bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Point of Care Ultrasound in Humanitarian Assistance Missions
Authors: Sullivan John F , Polly Matheus , Roman John W , Milder Edmund A , Carter E , Lennon Robert P
Published: January 2021

Introduction

Point of care ultrasound (POCUS) is increasingly used in primary care in the USA and has been shown to provide significant benefit to care in deployed military settings and during disaster relief efforts. It is less studied as a tool during humanitarian assistance missions. We sought to determine the utility of POCUS in a humanitarian assistance setting during the February 2019 joint U.S.–Brazilian hospital assistance mission aboard the Hospitalar Assistance Ship Carlos Chagas along the Madeira River in the Brazilian Amazon.

Materials and Methods

Point of care ultrasound was offered as a diagnostic modality to primary care physicians during the course of a month-long mission. A handheld IVIZ ultrasound machine was loaned for use during this mission by Sonosite. A P21v phased array (5-1 MHz) or an L38v linear (10-5 MHz) transducer was used for scanning. Requests for POCUS examinations, their findings, and changes in patient management were recorded.

Results

Point of care ultrasound examinations were requested and performed in 24 of 814 (3%) outpatient primary care visits. Ten of these studies (42% of POCUS examinations, 1.2% of all patient visits) directed patient management decisions, in each case preventing unnecessary referral.

Conclusions

In this austere setting, POCUS proved to be an inexpensive, effective tool at preventing unnecessary referrals. Future medical humanitarian assistance missions may likewise find POCUS to be a primary care force-multiplier.
Recombinant Human MG53 Protein Protects Against Alkaline-Induced Corneal Injuries in Mice
Authors: Guo Owen , Ju Brent , Shawver McKinley H , Geng Bingchuan , Wei Siqi , Early Terriah , Yi Frank , Tan Tao , Chandler Heather L , Ma Jianjie , Zhu Hua
Published: January 2021

Introduction

The current study was designed to test the potential role of recombinant human MG53 (rhMG53) protein on protecting against alkaline-induced corneal injury in mice.

Materials and Methods

A round filter paper with 2-mm diameter was soaked in 1 mol/L of NaOH solution. The mouse alkaline injury was generated by placing the filter paper directly on the cornea for 30 seconds and washed with 30-mL saline; 10 µL of rhMG53 solution (20 µg/mL) or saline control was topically administrated on the mouse corneas (twice per day for 10 days). Re-epithelialization was measured by fluorescein staining and imaged by a slit lamp equipped with a digital camera. Clinical neovascularization and opacity scores were measured every day after injury. Ten days after injury, mice were sacrificed and corneas were dissected out for flat mount staining of CD31 for neovascularization.

Results

MG53 was present in both dog aqueous humor and human tears. mg53-/- corneas were more susceptible to alkaline-induced corneal injury. Topical treatment of rhMG53 improved re-epithelialization, suppressed neovascularization, and fibrosis induced by alkaline injury.

Conclusions

rhMG53 may be an effective means to treat corneal wounding.
Development and Implementation of the Military Treatment Facility Engagement Committee (MTFEC) to Support Pragmatic Clinical Trials in the Military Health System
Authors: Scarton Dylan V , Roddy William T , Taylor Jerika A , Geda Mary , Brandt Cynthia A , Peduzzi Peter , Kerns Robert D , Pasquina Paul F
Published: January 2021

Introduction

Within the population of military service members and veterans, chronic pain is highly prevalent, often complex, and frequently related to traumatic experiences that are more likely to occur to members of this demographic, such as individuals with traumatic brain injury or limb loss. In September 2017, the National Institutes of Health (NIH), Department of Defense (DOD), and Department of Veterans Affairs (VA) Pain Management Collaboratory (PMC) was formed as a significant and innovative inter-government agency partnership to support a multicomponent research initiative focusing on nonpharmacological approaches for pain management addressing the needs of service members, their dependents, and veterans.

Methods

A Pain Management Collaboratory Coordinating Center (PMC3) was also established to facilitate collective learning across 11 individually funded pragmatic clinical trials (PCTs) designed to optimize the impact of the PMC as an integrated whole. Although the DOD and VA health care systems are ideal sites for the enactment of PCTs, executing these trials within the local context of DOD military treatment facilities (MTFs) can present unique challenges. The Military Treatment Facility Engagement Committee (MTFEC) was created to support the efforts of the PMC3 in its role as a national resource for development and refinement of innovative tools, best practices, and other resources in the conduct of high impact PCTs.

Results

The MTFEC is composed of experts from each service who bring experiences in executing clinical pain management trials that can enhance the planning and execution of the PCTs. It provides expertise and leadership in the execution of research studies at within MTFs and within the DOD health care system, with guidance from PMC3 Directors and in collaboration with NIH, DOD, and VA program and scientific officers.

