon ionization spectroscopy
Authors: Merriles Dakota M. , Sevy Andrew , Nielson Christopher , Morse Michael D.
Published: July 2020

The predissociation threshold of VO has been measured using resonant three-photon ionization (R3PI) spectroscopy. Given the high density of electronic states in the molecule, it is argued that the molecule dissociates rapidly as soon as the thermochemical bond dissociation energy (BDE) is exceeded, allowing the measured predissociation threshold to be assigned as the BDE. This is the first time a BDE has been measured using the R3PI method. The first photon is provided by an optical parametric oscillator (OPO) laser that promotes VO into a high-energy, discrete vibronic state. A tunable dye laser then excites the molecule further to a resonant state close to the dissociation limit where there is a quasi-continuum of states. A second photon from the same dye laser pulse ionizes the molecule, generating VO+ ions. The dye laser is then scanned to higher energies, and when the energy of one OPO photon plus one dye photon exceeds the BDE, the molecule dissociates before another dye photon can be absorbed to induce ionization. The combined photon energy at the sharp drop in the ion signal is assigned as the BDE. The experiment has been repeated using four different intermediate states, all yielding the same BDE, D0(VO) = 6.545(2) eV. Using thermochemical cycles, a revised value for the BDE of cationic VO is obtained, D0(V+–O) = 6.053(2) eV. The 0 K enthalpy of formation for VO(g) is also derived as ΔfH0K0VO(g) = 128.6(1.0) kJ mol−1. Previous spectroscopic and thermochemical studies of VO are reviewed.
Tuning thermo-magnetic properties of dilute-ferromagnet multilayers using RKKY interaction
Authors: Polishchuk Dmytro M. , Persson Milton , Kulyk Mykola M. , Holmgren Erik , Pasquale Gabriele , Korenivski Vladislav
Published: July 2020

We demonstrate a 20-fold enhancement in the strength of the Ruderman–Kittel–Kasuya–Yosida interlayer exchange in dilute-ferromagnet/normal-metal multilayers by incorporating ultrathin Fe layers at the interfaces. Additionally, the resulting increase in the interface magnetic polarization profoundly affects the finite-size effects, sharpening the Curie transition of the multilayer, while allowing us to separately tune its Curie temperature via intra-layer magnetic dilution. These results should be useful for designing functional materials for applications in magnetocaloric micro-refrigeration and thermally assisted spin-electronics.
Visual impairment among Aboriginal and Torres Strait Islander patients attending an Australian Indigenous primary health service: a cross-sectional study
Authors: Lakhan Prabha , Osuagwu Uchechukwu L. , Askew Deborah , Hayman Noel , Spurling Geoffrey
Published: July 2020

This cross-sectional study aimed to identify the period prevalence of visual impairment (VI) and blindness among Aboriginal and Torres Strait Islander people attending an Indigenous urban primary healthcare service, eye care practitioner referrals for those with VI and any opportunities to improve care delivery. Visual acuity (VA) examinations, using a Snellen chart, are performed as part of routine annual health assessments offered to children and adults. This study included patients aged ≥5 years (n=1442) who had a health assessment conducted between 1 January 2015 and 31 December 2016 and provided consent for the use of their health assessment information for research. Of patients with available data, 2.4% (33/1374) experienced VI, defined as presenting VA worse than 6/12 to 6/60 in the better-seeing eye. VI was more common in those aged ≥60 years (14/136; 10.3%) and was significantly associated with increasing age (P<0.001). No patients experienced blindness, defined as presenting VA worse than 6/60 in the better-seeing eye. All patients with VI were aged ≥16 years. Nine (27%) of the 33 patients with VI in the better-seeing eye were referred to an optometrist or an ophthalmologist. The low period prevalence of VI and no blindness in this study are positive findings. The findings also indicate that routine VA testing of older adults, especially those aged ≥60 years, should be conducted to avoid missing those not having an annual health assessment.
Commissioning for health and community sector reform: perspectives on change from Victoria
Authors: Silburn Kate , Lewis Virginia
Published: July 2020

