bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol for a prospective randomised double-blind placebo-controlled clinical trial investigating a Better Outcome with Melatonin compared to Placebo Administered to normalize sleep–wake cycle and treat hypoactive ICU Delirium: the Basel BOMP-AID study
Authors: Hollinger Alexa , von Felten Stefanie , Sutter Raoul , Huber Jan , Tran Fabian , Reinhold Simona , Abdelhamid Salim , Todorov Atanas , Gebhard Caroline Eva , Cajochen Christian , Steiner Luzius A , Siegemund Martin
Published: April 2020

Introduction

Delirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (BetterOutcome withMelatonin compared toPlaceboAdministered to normalize sleep-wake cycle and treat hypoactiveICUDelirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium.

Methods and analysis

The Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach.

Ethics and dissemination

This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use; Good Clinical Practice (GCP) or ISO EN 14155 (as far as applicable), as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal.

Trial registration number

NCT03438526.

Protocol version

Clinical Study Protocol Version 3, 10.03.2019.
How do community advisory boards fulfil their ethical role in HIV clinical trials? A protocol for a systematic review of qualitative evidence
Authors: Pancras Godwin , Amour Maryam , Mwakyandile Tosi , Morris Baraka , Sunguya Bruno F , Mmbaga Blandina
Published: April 2020

Introduction

Community advisory boards (CABs) continue to gain wide use and acceptance in global health research including in HIV clinical trials. They provide means through which community concerns regarding the trial can be considered by the research team, and provide an important platform of communication between the researchers and the community about study goals. Therefore, this systematic review protocol will guide the review of qualitative evidence on the ethical roles of CABs in HIV clinical trials based on the three fundamental ethical principles: respect for the person, beneficence and justice.

Methods and analysis

This systematic review of qualitative evidence will involve searching four medical databases: PubMed, ScienceDirect, CINAHL and Cochrane Library. Additionally, other relevant evidence will be obtained through hand searching and grey literature. Searches will be limited to studies published in the English language from 1989 (the year that CABs were first established in HIV clinical trials) to 2019. Articles searched will be screened by two independent authors based on inclusion and exclusion criteria. Included articles will be appraised for quality using the Critical Appraisal Skills Programme checklist and followed by qualitative data extraction. Findings will be analysed based on the meta-aggregative approach with the aid of EPPI-Reviewer 4 web-based software.

Ethics and dissemination

Ethical approval does not apply to this review. Data will be disseminated through scientific conferences and peer-reviewed journals to inform policies and stake-holders about the ethical role of CABs.

PROSPERO registration number

CRD42019133787.
Implementing the patient care collaborative model in three general internal medicine units: a mixed-methods healthcare improvement initiative
Authors: LoPresti Kelly , Camera Julianne , Barrett Elizabeth , Gosse Caroline , Johnson Donna , Amirthavasar Gaya , Nashid John , Mbuagbaw Mirabel , Vanniyasingam Thuvaraha , Mbuagbaw Lawrence
Published: April 2020

Background

As part of the scale-up of the Patient Care Collaborative (PCC) at our institution, we explored staff perceptions and patient outcomes at different levels of model implementation in three general internal medicine units.

Methods

We conducted a mixed-methods embedded experimental healthcare improvement initiative. In the qualitative strand, we conducted five focus group discussions. In the quantitative strand, we used hospital administrative data to compare outcomes (falls per 1000, median length of stay in days and resource use measured as resource intensity weights (RIW), before and after the implementation of the PCC, using χ2tests, Wilcoxon’s rank sum tests and interrupted time series analyses.

Results

Staff showed considerable knowledge and acceptance of the PCC but expressed mixed feelings with regards to patient safety, workload, communication and teamwork. Staff perceptions varied by level of implementation of the PCC. A number of falls (overall) in the full implementation phase were not significantly different from the preimplementation phase (227 per 1000 vs 200 per 1000; p=0.449), but the number of moderate to severe falls dropped (12 vs 2 per 1000); p<0.001). Median length of stay (5 vs 6 days; p<0.001) and resource use were lower (0.1 vs 0.4; p<0.001) in the full implementation phase compared with the preimplementation phase. The trend analyses showed differences across units.