Discussion/Conclusion

Considering the importance of enacting large-scale, pragmatic studies to implement effective strategies in clinical practice for chronic pain management, the MTFEC has begun to actualize its purpose by identifying potential barriers and challenges to study implementation and exploring how the PMC can support and aid in the execution of PCTs by applying similar approaches to stakeholder and subject matter engagement for their research.
Localization of Arterial Bleeds Using Pulse Wave Reflections
Authors: Venugopal Prem , Marinelli Luca
Published: January 2021

Introduction

Localization of internal arterial bleeds is necessary for treatment in the battlefield. In this article, we describe a novel approach that utilizes pulse wave reflections generated by a bleed to locate it.

Materials and Methods

To demonstrate our approach, velocity and diameter waveforms in the presence of bleeds were simulated using the 1D wave propagation equations in a straight-vessel model of the human thoracic aorta. The simulated waveforms were then decomposed into forward and backward components using wave intensity analysis. Reflections arising from the bleed were identified from the decomposed waveforms.

Results

Reflection generated by the bleed introduced a new feature in the backward component, compared to the normal, no-bleed condition. The bleed location could be determined from the time delay between this reflection feature and the forward wave creating it, and the pulse wave velocity in the vessel.

Conclusions

The findings of this study could be utilized by ultrasound for hemorrhage localization.
Demographic Variation in Military Life Stress and Perceived Support Among Military Spouses
Authors: Corry Nida H , Williams Christianna S , Radakrishnan Sharmini , McMaster Hope S , Sparks Alicia C , Briggs-King Ernestine , Karon Samantha S , Stander Valerie A
Published: January 2021

Introduction

Military spouses play a critical role in supporting military service members, and thus, their experiences may have a significant impact on the well-being, readiness, and resilience of the U.S. Armed Forces. Research suggests that military spouses experience unique stressors as a result of military life, but few studies have assessed demographic factors associated with their experiences of military life and perceived support.

Materials and Methods

Using data from the Millennium Cohort Family Study, a nationwide survey of 9,872 married spouses of service members with 2 to 5 years of military service, this study examined differences in experiences of military life and perceived support across multiple understudied subgroups of military spouses. Key outcomes included military-related stressors (e.g., deployment-related experiences), perceived social support, and perceived military efforts to provide support.

Results

Military life stress and perceived support differed across military spouse, service member, and family characteristics. Results indicated that spouses who are older than age 35 or are married to enlisted service members in the Army, Navy, or Marines are more likely to experience heightened military stress or less perceived social support. Dual-military couples reported experiencing less stress associated with military life and perceiving more social support and support from the military, compared with spouses who have never served in the military.

Conclusion

These findings may help guide effective channeling of resources and outreach to potentially vulnerable military families.
Lower Neck Injury Assessment Risk Curves Based on Matched-Pair Human Data for Anthropomorphic Test Devices
Authors: Humm John , Yoganandan Narayan
Published: January 2021

Introduction

Under G +x accelerative loading, the Hybrid III anthropomorphic test device (ATD) is used to advance human safety. Although injury assessment risk curves (IARCs) are available at the level of the occipital condyles (commonly termed as upper neck), they do not exist for the cervical-thoracic junction (lower neck). The objectives of this study are to develop IARCs under G +x impact accelerations for the Hybrid III ATD and test device for human occupant restraint (THOR) ATD at the cervical thoracic junction.

Methods

A series of Hybrid III ATD tests were conducted using input conditions that matched previously published cadaver tests. A separate series of THOR-ATD tests were conducted using the same input conditions that matched the same previously published cadaver tests. This type of experimental design where the cadaver input condition is the same as the ATD tests are termed matched-pair tests (Cadaver-Hybrid III and Cadaver-THOR-ATD). Injury outcomes from human cadaver tests were used with loads at the cervical thoracic junction, measured in the ATD tests. Data were censored based on injury outcomes and the number of tests conducted on each specimen. Parametric survival analysis was used to derive IARCs for cervical thoracic junction force-, moment-, and interaction-based lower neck injury criterion (LNic).

Results

Injuries were scored according to the Abbreviated Injury Scale scheme. Abbreviated Injury Scale 1 or 2 was scored as injured. The 50% risk levels for the Hybrid III ATD were 315 N, 70 Nm, and 1.12 for the cervical thoracic A/P shear force-, sagittal plane extension moment-, and LNic-based injury criterion, respectively. Results for the THOR ATD were 261 N, 69 Nm, and 1.51.

Conclusions

This is the first study to develop cervical thoracic junction IARCs for the ATDs based on force, moment, and LNic for posterior to anterior loading.
Approaches for Monitoring Warfighter Blast-related Exposures in Training to Develop Effective Safety Standards
Authors: Kornguth Steven , Rylander Henry G , Smith Spencer , Campbell Julia , Steffensen Steve , Arnold David , Athey Alex , Rutledge J Neal
Published: January 2021

Introduction

Traumatic brain injuries are of concern to the sports and military communities because of the age of the participants and costly burden to society. To markedly reduce the impact of traumatic brain injury and its sequela (TBI-S), it is necessary to determine the initial vulnerability of individuals as well as identify new technologies that indicate early signs of TBI-S.