Commissioning health and community services is a complex task involving planning, purchasing and monitoring services for a population. It is particularly difficult when attempting system-level reform, and many barriers to effective commissioning have been documented. In Victoria, the state government has operated as a commissioner of many services, including mental health community support and alcohol and other drug treatment services. This study investigated the perceived consequences of a reform process in these two sectors after recommissioning was used as a mechanism to achieve sector-wide redesign. Semi-structured interviews were conducted with 23 senior staff from community health, mental health and drug and alcohol services 6 months after implementation. The process was affected by restructuring in the commissioning department resulting in truncation of preparatory planning and technical work required for system design. Consequently, reform implementation was reportedly chaotic, costly to agencies and staff, and resulted in disillusionment of enthusiastic reform supporters. Negative service system impacts were produced, such as disruption of collaborative and/or comprehensive models of care and strategies for reaching marginalised groups. Without careful planning and development commissioning processes can become over-reliant on competitive tendering to produce results, create significant costs to service providers and engender system-level issues with the potential to disrupt innovative models focused on meeting client needs.
Quality and targeting of new referrals for ocular complications of diabetes from primary care to a public hospital ophthalmology service in Western Sydney, Australia
Authors: Ford Belinda , Keay Lisa , Angell Blake , Hyams Stephanie , Mitchell Paul , Liew Gerald , White Andrew
Published: July 2020

Patients with diabetes require regular examination for eye disease, usually in primary care settings. Guidelines recommend patients with at least moderate non-proliferative diabetic retinopathy (NPDR) be referred to an ophthalmologist for treatment; however, poorly targeted referrals lead to access blocks. The quality of new referrals associated with diabetes to a public ophthalmology service in Sydney, New South Wales, Australia, were assessed for referral completeness and targeting. A cross-sectional audit of medical records for new patients referred to Westmead Hospital Eye Clinic in 2016 was completed. Completeness of medical and ophthalmic information in referrals and subsequent patient diagnosis and management in 2016–17 was recorded. Sub-analyses were conducted by primary care referrer type (GP or optometrist). In total, 151 new retinopathy referrals were received; 12% were sent directly to a treatment clinic. Information was incomplete for diabetes status (>60%), medical (>50%) and ophthalmic indicators (>70%), including visual acuity (>60%). GP referrals better recorded medical, and optometrists (37%) ophthalmic information, but information was still largely incomplete. Imaging was rarely included (retinal photos <1%; optical coherence tomography <3%). Median appointment wait-time was 124 days; 21% of patients received treatment (laser or anti-vascular endothelial growth factor) at this or the following encounter. Targeting referrals for ocular complication of diabetes to public hospitals needs improvement. Education, feedback and collaborative care mechanisms should be considered to improve screening and referral in primary care.
Gene and protein expression of connexins 37 and 43 in cumulus–oocytes complexes throughout the canine oestrous cycle
Authors: De los Reyes Monica , Palomino Jaime , Gallegos Carola , Espinoza Roberto , Dettleff Phillipe , Peralta Oscar A. , Parraguez Victor H. , Ramirez George
Published: July 2020

The aim of this study was to evaluate the expression of connexin (Cx) 37 and Cx43 in canine cumulus–oocyte complexes (COCs) during the oestrous cycle. Cx localisation was analysed by immunohistochemistry and immunofluorescence, whereas protein and gene expression was evaluated by western blotting and quantitative polymerase chain reaction respectively; comparisons were made using analysis of variance. Both Cx37 and Cx43 were expressed in all follicular stages; Cx43 was identified in cumulus cells and Cx37 was identified in cumulus cells, zonae pellucida and oocytes. Immunofluorescence analyses showed that Cx37 remained unchanged during the preovulatory stage but decreased after ovulation, whereas Cx43 remained unchanged before and after ovulation. Cx43 transcripts increased (P<0.05) during anoestrus and dioestrus in medium-sized follicles but remained unaltered during the pro-oestrus and antral stages during oestrus, before and after ovulation. Cx37 mRNA levels decreased in ovulated COCs (P<0.05). The highest levels of Cx37 protein (P<0.05) were detected in the preantral stage during anoestrus. In contrast, strong Cx43 signals were detected in oestrus and in medium-sized antral follicles in dioestrus (P<0.05). Overall, we demonstrated that Cx37 and Cx43 exhibit different expression patterns, suggesting specific roles throughout growth. Maintenance of Cx expression before ovulation indicates the involvement of Cx37 and Cx43 in the prolonged meiotic arrest.
Valency coercion in Italian
Authors: Busso Lucia , Lenci Alessandro , Perek Florent
Published: July 2020