Conclusions

The PCC was moderately well adopted. Perceptions of the PCC among staff and patient outcomes are likely linked to the levels of implementation. The PCC resulted in improved safety, shorter hospital stays and lower costs of care.
Framework for patient, family-centred care within an Australian Community Hospital: development and description
Authors: Frakking Thuy , Michaels Suzanne , Orbell-Smith Jane , Le Ray Lance
Published: April 2020

Objective

To describe the development of a patient and family-centred care (PFCC) conceptual framework within a small community Australian Hospital.

Methods

A scoping review of scientific and grey literature and community hospital stakeholder discussions were used to identify and design a conceptual framework for PFCC across five core pillars of leadership, engagement, service delivery, learning and environment.

Results

107 publications were identified and 76 were included for data extraction. A draft framework was constructed and modified following consultation with hospital stakeholders across a small Australian Community Hospital. The ‘Caring Together’ framework outlines three core layers: (1) the focus of our care is the experiences of our consumers and staff; (2) concepts of leadership, environment, service delivery, engagement and learning; and (3) the overarching fundamental values of being heard, respected, valued and supported by staff and consumers at all levels in an organisation.

Conclusions

The conceptual Caring Together framework structures key PFCC concepts across organisational priority areas within an Australian healthcare setting and can be used to guide implementation of PFCC at other small hospital facilities. Changes to national and state healthcare funding may help facilitate improved hospital facility implementation of PFCC, and ultimately improve consumer healthcare satisfaction and clinical outcomes.
Growth hormone treatment in Prader-Willi syndrome patients: systematic review and meta-analysis
Authors: Passone Caroline de Gouveia Buff , Franco Ruth Rocha , Ito Simone Sakura , Trindade Evelinda , Polak Michel , Damiani Durval , Bernardo Wanderley Marques
Published: April 2020

Background

Growth hormone (GH) treatment is currently recommended in Prader-Willi syndrome (PWS) patients.

Objectives

To evaluate the impact (efficacy and safety) of the use of recombinant human GH (rhGH) as a treatment for PWS.

Method

We performed a systematic review and, where possible, meta-analysis for the following outcomes: growth, body mass index, body composition, cognitive function, quality of life, head circumference, motor development/strength, behaviour and adverse effects. We included all PWS patients, with all types of genetic defects and with or without GH deficiency, who participated in rhGH studies performed in infancy, childhood and adolescence, that were either randomised controlled trials (RCTs) (double-blinded or not) or non-randomised controlled trials (NRCTs) (cohort and before and after studies). The databases used were MEDLINE, Embase and Cochrane Central.

Results

In 16 RCTs and 20 NRCTs selected, the treated group had an improvement in height (1.67 SD scores (SDS); 1.54 to 1.81); body mass index z-scores (−0.67 SDS; −0.87 to −0.47) and fat mass proportion (−6.5% SDS; −8.46 to −4.54) compared with the control group. Data about cognition could not be aggregated.

Conclusion

Based on high quality evidence, rhGH treatment favoured an improvement of stature, body composition and body mass index, modifying the disease’s natural history; rhGH treatment may also be implicated in improved cognition and motor development in PWS patients at a young age.

Ethics and dissemination

The current review was approved by the ethical committee of our institution. The results will be disseminated through conference presentations and publications in peer-reviewed journals.

PROSPERO registration number

CRD42019140295
Uptake of pre-symptomatic testing forBRCA1andBRCA2is age, gender, offspring and time-dependent
Authors: Forde Claire , Brunstrom Kate , Woodward Emma , Bowers Naomi , Pereira Marta , Wallace Andrew J , Lalloo Fiona , Harkness Elaine F , Evans D Gareth
Published: April 2020

Background

Genetic testing forBRCA1 and BRCA2pathogenic variants (PVs) has been available in North West England since 1995. We assessed uptake of pre-symptomatic testing in 1564 families with PVs over a 24.5year follow-up (FU) period.

Methods

First-degree relatives (FDRs) in families withBRCA1orBRCA2PVs were eligible from date of index family report if unaffected by a relevant cancer and alive at report date. FDRs were censored as not having undergone a pre-symptomatic test at diagnosis of a relevant cancer, date of death, age 93 or 30/03/2019. Time to uptake of pre-symptomatic testing was assessed by Kaplan–Meier curves, by gender and children.