Materials and Methods

Currently, diverse methods have been used by the authors and others in laboratory settings to reveal early signs of persistent TBI-S including simulation modeling of the effect of rapid deceleration on the deviatoric strain (shear force) imposed on specific brain regions, auditory evoked potential (AEP) measurements to determine injury to the auditory cortex optokinetic nystagmus (OKN) measures sensitive to vestibular trauma, and optical coherence tomography (OCT) measures that reveal changes in central visual function obtained noninvasively by examination of the retina.

Results

Simulation studies provided technical information on maximal deviatoric strain at the base of the sulci and interface of gray and white matter consistent with results from neuropathology and from magnetic resonance imaging. The AEP and OKN reveal measurable injury to similar regions below the Sylvian fissure including auditory cortex and midbrain, and the OCT reveals changes to the retina consistent with forceful deceleration effects.

Conclusions

The studies and results are consistent with prior work demonstrating that noninvasive tests may be sensitive to the presence of TBI-S, potentially in the training field as advances in the portability of test instruments are underway. When combined with baseline data gathered from individuals in quantitative form, key variances can emerge. Therefore, it is hypothesized that AEP, OKN, and OCT, taken together, may yield faster objective and quantitative neurophysiological measures serving as a “signature” of neural injury and more indicative of potentially persistent TBI-S—recommending larger scale longitudinal studies.
Upright Magnetic Resonance Imaging Study of Cervical Flexor/Extensor Musculature and Cervical Lordosis in Females After Helmet Wear
Authors: Choi Hoon , Varghese Vicky , Baisden Jamie , Braza Diane W , Banerjee Anjishnu , Yoganandan Narayan
Published: January 2021

Introduction

Addition of head-supported mass imparts greater demand on the human neck to maintain functionality. The same head-supported mass induces greater demand on the female spine than the male spine because female necks are comparatively slender. Prevalence of neck pain is greater in military than civilian population because of the head-borne mass (among other factors). The goal of this study is to determine quantifiable parameters related to muscle geometry using female human volunteers and upright magnetic resonance imaging.

Materials and Methods

Young healthy subjects were consented. Demographics and head–neck anthropometry were recorded. For all the 7 subjects, the T1- and T2-weighted magnetic resonance imaging in the neutral sitting position was obtained immediately following donning and after 4 hours of continuous wear of standard issued military helmet, while seated in the same posture for 4 hours. Cross-sectional areas of sternocleidomastoid and multifidus muscles from C2-C7, overall and segmental Cobb angles (C2-T1), and centroid and radius of each muscle were calculated. Data were compared with determine differences with the continuous helmet wear.

Results

There were level specific changes in morphological parameters for each of the muscles. Significant difference (P < 0.05) in cross-sectional areas was noted at C2-3 level for sternocleidomastoid and at C3-4 and C5-6 levels for multifidus. For centroid angles, significant difference (P < 0.05) was observed at C2-3 and C5-6 levels for sternocleidomastoid and at C3-4 level for multifidus. There was no significant difference (P > 0.05) in muscle centroid radii between the pre- and posttest conditions.

Conclusions

Alterations in muscle geometries were muscle specific and level specific: sternocleidomastoid was significant at the upper level, whereas multifidus was significant at the mid-lower cervical spine segments. The insignificant difference in the Cobb angles was attributed to length of time of continuous helmet wear attributed and sample size. Helmet wear can lead to morphometric alterations in cervical flexor/extensor musculature in females.
Medical Challenges in Underground Warfare
Authors: Sorkin Alex , Nadler Roy , Sommer Adir , Tsur Avishai M , Chen Jacob , Bader Tarif , Benov Avi
Published: January 2021

Introduction

Throughout history, underground systems have served military purposes in both offensive and defensive tactical settings. With the advance of underground mining, combat tactics, and weapon systems, providing medical support in the subterranean battlefield is a constantly growing challenge. This retrospective cohort study describes the Israeli Defense Force (IDF) Medical Corps experience with treating casualties from underground warfare, as recorded in the IDF Trauma Registry.

Methods

A retrospective cohort study of all casualties engaged in underground warfare, between the years 2004-2018. Medical data were extracted from the IDF Trauma Registry and tactical data were obtained from operational reports. An expert committee characterized the most prevalent challenges. Recommendations were based on a literature review and the lessons learned by the IDF experience.

Results

During the study period, 26 casualties were injured in the underground terrain. Of casualties, 12 (46%) due to blast injuries, 9 (35%) were due to smoke inhalation, and 5 (19%) due to crushing injuries. All were males, and the average age was 21.6 years. Ten (38%) were killed in action (died before reaching a medical facility). All 16 casualties reaching the hospital survived (Table I). The expert committee divided the most common challenges into three categories—tactical, environmental, and medical. An overview of medical response planning, common injuries, and designated combat casualty care are discussed below. As in all combat casualty care, the focus should be on safety, bleeding control, and rapid evacuation.