The paper investigates valency coercion effects in Italian by means of an acceptability rating task on nine argument structure constructions. The experimental design followsPerek & Hilpert (2014)in presenting three conditions: grammatical, impossible and coercion stimuli. This design allows us to test several factors: the acceptability of creative coerced structures, the role of age and – most importantly – the influence of the construction itself. Results overall confirm our hypotheses: valency coercion is identified as an intermediate level between grammaticality and ungrammaticality, with varying degrees of “coercibility” across constructions. An influence of age is not in evidence for coercion sentences, suggesting that the systematic variation in acceptability is due to the influence of different constructions. We propose that coercion resolution results from the interaction of constructional and lexical semantics.
Moving Time vs. Frame-relative motion
Authors: Moore Kevin Ezra
Published: July 2020

There is an elaborate analogy between Moving Time (composed of primary metaphors; e.g. Christmas is
approaching) and Frame-relative Fictive Motion (e.g. Your destination is approaching). It has been
suggested that this analogy could be involved in the motivation of Moving Time. However, a semantic frame analysis that includes
all stages of the motion event shows that this analogy could not be involved in the motivation of Moving Time. It is further
argued that Moving Time and Frame-relative Fictive Motion are instances of different types of cognitive-semantic structure. Moving
Time is a selective integration of concepts from frames that do not share elements with each other, whereas Frame-relative Fictive
Motion presupposes a single semantic frame. For the purpose of distinguishing fictive motion from primary metaphor (e.g. Moving
Time), Coextension-path and Pattern-path fictive motion are studied in addition to Frame-relative. These three types of fictive
motion can be distinguished from primary metaphor because they involve the integration of concepts from frames that share specific
structure, whereas primary metaphor involves frames that do not share specific structure.

In a preliminary classification of fictive motion as a type of metaphor, all three types of fictive motion
discussed may be classified as resemblance-based metaphors. Coextension-path and Frame-relative fictive motion are also motivated
by correlations in experience. These correlations, however, are different in kind from those that motivate primary metaphor.
Are Chinese immigrants in Cameroon perceived as a threat?
Authors: Nshom Elvis , Arzamastseva Elizaveta
Published: July 2020

Chinese immigration to Cameroon has significantly increased within the last two decades. Members of the Cameroonian society have received Chinese presence with mixed feelings. Recent reports indicate that negative attitudes towards Chinese immigrants are on the rise. In a sample of 501 young people, ranging from 17 to 33 years old, this study specifically uses the integrated threat theory of prejudice to analyse the extent to which attitudes towards Chinese immigrants in Cameroon are predicted by the perception of threat. According to the most recent conceptualization of the integrated threat theory, there are two main types of threat that predict negative attitudes towards outgroups. These include realistic threat and symbolic threat. This study found that, a threat was a significant predictor of negative attitudes towards Chinese immigrants. However, individually, a realistic threat was the only threat that significantly predicted negative attitudes towards Chinese immigrants. Implications and future directions are discussed.
High transmission from 2D periodic plasmonic finite arrays with sub-20 nm gaps realized with Ga focused ion beam milling
Authors: Pisano Filippo , Balena Antonio , Kashif Muhammad Fayyaz , Pisanello Marco , de Marzo Gaia , Algieri Luciana , Qualtieri Antonio , Sileo Leonardo , Stomeo Tiziana , D’Orazio Antonella , De Vittorio Massimo , Pisanello Ferruccio , Grande Marco
Published: July 2020

Fabricating plasmonic nanostructures with good optical performances often requires lengthy and challenging patterning processes that can hardly be transferred to unconventional substrates, such as optical fiber tips or curved surfaces. Here we investigate the use of a single Ga focused ion beam process to fabricate 2D arrays of gold nanoplatelets for nanophotonic applications. While observing that focused ion beam milling of crossing tapered grooves inherently produces gaps below 20 nm, we provide experimental and theoretical evidence for the spectral features of grooves terminating with a sharp air gap. We show that transmission near 10% can be obtained via two-dimensional nano-focusing in a finite subset of 2D arrays of gold nanoplatelets. This enables the application of our nanostructure to detect variations in the refractive index of thin films using either reflected or transmitted light when a small number of elements are engaged.
Diel scent and nectar rhythms of an African orchid in relation to bimodal activity patterns of hawkmoth pollinators
Authors: Balducci Marco G , Van der Niet Timotheüs , Johnson Steven D
Published: July 2020

Background and Aims

The temporal dimensions of floral adaptation to pollinators are not yet well understood, partly because we lack accurate information on the diel rhythms of flower visitation for many pollinators. We investigated whether diel patterns of pollinator visitation to flowers of the African woodland orchid Bonatea polypodantha are synchronized with rhythms of floral anthesis, scent emission and nectar availability.