Results

2554 male and 3115 female FDRs were eligible. Overall uptake was 775 (30.3%) in men and 1935 (62.1%) in women. This increased at 15 years to 33.6% and 67.9%, and continued to rise until 24 years (p<0.001). For women, the 29-year to 39-year age group had the highest uptake at 10 years FU (72.5%; p<0.01), whereas the 50-year to 59-year age group was highest in men (37.2%; p<0.01). Women <18 years at the time of familial variant identification had lower initial uptake, but this rose to >80% by 15 years. Uptake was higher in parous women (p<0.001) and in men with daughters (p<0.0001).

Conclusion

Uptake ofBRCA1/2pre-symptomatic testing is age, gender and time-dependent, and higher in women with children and men with daughters.
Value of choice
Authors: Walker Tom
Published: April 2020

Accounts of the value of patient choice in contemporary medical ethics typically focus on the act of choosing. Being the one to choose, it is argued, can be valuable either because it enables one to bring about desired outcomes, or because it is a way of enacting one’s autonomy. This paper argues that all such accounts miss something important. In some circumstances, it is having the opportunity to choose, not the act of choosing, that is valuable. That is because in many situations whether one has, or is denied, that opportunity conveys how one is seen. In particular, it conveys whether or not one is seen as an equal and competent member of society. Adequately recognising this fact has implications for what healthcare professionals should do, ones that require a move away from the current focus on autonomy. The paper draws out these implications by focusing on patients who may struggle to be recognised as competent and equal members of society, and whose autonomy may thus itself sometimes be in question.
ASPIRE-3-PREVENT: a cross-sectional survey of preventive care after a coronary event across the UK
Authors: Jennings Catriona S , Kotseva Kornelia , Bassett Paul , Adamska Agnieszka , Wood David
Published: April 2020

Objective

To quantify the implementation of the third Joint British Societies’ Consensus Recommendations for the Prevention of Cardiovascular Disease (JBS3) after coronary event.

Methods

Using a cross-sectional survey design, patients were consecutively identified in 36 specialist and district general hospitals between 6 months and 2 years, after acute coronary syndrome or revascularisation procedure and invited to a research interview. Outcomes included JBS3 lifestyle, risk factor and therapeutic management goals. Data were collected using standardised methods and instruments by trained study nurses. Blood was analysed in a central laboratory and a glucose tolerance test was performed.

Results

3926 eligible patients were invited to participate and 1177 (23.3% women) were interviewed (30% response). 12.5% were from black and minority ethnic groups. 45% were persistent smokers, 36% obese, 52.9% centrally obese, 52% inactive; 30% had a blood pressure >140/90 mm Hg, 54% non-high-density lipoprotein ≥2.5 mmol/L and 44.3% had new dysglycaemia. Prescribing was highest for antiplatelets (94%) and statins (85%). 81% were advised to attend cardiac rehabilitation (86% <60 years vs 79% ≥60 years; 82% men vs 77% women; 93% coronary artery bypass grafting vs 59% unstable angina), 85% attended if advised; 69% attended overall. Attenders were significantly younger (p=0.03) and women were less likely to attend (p=0.03).

Conclusions

Patients with coronary heart disease (CHD) are not being adequately managed after event with preventive measures. They require a structured preventive cardiology programme addressing lifestyle, risk factor management and adherence to cardioprotective medications to achieve the standards set by the British Association for Cardiovascular Prevention and Rehabilitation and JBS3 guidelines.
Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay
Authors: Sabiiti Wilber , Azam Khalide , Farmer Eoghan Charles William , Kuchaka Davis , Mtafya Bariki , Bowness Ruth , Oravcova Katarina , Honeyborne Isobella , Evangelopoulos Dimitrios , McHugh Timothy Daniel , Khosa Celso , Rachow Andrea , Heinrich Norbert , Kampira Elizabeth , Davies Geraint , Bhatt Nilesh , Ntinginya Elias N , Viegas Sofia , Jani Ilesh , Kamdolozi Mercy , Mdolo Aaron , Khonga Margaret , Boeree Martin J , Phillips Patrick P J , Sloan Derek , Hoelscher Michael , Kibiki Gibson , Gillespie Stephen H
Published: April 2020