Conclusion

To plan and provide medical support, a thorough understanding of operational planning is essential. This manuscript presents the evolution of underground warfare, tactical and medical implications, environmental hazards, and common casualty care challenges.
Loading Effect of Prosthetic Feet’s Anthropomorphicity on Transtibial Osseointegrated Implant
Authors: Pitkin Mark , Frossard Laurent
Published: January 2021

Introduction

Osseointegrated implants for direct skeletal attachment of transtibial prosthesis carry risks that are yet to be fully resolved, such as early loosening, mechanical failure of percutaneous and medullar parts of implant, periprosthetic issues, and infections. Underloading could lead to early loosening and infection. Overloading might compromise the bone–implant interface. Therefore, Goldilocks loading regimen applied by transtibial bone-anchored prostheses is critical for safe and efficient development of osseointegration around the implant during rehabilitation and beyond. We hypothesized that Goldilocks loading could be achieved when ambulating with a so-called anthropomorphic prosthetic ankle showing moment–angle relationship similar to a sound ankle.

Materials and Methods

Quantitative characteristics of the moment–angle curve of the sound ankle during dorsiflexion phase of a free-pace walking were extracted for 4 able-bodied participants (experiment 1). A slope of the moment–angle curve (stiffness) was calculated twice: for the first half and for the second half of the moment–angle curve. The difference of stiffnesses (those at the second half minus at the first half) was called the index of anthropomorphicity (IA). By definition, positive IA is associated with concave shape of the moment–angle curve, and the negative IA is associated with convex shape. In experiment 2, the same recordings and calculations were performed for 3 participants fitted with transtibial osseointegrated fixation during walking with their usual feet and the Free-Flow Foot (Ohio Willow Wood). The Free-Flow Foot was selected for its anthropomorphicity demonstrated in the previous studies with amputees using traditional socket attachment.

Results

The IA was 5.88 ± 0.93 for the able-bodied participants, indicating that the stiffness during the first part of the dorsiflexion phase was substantially fewer than during the second parts, as the calf muscles resisted to angulation in ankle substantially less than during the second part of dorsiflexion phase. For amputees fitted with Free-Flow Foot, IA was 2.68 ± 1.09 and −2.97 ± 2.37 for the same amputees fitted with their usual feet.

Conclusions

Indexes of anthropomorphicity, while of different magnitude, were positive in control able-bodied group and in the amputee group wearing Free-Flow Foot, which was qualitatively associated with concave shape of their moment–angle curves. The 3 usual feet worn by the participants were classified as nonanthropomorphic as their individual moment–angle curves were convex and the corresponding IAs were negative. Furthermore, this study showed that a foot with anthropomorphic characteristics tends to decrease maximal loads at the bone–implant interface as compared to the nonanthropomorphic feet and possibly may minimize the risks to compromise the integrity of this interface.
Paper-Based Microfluidic Devices: Low-Cost Platforms for Rapid Biochemical Detection
Authors: Ünal Bariş , Camci-Unal Gulden , Mahmud Ken
Published: January 2021

Introduction

We developed low-cost, portable paper-based diagnostic devices for detection of human immunoglobulin M (IgM) and immunoglobulin G (IgG) in serum without any sample preparation. These devices can be used to help identify presence of diseases, used to provide rapid results (<5 minutes), readily used by untrained personnel, employed in austere environments, configured to obtain multiplexed assays, and easily disposed of.

Materials and Methods

We successfully accomplished colorimetric detection of human IgG and human IgM using a sandwich-style assay within the microfluidic paper device via vertical flow immunoassay configuration. The reaction zone in the wax printed paper layer is a small circular pattern. Gold nanoparticles conjugated with anti-human IgG and IgM antibodies have been used for colorimetric detection of IgG or IgM by naked eye. Colorimetric signal can be precisely quantified through implementation of image analysis software which can be developed as an app for a smartphone. The size of the device is 2 cm × 2 cm × 1 mm.

Results

Colorimetric detection of human IgG was accomplished at 100 fg/mL concentration using a gold nanoparticle–conjugated anti-human IgG antibody. The developed platform has a dynamic range of IgM and IgG concentrations between 0.1 pg/mL and 100 μg/mL. These devices provided a color readout in <5 minutes using 20 µL of serum. We also demonstrated that the devices show a significant degree of ruggedness and temperature stability as they were able to provide satisfactory results (detection of 0.1 pg/mL IgG) after 14 days of long stability and shelf-life experiment at an elevated temperature of at least 50 ˚C—the shelf life can be as long as 180 days under ambient conditions for detection of 100 µg/mL IgG.