Methods

Direct observations and motion-activated cameras were used to identify pollinators of B. polypodantha and to document their activity periods. The timing of pollinaria removal from flowers, emission of scent and availability of nectar was also measured.

Results

We found that B. polypodantha is pollinated exclusively by short-tongued hawkmoths. Pollinaria of the orchid are affixed between the labial palps of the moths and brush over the protruding stigmatic arms. The flowers also receive visits by long-tongued hawkmoths, but these act as nectar thieves. Tracking of pollinaria removal from flowers confirmed that pollination occurs only at night. Camera footage revealed a striking crepuscular pattern of foraging by short-tongued hawkmoths with peaks of activity during the twilight periods at dusk and at dawn. In contrast, long-tongued hawkmoths were found to visit flowers throughout the night. Flowers of B. polypodantha exhibit unimodal peaks of anthesis, scent emission (dominated by nitrogenous aromatics) and nectar availability before or around dusk.

Conclusions

Flowers of B. polypodantha are pollinated exclusively by short-tongued hawkmoths, which show crepuscular foraging activity at dusk and dawn. Floral phenophases of the orchid are closely synchronized with the peak of pollinator activity at dusk.
Cognitive Telerehabilitation with Transcranial Direct Current Stimulation Improves Cognitive and Emotional Functioning Following a Traumatic Brain Injury: A Case Study
Authors: Eilam-Stock Tehila , George Allan , Charvet Leigh E
Published: July 2020

Objective

Cognitive deficits following a traumatic brain injury (TBI) are a leading cause of disability in young adults and there is a critical need for novel approaches to improve cognitive outcomes in TBI survivors. Transcranial direct current stimulation (tDCS) paired with cognitive remediation has emerged as a viable, cost-effective, noninvasive approach for treating cognitive impairments in a wide variety of neurological conditions. Here, we report the first case study utilizing remotely supervised tDCS (RS-tDCS) protocol paired with cognitive remediation in a 29-year-old man with persisting cognitive and emotional sequelae following TBI.

Method

Neuropsychological measures were administered before and after the patient completed 20 daily sessions of RS-tDCS (2.0 mA × 20 minutes, left anodal dorsolateral prefrontal cortex montage). During the daily stimulation period, he completed adaptive cognitive training. All treatment procedures were delivered at home and monitored in real time via videoconference with a study technician.

Results

Following 20 RS-tDCS and cognitive training sessions, he had significant improvements (>1 SD) on tests of attention and working memory, semantic fluency, and information processing speed. Mood was also improved.

Conclusions

This is the first demonstration of at-home telerehabilitation with RS-tDCS and cognitive training to improve cognitive outcomes following TBI.
Machine Boss: rapid prototyping of bioinformatic automata
Authors: Silvestre-Ryan Jordi , Wang Yujie , Sharma Mehak , Lin Stephen , Shen Yolanda , Dider Shihab , Holmes Ian
Published: July 2020

Motivation

Many software libraries for using Hidden Markov Models in bioinformatics focus on inference tasks, such as likelihood calculation, parameter-fitting and alignment. However, construction of the state machines can be a laborious task, automation of which would be time-saving and less error-prone.

Results

We present Machine Boss, a software tool implementing not just inference and parameter-fitting algorithms, but also a set of operations for manipulating and combining automata. The aim is to make prototyping of bioinformatics HMMs as quick and easy as the construction of regular expressions, with one-line ‘recipes’ for many common applications. We report data from several illustrative examples involving protein-to-DNA alignment, DNA data storage and nanopore sequence analysis.

Availability and implementation

Machine Boss is released under the BSD-3 open source license and is available from http://machineboss.org/.