In this comparative biomarker study, we analysed 1768 serial sputum samples from 178 patients at 4 sites in Southeast Africa. We show that tuberculosis Molecular Bacterial Load Assay (TB-MBLA) reduces time-to-TB-bacillary-load-result from days/weeks by culture to hours and detects early patient treatment response. By day 14 of treatment, 5% of patients had cleared bacillary load to zero, rising to 58% by 12th week of treatment. Fall in bacillary load correlated with mycobacterial growth indicator tube culture time-to-positivity (Spearmans r=−0.51, 95% CI (−0.56 to −0.46), p<0.0001). Patients with high pretreatment bacillary burdens (above the cohort bacillary load average of 5.5log10eCFU/ml) were less likely to convert-to-negative by 8th week of treatment than those with a low burden (below cohort bacillary load average), p=0.0005, HR 3.1, 95% CI (1.6 to 5.6) irrespective of treatment regimen. TB-MBLA distinguished the bactericidal effect of regimens revealing the moxifloxacin—20 mg rifampicin regimen produced a shorter time to bacillary clearance compared with standard-of-care regimen, p=0.008, HR 2.9, 95% CI (1.3 to 6.7). Our data show that the TB-MBLA could inform clinical decision making in real-time and expedite drug TB clinical trials.
Placement accuracy of resuscitative endovascular occlusion balloon into the target zone with external measurement
Authors: Matsumoto Shokei , Funabiki Tomohiro , Kazamaki Taku , Orita Tomohiko , Sekine Kazuhiko , Yamazaki Motoyasu , Moriya Takashi
Published: April 2020

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) should be safely placed at zone 1 or 3, depending on the location of the hemorrhage. Ideally, REBOA placement should be confirmed via fluoroscopy, but it is not commonly available for trauma bays. This study aimed to evaluate the accuracy of REBOA placement using the external measurement method in a Japanese trauma center.

Methods

A retrospective review identified all trauma patients who underwent REBOA and were admitted to our trauma center from 2008 to 2018. Patient characteristics, REBOA placement accuracy, and complications according to target zones 1 and 3 were reviewed.

Results

During the study period, 38 patients met our inclusion criteria. The in-hospital mortality rate was 57.9%. REBOA was mainly used for bleeding from the abdominal (44.7%) and pelvic (36.8%) regions. Of these, 30 patients (78.9%) underwent REBOA for target zone 1, and 8 patients (21.1%) underwent REBOA for target zone 3. The proportion of abdominal bleeding source in the target zone 1 group was greater than that in the target zone 3 group (56.7% vs. 0%). Overall, the proportion of REBOA placement was 76.3% in zone 1, 21.1% in zone 2, and 2.6% in zone 3. The total REBOA placement accuracy was 71.1%. At each target zone, the REBOA placement accuracy for target zone 3 was significantly lower than that for target zone 1 (12.5% vs. 86.7%, p<0.001). No significant associations between non-target zone placement and patient characteristics, complications, or mortality were found.

Conclusions

The REBOA placement accuracy for target zone 3 was low, and zone 2 placement accounted for 21.1% of the total, but no complications and mortalities related to non-target zone placement occurred. Further external validation study is warranted.

Level of evidence

Level IV.
Axial performance of micropile groups in cohesionless soil from full-scale tests
Authors: Abdlrahem Maged A. , El Naggar M. Hesham
Published: April 2020

Hollow bar micropile (HBMP) groups are used for supporting large loads as an alternative foundation option to large diameter drilled shafts. In such cases, it may be necessary to increase the micropile’s diameter by increasing the drill bit diameter (Db). This paper investigates experimentally and numerically the effect of increasing Dband micropile spacing on the group performance. A field load testing program was conducted on four groups of HBMPs installed in sand; each group comprised four micropiles arranged in a square configuration. All micropiles were constructed with the same size hollow bar, Dh= 51 mm; two groups comprised micropiles constructed with drill bit, Db= 115 mm, and two groups comprised micropiles constructed with drill bit, Db= 152 mm. One group of each set was installed with spacing to micropile diameter ratio, S/Db= 3 and the other group with S/Db= 5. In addition, full 3D finite element model (FEM) was developed and calibrated to simulate the behaviour of micropile groups and to evaluate the failure load for groups that were not loaded to failure. The results demonstrated that micropile groups constructed with the large diameter drill bits displayed higher stiffness and load carrying capacity than the groups constructed with small diameter bits, which confirms the effectiveness of using a larger drill bit. In addition, the group efficiency ratio values at both working load and ultimate capacity were found to be close to unity for all groups. The ultimate skin friction values of grouted micropiles obtained from this study were higher than the values suggested by the US Federal Highway Administration for medium to very dense sand. It was also found that the settlement of the 4-HBMP group increased by 25% to 33% over that of a single HBMP due to group effect.
Origin and paleoenvironmental reconstruction of phosphorus-bearing sandstones of the Cambrian Xinji Formation, southwestern margin of the Ordos Basin, China
Authors: Liang Jiwei , Tao Wenxing , Ma Xiaojun
Published: April 2020