Conclusions

Because of the inherent simplicity of the device operation and their ease of use, there is no variation between samples and users of the device. This low-cost approach enables multiplexing with >1 measurement performed in parallel at the same time. We anticipate that because of the sensitivity, specificity, ease of use, and overall reliability, this approach will become a standard for diagnosis of diseases and health conditions.
Mitigating the effects of undersampling in weak lensing shear estimation with metacalibration
Authors: Kannawadi Arun , Rosenberg Erik , Hoekstra Henk
Published: January 2021

metacalibration is a state-of-the-art technique for measuring weak gravitational lensing shear from well-sampled galaxy images. We investigate the accuracy of shear measured with metacalibration from fitting elliptical Gaussians to undersampled galaxy images. In this case, metacalibration introduces aliasing effects leading to an ensemble multiplicative shear bias about 0.01 for Euclid  and even larger for the Roman Space Telescope, well exceeding the missions’ requirements. We find that this aliasing bias can be mitigated by computing shapes from weighted moments with wider Gaussians as weight functions, thereby trading bias for a slight increase in variance of the measurements. We show that this approach is robust to the point-spread function in consideration and meets the stringent requirements of Euclid for galaxies with moderate to high signal-to-noise ratios. We therefore advocate metacalibration as a viable shear measurement option for weak lensing from upcoming space missions.
The radiative efficiency of neutron stars at low-level accretion
Authors: Qiao Erlin , Liu B F
Published: January 2021

When neutron star low-mass X-ray binaries (NS-LMXBs) are in the low-level accretion regime (i.e. $L_{\rm X}\lesssim 10^{36}\ \rm erg\ s^{-1}$), the accretion flow in the inner region around the NS is expected to exist in the form of the hot accretion flow, e.g. the advection-dominated accretion flow (ADAF) as that in black hole X-ray binaries. Following our previous studies in Qiao & Liu (2020a, b) on the ADAF accretion around NSs, in this paper, we investigate the radiative efficiency of NSs with an ADAF accretion in detail, showing that the radiative efficiency of NSs with an ADAF accretion is much lower than that of $\epsilon \sim {\dot{M} GM\over R_{*}}/{\dot{M} c^2}\sim 0.2$ despite the existence of the hard surface. As a result, given an X-ray luminosity LX (e.g. between 0.5 and 10 keV), $\dot{M}$ calculated by $\dot{M}=L_{\rm X}{R_{*}\over {GM}}$ is lower than the real $\dot{M}$ calculated within the framework of the ADAF accretion. The real $\dot{M}$ can be more than two orders of magnitude higher than that calculated by $\dot{M}=L_{\rm X}{R_{*}\over {GM}}$ with appropriate model parameters. Finally, we discuss that if applicable, the model of ADAF accretion around a NS can be applied to explain the observed millisecond X-ray pulsation in some NS-LMXBs (such as PSR J1023+0038, XSS J12270−4859, and IGR J17379−3747) at a lower X-ray luminosity of a few times of $10^{33}\ \rm erg\ s^{-1}$, since at this X-ray luminosity the calculated $\dot{M}$ with the model of ADAF accretion can be high enough to drive a fraction of the matter in the accretion flow to be channelled on to the surface of the NS forming the X-ray pulsation.
Explosive nucleosynthesis of a metal-deficient star as the source of a distinct odd-even effect in the solar twin HIP 11915
Authors: Yana Galarza Jhon , Meléndez Jorge , Karakas Amanda I , Asplund Martin , Lorenzo-Oliveira Diego
Published: January 2021

The abundance patterns observed in the Sun and in metal-poor stars show a clear odd-even effect. An important question is whether the odd-even effect in solar-metallicity stars is similar to the Sun, or if there are variations that can tell us about different chemical enrichment histories. In this work, we report for the first time observational evidence of a differential odd-even effect in the solar twin HIP 11915, relative to the solar odd-even abundance pattern. The spectra of this star were obtained with high-resolving power (140 000) and signal-to-noise ratio (∼420) using the ESPRESSO spectrograph and the VLT telescope. Thanks to the high spectral quality, we obtained extremely precise stellar parameters (σ(Teff) = 2 K, $\sigma (\rm {[Fe/H]})$ = 0.003 dex, and σ(log g) = 0.008 dex). We determine the chemical abundance of 20 elements (Z ≤ 39) with high precision (∼0.01 dex), which shows a strong pattern of the odd-even effect even after performing galactic chemical evolution corrections. The odd-even effect is reasonably well-reproduced by a core-collapse supernova of 13 $\rm {M_{\odot }}$ and metallicity Z = 0.001 diluted into a metal-poor gas of 1 $\rm {M_{\odot }}$. Our results indicate that HIP 11915 has an odd-even effect slightly different than the Sun, thus confirming a different supernova enrichment history.
In vitro selected GUAA tetraloop-binding receptors with structural plasticity and evolvability towards natural RNA structural modules
Authors: Zakrevsky Paul , Calkins Erin , Kao Yi-Ling , Singh Gurkeerat , Keleshian Vasken L , Baudrey Stephanie , Jaeger Luc
Published: January 2021