Supplementary information

Supplementary data are available at Bioinformatics online.
proABC-2: PRediction of AntiBody contacts v2 and its application to information-driven docking
Authors: Ambrosetti Francesco , Olsen Tobias Hegelund , Olimpieri Pier Paolo , Jiménez-García Brian , Milanetti Edoardo , Marcatilli Paolo , Bonvin Alexandre M J J
Published: July 2020

Motivation

Monoclonal antibodies are essential tools in the contemporary therapeutic armory. Understanding how these recognize their antigen is a fundamental step in their rational design and engineering. The rising amount of publicly available data is catalyzing the development of computational approaches able to offer valuable, faster and cheaper alternatives to classical experimental methodologies used for the study of antibody–antigen complexes.

Results

Here, we present proABC-2, an update of the original random-forest antibody paratope predictor, based on a convolutional neural network algorithm. We also demonstrate how the predictions can be fruitfully used to drive the docking in HADDOCK.

Availability and implementation

The proABC-2 server is freely available at: https://wenmr.science.uu.nl/proabc2/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Selection of side of ovulation by intraovarianism in Bos taurus heifers†
Authors: Ginther O J
Published: July 2020

Intraovarianism refers to mechanisms within an ovary that affect the local follicle and luteal dynamics and is well-represented in heifers by greater frequency of ovulation from the right ovary (RO) than the left ovary (LO). On average, the RO has more 6-mm follicles than the LO before one follicle is selected to deviate in diameter and become the future ovulatory follicle. Therefore, the ovulatory follicle is more frequently selected from the RO. More follicles in the RO likely develop before birth as indicated by greater weight of the RO with more 0.3- to 4.8-mm follicles in recently born calves. It has been proposed that differences in intraovarianism between sides are a consequence of differences between sides in the inherent intraovarian angioarchitecture. The frequency of the pair of ovulations at the beginning and end of 900 interovulatory intervals (IOI) was lowest for the left/left (LL) pair (16%) and higher and similar among the RR, LR, and RL pairs (28% each). The lower frequency of LO ovulation was entirely a function of the LL pair as indicated by the lower frequency of the LL than RR pairs without a difference among the RR, LR, and RL pairs. Ovulations from the opposite sides at the beginning and end of an IOI (LR and RL pairs) would not have contributed to a difference in ovulation frequency between LO and RO. In conclusion, the greater frequency of RO (56%) than LO (44%) ovulation was mathematically and functionally a direct consequence of the low frequency of the LL pair of ovulations.
Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial
Authors: Mitjà Oriol , Corbacho-Monné Marc , Ubals Maria , Tebé Cristian , Peñafiel Judith , Tobias Aurelio , Ballana Ester , Alemany Andrea , Riera-Martí Núria , Pérez Carla A , Suñer Clara , Laporte Pep , Admella Pol , Mitjà Jordi , Clua Mireia , Bertran Laia , Sarquella Maria , Gavilán Sergi , Ara Jordi , Argimon Josep M , Casabona Jordi , Cuatrecasas Gabriel , Cañadas Paz , Elizalde-Torrent Aleix , Fabregat Robert , Farré Magí , Forcada Anna , Flores-Mateo Gemma , Muntada Esteve , Nadal Núria , Narejos Silvia , Nieto Aroa , Prat Nuria , Puig Jordi , Quiñones Carles , Reyes-Ureña Juliana , Ramírez-Viaplana Ferran , Ruiz Lidia , Riveira-Muñoz Eva , Sierra Alba , Velasco César , Vivanco-Hidalgo Rosa Maria , Sentís Alexis , G-Beiras Camila , Clotet Bonaventura , Vall-Mayans Martí
Published: July 2020

Background

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.

Methods

Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days.

Results

A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported.

Conclusions

In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.
Generic Protocols for the Analytical Validation of Next-Generation Sequencing-Based ctDNA Assays: A Joint Consensus Recommendation of the BloodPAC’s Analytical Variables Working Group
Authors: Godsey James H , Silvestro Angela , Barrett J Carl , Bramlett Kelli , Chudova Darya , Deras Ina , Dickey Jennifer , Hicks James , Johann Donald J , Leary Rebecca , Lee Jerry S H , McMullen Joe , McShane Lisa , Nakamura Katherine , Richardson Aaron O , Ryder Matthew , Simmons John , Tanzella Kelli , Yee Laura , Leiman Lauren C
Published: July 2020