Increasing exploration interest in oil and gas hosted by early Cambrian strata has focused research efforts on early Cambrian sandstones. The origin of phosphorus and the paleoenvironment of phosphorus-bearing sandstones from the Xinji Formation are discussed in this paper. X-ray diffraction, optical microscopy, grain size analysis, total organic carbon, and the concentrations of major, trace, and rare earth elements (REEs) are analyzed in this work. The sandstones are mostly sublitharenite with calcareous cement. The content of the sandstone samples is quartz (39.8%–73.9%), with illite (7.9%–27.6%) and calcite (4.5%–29%). The mineral particles of sandstone samples are mainly well sorted with a fine particle size, suggesting strong paleohydrodynamic force. The value of SiO2 is 37.69%–78.19%, followed by Al2O3 (6.11%–13.67%). Compared with upper continental crust, the boron in the sandstone samples is relatively enriched, whereas Sc, Sr, and Ba are relatively depleted. The ΣREE content is 124.46–323.99 ppm. Phosphorus is of biogenic origin and enriched by upwelling current. The source of the Xinji Formation sandstone samples was mainly a mixture of sedimentary rock, granite, and alkali basalt, with the provenance of terrestrial clastic materials. The sandstone was deposited under oxic conditions and a warm and humid paleoclimate with saline to brackish features on a passive continental margin. Phosphorus occurring in sandstones is sensitive to paleoclimate and can be used as an indicator to judge paleoclimate, as it is more enriched in warm and humid weather.
Tracking control of an underwater manipulator using fractional integral sliding mode and disturbance observer
Authors: Han Lijun , Tang Guoyuan , Xu Ruikun , Huang Hui , Xie De
Published: April 2020

In this paper, a fractional integral sliding mode control (FISMC) strategy with a disturbance observer (DO) is proposed for the trajectory tracking problem of the underwater manipulator, under lumped disturbances namely parameter uncertainties and external disturbances. The modified fractional integral sliding mode surface (FISMS) is designed to guarantee the fast convergence of system states. The DO method and the second-order sliding mode control law are used in the controller design, in which the former is introduced to compensate the effect of the lumped disturbances. Also, a saturated function is selected to replace the sign function to attenuate the chattering phenomenon. The stability of the overall closed-loop system is proved via Lyapunov’s finite-time stability theory. Numerical simulations are performed on a 6 degree of freedom (DOF) underwater manipulator. Simulation results demonstrate that the proposed control scheme can achieve better tracking performance and stronger robustness against disturbances, by comparing with the DO-based PD control and the DO-based PID-type linear sliding mode control (SMC).
Generalized scalar–tensor theory of gravity reconstruction from physical potentials of a scalar field
Authors: Fomin I. V. , Chervon S. V. , Tsyganov A. V.
Published: April 2020

We describe how to reconstruct generalized scalar–tensor gravity (GSTG) theory, which admits exact solutions for a physical type of potentials. Our consideration deals with cosmological inflationary models based on GSTG with non-minimal coupling of a (non-canonical) scalar field to the Ricci scalar. The basis of proposed approach to the analysis of these models is an a priori specified relation between the Hubble parameter H and a function of a non-minimal coupling $$F=1+\delta F$$F=1+δF, $$H\propto \sqrt{F}$$H∝F. Deviations from Einstein gravity $$\delta F$$δF induce corresponding deviations of the potential $$\delta V$$δV from a constant value and modify the dynamics from a pure de Sitter exponential expansion. We analyze the models with exponential power-law evolution of the scale factor and we find the equations of influence of non-minimal coupling, choosing it in the special form, on the potential and kinetic energies. Such a consideration allows us to substitute the physical potential into the obtained equations and then to calculate the non-minimal coupling function and kinetic term that define the GSTG parameters. With this method, we reconstruct GSTG for the polynomial, exponential, Higgs, Higgs–Starobinsky and Coleman–Weinberg potentials. Special attention we pay to parameters of cosmological perturbations and prove the correspondence of the obtained solutions to observational data from Planck.
Relativistic nucleon interaction with electromagnetic fields in 2 + 1 space-time dimensions
Authors: Bruce S. A. , Diaz-Valdes J. F.
Published: April 2020