GNRA tetraloop-binding receptor interactions are key components in the macromolecular assembly of a variety of functional RNAs. In nature, there is an apparent bias for GAAA/11nt receptor and GYRA/helix interactions, with the former interaction being thermodynamically more stable than the latter. While past in vitro selections allowed isolation of novel GGAA and GUGA receptors, we report herein an in vitro selection that revealed several novel classes of specific GUAA receptors with binding affinities comparable to those from natural GAAA/11nt interactions. These GUAA receptors have structural homology with double-locked bulge RNA modules naturally occurring in ribosomal RNAs. They display mutational robustness that enables exploration of the sequence/phenotypic space associated to GNRA/receptor interactions through epistasis. Their thermodynamic self-assembly fitness landscape is characterized by a rugged neutral network with possible evolutionary trajectories toward natural GNRA/receptor interactions. High throughput sequencing analysis revealed synergetic mutations located away from the tertiary interactions that positively contribute to assembly fitness. Our study suggests that the repertoire of GNRA/receptor interactions is much larger than initially thought from the analysis of natural stable RNA molecules and also provides clues for their evolution towards natural GNRA/receptors.
A chronic high phosphate intake in mice is detrimental for bone health without major renal alterations
Authors: Ugrica Marko , Bettoni Carla , Bourgeois Soline , Daryadel Arezoo , Pastor-Arroyo Eva-Maria , Gehring Nicole , Hernando Nati , Wagner Carsten A , Rubio-Aliaga Isabel
Published: January 2021

Background

Phosphate intake has increased in the last decades due to a higher consumption of processed foods. This higher intake is detrimental for patients with chronic kidney disease, increasing mortality and cardiovascular disease risk and accelerating kidney dysfunction. Whether a chronic high phosphate diet is also detrimental for the healthy population is still under debate.

Methods

We fed healthy mature adult mice over a period of 1 year with either a high (1.2% w/w) or a standard (0.6% w/w) phosphate diet, and investigated the impact of a high phosphate diet on mineral homeostasis, kidney function and bone health.

Results

The high phosphate diet increased plasma phosphate, parathyroid hormone (PTH) and calcitriol levels, with no change in fibroblast growth factor 23 levels. Urinary phosphate, calcium and ammonium excretion were increased. Measured glomerular filtration rate was apparently unaffected, while blood urea was lower and urea clearance was higher in animals fed the high phosphate diet. No change was observed in plasma creatinine levels. Blood and urinary pH were more acidic paralleled by higher bone resorption observed in animals fed a high phosphate diet. Total and cortical bone mineral density was lower in animals fed a high phosphate diet and this effect is independent of the higher PTH levels observed.

Conclusions

A chronic high phosphate intake did not cause major renal alterations, but affected negatively bone health, increasing bone resorption and decreasing bone mineral density.
The podocyte as a direct target of glucocorticoids in nephrotic syndrome
Authors: Broek Martijn van den , Smeets Bart , Schreuder Michiel F , Jansen Jitske
Published: January 2021

Nephrotic syndrome (NS) is characterized by massive proteinuria; podocyte loss or altered function is a central event in its pathophysiology. Treatment with glucocorticoids is the mainstay of therapy, however, many patients experience one or multiple relapses and prolonged use may be associated with severe adverse effects. Recently the beneficial effects of glucocorticoids have been attributed to a direct effect on podocytes in addition to the well-known immunosuppressive effects. The molecular effects of glucocorticoid action have been studied using animal and cell models of NS. This review provides a comprehensive overview of different molecular mediators regulated by glucocorticoids, including an overview of the model systems that were used to study them. Glucocorticoids are described to stimulate podocyte recovery by restoring pro-survival signalling of slit diaphragm–related proteins and limiting inflammatory responses. Of special interest is the effect of glucocorticoids on stabilizing the cytoskeleton of podocytes, since these effects are also described for other therapeutic agents used in NS, such as cyclosporin. Current models provide much insight but do not fully recapitulate the human condition since the pathophysiology underlying NS is poorly understood. New and promising models include the glomerulus-on-a-chip and kidney organoids, which have the potential to be further developed into functional NS models in the future.
Effectiveness of Varenicline Versus Combination Nicotine Replacement Therapy for Smoking Cessation: One-Year Outcomes in a Smoking Cessation Clinic in Taiwan
Authors: Hsueh Kuang-Chieh , Tang Pei-Ling , McRobbie Hayden
Published: January 2021

Introduction

Varenicline and combination nicotine replacement treatment (cNRT) have been recommended as the most effective pharmacotherapies, with equal abstinence rate for smoking cessation in a network meta-analysis of randomized trials, but data from real-world long-term follow-up studies are rare. This study aimed to compare the 12-month sustained abstinence rates of smokers using varenicline versus cNRT in their quit attempt.

Methods

A total of 3569 smokers were recruited via the Department of Family Medicine outpatient department at Kaohsiung Veteran General Hospital between June 2013 and March 2019. Participants received counseling from a physician and chose either varenicline (N = 2870) or cNRT (N = 699) for smoking cessation. Both varenicline and cNRT users could receive a free 8-week supply and eight clinic visits over 90 days. Participants were followed-up by telephone at 12, 24, and 52 weeks from first visit. The primary outcome measure of the study was self-reported sustained abstinence up to 52 weeks.

Results

Varenicline users had a significantly higher sustained abstinence rate at weeks 12–52, adjusted for baseline variables (15.2% vs 10.3%, p = .001; adjusted odds ratio = 1.47, 95% confidence interval: 1.05–2.05). Other significant predictors of 52 weeks sustained abstinence were being male, having a higher income, attending more clinical visits, and have lower nicotine dependence.