Liquid biopsy, particularly the analysis of circulating tumor DNA (ctDNA), has demonstrated considerable promise for numerous clinical intended uses. Successful validation and commercialization of novel ctDNA tests have the potential to improve the outcomes of patients with cancer. The goal of the Blood Profiling Atlas Consortium (BloodPAC) is to accelerate the development and validation of liquid biopsy assays that will be introduced into the clinic. To accomplish this goal, the BloodPAC conducts research in the following areas: Data Collection and Analysis within the BloodPAC Data Commons; Preanalytical Variables; Analytical Variables; Patient Context Variables; and Reimbursement. In this document, the BloodPAC’s Analytical Variables Working Group (AV WG) attempts to define a set of generic analytical validation protocols tailored for ctDNA-based Next-Generation Sequencing (NGS) assays. Analytical validation of ctDNA assays poses several unique challenges that primarily arise from the fact that very few tumor-derived DNA molecules may be present in circulation relative to the amount of nontumor-derived cell-free DNA (cfDNA). These challenges include the exquisite level of sensitivity and specificity needed to detect ctDNA, the potential for false negatives in detecting these rare molecules, and the increased reliance on contrived samples to attain sufficient ctDNA for analytical validation. By addressing these unique challenges, the BloodPAC hopes to expedite sponsors’ presubmission discussions with the Food and Drug Administration (FDA) with the protocols presented herein. By sharing best practices with the broader community, this work may also save the time and capacity of FDA reviewers through increased efficiency.
Dual Targeted Therapy: A Possible Option for the Management of Refractory Inflammatory Bowel Disease
Authors: Privitera Giuseppe , Onali Sara , Pugliese Daniela , Renna Sara , Savarino Edoardo , Viola Anna , Ribaldone Davide Giuseppe , Buda Andrea , Bezzio Cristina , Fiorino Gionata , Fantini Massimo Claudio , Scaldaferri Franco , Guidi Luisa , Danese Silvio , Gasbarrini Antonio , Orlando Ambrogio , Armuzzi Alessandro
Published: July 2020

Background and Aims

Dual targeted therapy [DTT] has been proposed as a novel therapeutic strategy for the management of complicated patients with inflammatory bowel diseases [IBD]. Our aim here was to investigate the safety and effectiveness of this approach in a real-life setting.

Methods

We retrospectively extracted data from IBD patients receiving DTT in Italian IBD referral centres. Baseline characteristics, clinical activity of intestinal and extra-intestinal disease, and C-reactive protein levels were recorded. All adverse events were reported. Clinical effectiveness, biochemical remission and safety of DTT were investigated.

Results

Sixteen patients were identified; indications for DTT were: ‘active IBD’ or ‘active EIM’ despite ongoing biological therapy. The most commonly used DTT were: vedolizumab + ustekinumab [three patients] and vedolizumab + adalimumab [three patients]. Clinical response of intestinal or extra-intestinal symptoms, according to the indication for DTT, was reported by all patients by the end of the induction. Four patients discontinued DTT during follow-up. Three patients experienced an adverse event; no serious adverse event was reported.

Conclusions

DTT seems to be an effective and safe treatment and may represent an appealing therapeutic strategy for the management of complicated IBD patients.
Point-of-Care Ultrasound in Inflammatory Bowel Disease
Authors: Allocca Mariangela , Furfaro Federica , Fiorino Gionata , Peyrin-Biroulet Laurent , Danese Silvio
Published: July 2020

Inflammatory bowel diseases [IBD], including Crohn’s disease [CD] and ulcerative colitis [UC], are chronic, relapsing and destructive inflammatory disorders of the gastrointestinal tract which can lead to organ damage and impair quality of life. A ‘treat-to-target’ strategy based on activity and severity of disease and response to treatment with close monitoring of intestinal inflammation is recommended. Ileocolonoscopy [CS] is considered the first-line procedure for the assessment of IBD, and magnetic resonance enterography [MRE] is the current standard for assessing the small bowel and complications in CD, and has been proposed as an alternative procedure to CS in the evaluation of both ileo-colonic CD and UC. As that both CS and MRE are invasive and expensive procedures and unappealing to patients, they are unfeasible as frequent and repetitive tools for the monitoring of disease activity. Bowel ultrasound [US] represents a well-tolerated, non-invasive and cost-effective modality to manage IBD patients in clinical practice. Compared to CS and MRE, bowel US has been shown to have the same level of accuracy in assessing and monitoring disease activity and severity of both CD and UC. It can be performed at the point-of-care and therefore allow for real-time clinical decision-making. Point-of-care ultrasound [POCUS] is suggested as the stethoscope of the future and is gaining interest and diffusion in the medical field because it can be used for the bedside examination of patients. The aim of this review is to discuss point-of-care bowel ultrasound [POCBUS] in the management of patients with IBD.
The impact of coronavirus disease 2019 on the practice of thoracic oncology surgery: a survey of members of the European Society of Thoracic Surgeons (ESTS)
Authors: Depypere Lieven P , Daddi Niccolò , Gooseman Michael R , Batirel Hasan F , Brunelli Alessandro
Published: July 2020

OBJECTIVES

There is widespread acknowledgement that coronavirus disease 2019 (COVID-19) has disrupted surgical services. The European Society of Thoracic Surgeons (ESTS) sent out a survey to assess what impact the COVID-19 pandemic has had on the practice of thoracic oncology surgery.

METHODS

All ESTS members were invited (13–20 April 2020) to complete an online questionnaire of 26 questions, designed by the ESTS learning affairs committee.

RESULTS

The response rate was 23.0% and the completeness rate was 91.2%. The number of treated COVID-positive cases per hospital varied from fewer than 20 cases (30.6%) to more than 200 cases (22.7%) per hospital. Most hospitals (89.1%) postponed surgical procedures. All hospitals performed patient screening with a nasopharyngeal swab, but only 6.7% routinely tested health care workers. A total of 20% of respondents reported that multidisciplinary meetings were completely cancelled and 66%, that multidisciplinary decisions were not different from normal practice. Trends were recognized in prioritizing surgical patients based on age (younger than 70), type of surgery (lobectomy or less), size of tumour (T1–2) and lymph node involvement (N1). Sixty-three percent of respondents reported that surgeons were involved in daily care of COVID-19-positive patients. Fifty-three percent mentioned that full personal protective equipment was available to them when treating a COVID-19-positive patient.

CONCLUSIONS

The COVID-19 pandemic has created issues for the safety of health care workers, and surgeons have been forced to change their routine practice. However, there was no consensus about surgical priorities in lung cancer patients, demonstrating the need for the production of specific guidelines.
Why? – Successful Pseudomonas aeruginosa clones with a focus on clone C
Authors: Lee Changhan , Klockgether Jens , Fischer Sebastian , Trcek Janja , Tümmler Burkhard , Römling Ute
Published: July 2020

The environmental species Pseudomonas aeruginosa thrives in a variety of habitats. Within the epidemic population structure of P. aeruginosa, occassionally highly successful clones that are equally capable to succeed in the environment and the human host arise. Framed by a highly conserved core genome, individual members of successful clones are characterized by a high variability in their accessory genome. The abundance of successful clones might be funded in specific features of the core genome or, although not mutually exclusive, in the variability of the accessory genome. In clone C, one of the most predominant clones, the plasmid pKLC102 and the PACGI-1 genomic island are two ubiquitous accessory genetic elements. The conserved transmissible locus of protein quality control (TLPQC) at the border of PACGI-1 is a unique horizontally transferred compository element, which codes predominantly for stress-related cargo gene products such as involved in protein homeostasis. As a hallmark, most TLPQC xenologues possess a core genome equivalent. With elevated temperature tolerance as a characteristic of clone C strains, the unique P. aeruginosa and clone C specific disaggregase ClpG is a major contributor to tolerance. As other successful clones, such as PA14, do not encode the TLPQC locus, ubiquitous denominators of success, if existing, need to be identified.
Crises of commemoration: Cold War, decolonization and the bungled 1954 D-Day commemoration
Authors: Smith Andrew W M
Published: July 2020

In 1954, international dignitaries and veterans joined the commemoration of the Allied landings on the beaches of Normandy, though not everything went according to plan. For the French organizers, chief among them Gaullist deputy Raymond Triboulet, the event was intended to communicate a unifying, pro-Allied message amid a turbulent political climate. By June 1954, France had recently suffered a decisive defeat at Dien Bien Phu and was politically gripped by the divisive prospect of a European Defence Community. In debates over these crises, war memories surfaced and France’s experience of the Occupation and Liberation enflamed passions. For many who attended the Normandy ceremony in 1954, the missteps of organizers created tension and upset, endangering Allied participation in the Paris Liberation ceremonies to follow. This moment of disjuncture illuminates how currents of memory, international diplomacy, decolonization and broader Cold War tensions all intersected and influenced each other on the Normandy beaches.
Intercohort Variations in the Education–Health Gradient: Sociohistorical Changes in Early-Life Selection Mechanisms in the United States
Authors: Bhatta Tirth R
Published: July 2020

Objectives

Most prior studies on cohort-specific changes in the education gradient relative to health treat the distribution of education within a particular cohort as a “starting place” for understanding later-life health disparities. This premise has obfuscated the role that sociohistorical changes in early-life selection mechanisms play in the widening of education-based inequalities in functional limitations across birth cohorts.