Conclusion

Varenicline appears to have higher sustained abstinence rates to 52 weeks compared with cNRT, in a smoking cessation clinic where smokers can choose their medication option.

Implications

Network meta-analysis of randomized trials suggests that varenicline and cNRT are similarly effective for smoking cessation. This study shows that 1-year sustained abstinence rates were significantly higher among smokers using varenicline, compared with smokers using cNRT, when used as part of a structured smoking cessation program. These findings are highly relevant to policy makers and service providers to help determine provision of smoking cessation treatment.
Guns for Votes: Wedge Politics in the Canadian Multiparty System
Authors: Dumouchel David , Ouellet Catherine , Giasson Thierry
Published: January 2021

This article contributes to the emerging literature on wedge issues and on electoral strategies in multiparty electoral systems by studying the implementation and effectiveness of a concerted electoral communication strategy deployed by the Conservative party of Canada around the elimination of the gun registry, in the late 2000s. First, using a quantitative content analysis of the Parliamentary debates from 2006 to 2011, it reveals how the Conservatives exploited the issue in order to create divisions amongst opposing opposition MPs and amongst targeted segments of partisan voters of other national parties. Secondly, using georeferenced pool data from Vote Compass, it finds empirical evidence that the Conservatives’ efforts won them new support in the 2011 federal elections, especially amongst cross-pressured voters and within the ridings that were targeted during the debates. In doing so, the article provides a rare empirical example of wedge politics carried in a multiparty system.
What Factors Influence Clinicians’ Use of Technology in Neurorehabilitation? A Multisite Qualitative Study
Authors: Bower Kelly J , Verdonck Michele , Hamilton Anita , Williams Gavin , Tan Dawn , Clark Ross A
Published: January 2021

Objective

Technology is being increasingly used for physical assessment and interventions in health care settings. However, clinical adoption is relatively slow, and the factors affecting use remain underexplored. This study aimed to investigate factors influencing technology use by clinicians working in neurorehabilitation.

Methods

In this qualitative study, 9 physical therapists and 9 occupational therapists (N = 18) were recruited from urban and regional locations in Australia and in Singapore. Three 60-minute focus groups were conducted via video conferencing. Each group comprised 3 physical therapists and 3 occupational therapists working across different neurorehabilitation settings. Participants were asked to discuss which technologies they used in their workplace for physical assessment and treatment and barriers, motivators, and future desires for technology use. Transcripts were analyzed independently using an inductive approach to generate codes and themes.

Results

Our results comprised 3 themes and 7 categories. These were encompassed by a single overarching theme, namely “Technology use is influenced by the benefits and challenges of the technology itself, users, and organizational context.” Themes showed that technology should promote effective interventions, is preferred if easy to use, and should be dependable. Furthermore, clinical reasoning is important, and users have varying levels of receptivity and confidence in technology use. Also, organizational resources are required, along with supportive cultures and processes, to facilitate technology use.

Conclusions

The themes identified multiple and interlinking factors influencing clinicians’ use of technology in neurorehabilitation settings. Clinicians often consider context-specific benefits and challenges when deciding whether to use technology. Although our study found that clinicians generally perceived technology as having a beneficial role in improving health outcomes, there were several challenges raised. Therefore, the characteristics of the technology itself, individual users, and organizational context should be considered.

Impact

These findings will guide successful technology implementation and future developments.
Time Window for Ischemic Stroke First Mobilization Effectiveness: Protocol for an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial
Authors: Zheng Yu , Yan Chengjie , Shi Haibin , Niu Qi , Liu Qianghui , Lu Shanshan , Zhang Xintong , Cheng Yihui , Teng Meiling , Wang Lu , Zhang Xiu , Hu Xiaorong , Li Jian , Lu Xiao , Reinhardt Jan D ,   TIME Trial Collaboration Group
Published: January 2021

Objective

The purpose of this study is to investigate the optimal time window for initiating mobilizing after acute ischemic stroke.

Methods

The TIME Trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in which mobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs.

Impact

The TIME Trial is designed to answer the question “when is the best time to start mobilization after stroke?” The effect of timing is isolated from the effect of type and dose of mobilization by otherwise applying a standard mobilization protocol across groups. The TIME Trial may, therefore, contribute to increasing the knowledge base regarding the optimal time window for initiating mobilization after acute ischemic stroke.
The Maximum Entropy of a Metric Space
Authors: Leinster Tom , Roff Emily
Published: January 2021

We define a one-parameter family of entropies, each assigning a real number to any probability measure on a compact metric space (or, more generally, a compact Hausdorff space with a notion of similarity between points). These generalize the Shannon and Rényi entropies of information theory. We prove that on any space X, there is a single probability measure maximizing all these entropies simultaneously. Moreover, all the entropies have the same maximum value: the maximum entropy of X. As X is scaled up, the maximum entropy grows, and its asymptotics determine geometric information about X, including the volume and dimension. And the large-scale limit of the maximizing measure itself provides an answer to the question: what is the canonical measure on a metric space? Primarily, we work not with entropy itself but its exponential, which in its finite form is already in use as a measure of biodiversity. Our main theorem was first proved in the finite case by Leinster and Meckes.
Multivariate spatial feature selection in fMRI
Authors: Jolly E , Chang L J
Published: January 2021