Methods

Drawing from the Health and Retirement Survey (1992–2016; n = 20,920), this study employs inverse probability weight (IPW) to account for early-life selection mechanisms that are likely to affect both educational attainment and functional limitations. IPW-adjusted generalized linear mixed-effects models were used to estimate the total effect of education on functional limitations across birth cohorts (born 1924–1959).

Results

A significant linear decline in the negative effects of childhood socioeconomic disadvantage on education (β = 0.005, p < .01) over the birth year was documented. By contrast, the same variable’s negative effect on functional health increased significantly (β = 0.006, p < .001) across cohorts. Adjustment for childhood socioeconomic status did yield narrower education-based inequalities in functional limitations, but the difference between IPW-adjusted and unadjusted results was not statistically significant. The pattern of significant widening of education-based inequalities (β = −0.05, p < .001) in functional limitations across birth cohorts was maintained.

Discussion

This study underscores the role that sociohistorical changes in early-life selection mechanisms play in modifying patterns of education-based inequalities in health across cohorts.
Positive semidefinite penalty method for quadratically constrained quadratic programming
Authors: Gu Ran , Du Qiang , Yuan Ya-xiang
Published: July 2020

Quadratically constrained quadratic programming (QCQP) appears widely in engineering applications such as wireless communications and networking and multiuser detection with examples like the MAXCUT problem and boolean optimization. A general QCQP problem is NP-hard. We propose a penalty formulation for the QCQP problem based on semidefinite relaxation. Under suitable assumptions we show that the optimal solutions of the penalty problem are the same as those of the original QCQP problem if the penalty parameter is sufficiently large. Then, to solve the penalty problem, we present a proximal point algorithm and an update rule for the penalty parameter. Numerically, we test our algorithm on two well-studied QCQP problems. The results show that our proposed algorithm is very effective in finding high-quality solutions.
Sequential implementation of the EQUIPPED geriatric medication safety program as a learning health system
Authors: Vandenberg Ann E , Kegler Michelle , Hastings S Nicole , Hwang Ula , Wu Daniel , Stevens Melissa B , Clevenger Carolyn , Eucker Stephanie , Genes Nick , Huang Wennie , Ikpe-Ekpo Edidiong , Nassisi Denise , Previll Laura , Rodriguez Sandra , Sanon Martine , Schlientz David , Vigliotti Debbie , Vaughan Camille P
Published: July 2020

Objectives

To present the three-site EQUIPPED academic health system research collaborative, which engaged in sequential implementation of the EQUIPPED medication safety program, as a learning health system; to understand how the organizations worked together to build resources for program scale-up.

Design

Following the Replicating Effective Programs framework, we analyzed content from implementation teams’ focus groups, local and cross-site meeting minutes and sites’ organizational profiles to develop an implementation package.

Setting

Three academic emergency departments that each implemented EQUIPPED over three successive years.

Participants

Implementation team members at each site participating in focus groups (n = 18), local meetings during implementation years, and cross-site meetings during all years of the projects.

Intervention(s)

EQUIPPED provides Emergency Department providers with clinical decision support (education, order sets, and feedback) to reduce prescribing of potentially inappropriate medications to adults aged 65 years and older who received a prescription at time of discharge.

Main Outcome Measure(s)

Implementation process components assembled through successive implementation.

Results

Each site had clinical and environmental characteristics to be addressed in implementing the EQUIPPED program. We identified 10 process elements and describe lessons for each. Lessons guided the compilation of the EQUIPPED intervention package or toolkit, including the EQUIPPED logic model.

Conclusions

Our academic health system research collaborative addressing medication safety through sequential implementation is a learning health system that can serve as a model for other quality improvement projects with multiple sites. The network produced an implementation package that can be vetted, piloted, evaluated, and finalized for large-scale dissemination in community-based settings.