Multivariate neuroimaging analyses constitute a powerful class of techniques to identify psychological representations. However, not all psychological processes are represented at the same spatial scale throughout the brain. This heterogeneity is apparent when comparing hierarchically organized local representations of perceptual processes to flexible transmodal representations of more abstract cognitive processes such as social and affective operations. An open question is how the spatial scale of analytic approaches interacts with the spatial scale of the representations under investigation. In this article, we describe how multivariate analyses can be viewed as existing on a spatial spectrum, anchored by searchlights used to identify locally distributed patterns of information on one end, whole brain approach used to identify diffuse neural representations at the other and region-based approaches in between. We describe how these distinctions are an important and often overlooked analytic consideration and provide heuristics to compare these different techniques to choose based on the analyst’s inferential goals.
Simvastatin Augmentation for Patients With Early-Phase Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Placebo-Controlled Trial
Authors: Sommer Iris E , Gangadin Shiral S , de Witte Lot D , Koops Sanne , van Baal C , Bahn Sabine , Drexhage Hemmo , van Haren N E M , Veling Wim , Bruggeman R , Martens Peter , Wiersma Sybren , Veerman Selene R T , Grootens Koen P , van Beveren Nico , Kahn Rene S , Begemann Marieke J H
Published: January 2021

Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain barrier, has anti- inflammatory and neuroprotective effects and reduces metabolic syndrome. In this study, we investigated if 12 months of simvastatin augmentation can improve symptoms and cognition in patients with early SSD. This double-blind placebo-controlled trial included 127 SSD patients across the Netherlands, <3 years after their diagnosis. From these, 119 were randomly assigned 1:1 to simvastatin 40 mg (n = 61) or placebo (n = 58), stratified for sex and study site. Primary outcomes were symptom severity and cognition after 12 months of treatment. Depression, symptom subscores, general functioning, metabolic syndrome, movement disorders, and safety were secondary outcomes. Intention to treat analyses were performed using linear mixed models and ANCOVA. No main effect of simvastatin treatment was found on total symptom severity after 12 months of treatment as compared to placebo (X2(1) = 0.01, P = .90). Group differences varied over time (treatment*time X2(4) = 11.2; P = .025), with significantly lower symptom severity in the simvastatin group after 6 months (mean difference = −4.8; P = .021; 95% CI: −8.8 to −0.7) and at 24 months follow-up (mean difference = −4.7; P = .040; 95% CI: −9.3 to −0.2). No main treatment effect was found for cognition (F(1,0.1) = 0.37, P = .55) or secondary outcomes. SAEs occurred more frequently with placebo (19%) than with simvastatin (6.6%). This negative finding corroborates other large scale studies on aspirin, minocycline, and celecoxib that could not replicate positive findings of smaller studies, and suggests that anti-inflammatory augmentation does not improve the clinical presentation of SSD.
Biomarker Profiles in Psychosis Risk Groups Within Unaffected Relatives Based on Familiality and Age
Authors: Türközer Halide Bilge , Ivleva Elena I , Palka Jayme , Clementz Brett A , Shafee Rebecca , Pearlson Godfrey D , Sweeney John A , Keshavan Matcheri S , Gershon Elliot S , Tamminga Carol A
Published: January 2021

Investigating biomarkers in unaffected relatives (UR) of individuals with psychotic disorders has already proven productive in research on psychosis neurobiology. However, there is considerable heterogeneity among UR based on features linked to psychosis vulnerability. Here, using the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset, we examined cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands, stratified by 2 widely used risk factors: familiality status of the respective proband (the presence or absence of a first- or second-degree relative with a history of psychotic disorder) and age (within or older than the common age range for developing psychosis). We investigated biomarkers that best differentiate the above specific risk subgroups. Additionally, we examined the relationship of biomarkers with Polygenic Risk Scores for Schizophrenia (PRSSCZ) in a subsample of Caucasian probands and healthy controls (HC). Our results demonstrate that the Brief Assessment of Cognition in Schizophrenia (BACS) score, antisaccade error (ASE) factor, and stop-signal task (SST) factor best differentiate UR (n = 169) from HC (n = 137) (P = .013). Biomarker profiles of UR of familial (n = 82) and non-familial (n = 83) probands were not significantly different. Furthermore, ASE and SST factors best differentiated younger UR (age ≤ 30) (n = 59) from older UR (n = 110) and HC from both age groups (age ≤ 30 years, n=49; age > 30 years, n = 88) (P < .001). In addition, BACS (r = −0.175, P = .006) and ASE factor (r = 0.188, P = .006) showed associations with PRSSCZ. Taken together, our findings indicate that cognitive biomarkers—“top-down inhibition” impairments in particular—may be of critical importance as indicators of psychosis vulnerability.