The study of physical models within the framework of relativistic quantum mechanics in [Formula: see text] or [Formula: see text] space-time dimensions is often considered as a useful approach toward exploring real-world relativistic phenomena in [Formula: see text] space-time dimensions. This article presents the dynamics of a nucleon (which is either a neutron or a proton) with magnetic moment in the presence of certain electromagnetic fields in [Formula: see text] dimensions. In a polar coordinate, we examine four models described by the Dirac–Pauli equation: (i) neutron and proton harmonic oscillators; and (ii) neutron and proton hydrogen atom-like systems. We show that in some instances the energy eigenstates in noncentral potentials can be separable and exactly solvable. We present relativistic quantum-mechanical models of magnetic moments which can be further investigated.
Analysis of Laminated Plates Subjected to Mechanical and Hygrothermal Environmental Loads Using Fifth-Order Shear and Normal Deformation Theory
Authors: Naik Nitin S. , Sayyad Atteshamuddin S.
Published: April 2020

Bending analysis of laminated composite plates subjected to mechanical and hygrothermal environmental loading is presented in this paper using fifth-order shear and normal deformation theory (FOSNDT). This theory uses polynomial-type shape function in the displacement field up to fifth-order. This theory considers the effect of transverse normal deformations ([Formula: see text]). Simply supported laminated composite and sandwich plates are analyzed using Navier’s solution techniques. The results obtained using this theory are compared with the results available in the literature wherever possible. However, many results are presented for the first time in this paper.
A novel fluorogenic probe for visualizing the hydrogen peroxide in Parkinson’s disease models
Authors: Zhang Gaobin , Li Zheng , Chen Fangjie , Zhang Duoteng , Ji Wenhui , Yang Zhengpeng , Wu Qiong , Zhang Chengwu , Li Lin , Huang Wei
Published: April 2020

Parkinson’s disease (PD) is closely related to the oxidative stress induced by excess hydrogen peroxide (H2O2) in organisms. Developing an efficient method for noninvasive and real-time H2O2 detection is beneficial to investigate the role played by H2O2 in PD. In this work, a novel fluorogenic probe (CBH) for living organisms H2O2 detection has been designed, synthesized and characterized. The emission of CBH in PBS solution is very weak. However, when H2O2 was added, the fluorescence of CBH solution was sharply increased for 12-fold, accompanied by the emission peak blue-shifted from 600 to 530 nm. Moreover, the response of CBH to H2O2 is highly sensitive and selective and is not affected by various ROS/RNS, anions, cations, and amino acids. Based on the good performance of CBH for H2O2 detection, it has been successfully applied to visualizing the H2O2 concentration in living cells, Zebrafish and [Formula: see text]. elegans PD models.
The Category of Machines that Become Conscious
Authors: Aleksander Igor
Published: April 2020

A conscious machine category is defined for which the process of becoming conscious is important. This is distinguished from the artificial intelligence category of machines and contrasted with being a conscious living organism. An example is given of a neural automaton for which becoming conscious is seen to be equated to the growth of a depictive state structure. Existing works and future possibilities are examined against this categoric distinction.
Conscious AI at the Edge of Chaos
Authors: Bołtuć Piotr
Published: April 2020

The main problem for AI consciousness is to operate within the right kind of AI. We distinguish between the traditional computing (GOFAI), and the computing based on stochastic pattern optimization. The latter will be called here computing at the edge of chaos. Optimization of learning patterns, which is the gist of its success, often happens between the areas of too much repetitive order and those of hard to predict and control stochastic processes. This is to change the focus from the opposition of symbolic versus sub-symbolic computing; symbols can appear at different granularities and the hedge between The Physical Symbol System Hypothesis and neural nets seems no longer the most productive cut to make. Computing at the edge of chaos is promising for AGI, especially for AGI consciousness. The second problem for AI consciousness is to work with the right definitions of consciousness.
Attention and Consciousness in Intentional Action: Steps Toward Rich Artificial Agency
Authors: Bello Paul , Bridewell Will
Published: April 2020

If artificial agents are to be created such that they occupy space in our social and cultural milieu, then we should expect them to be targets of folk psychological explanation. That is to say, their behavior ought to be explicable in terms of beliefs, desires, obligations, and especially intentions. Herein, we focus on the concept of intentional action, and especially its relationship to consciousness. After outlining some lessons learned from philosophy and psychology that give insight into the structure of intentional action, we find that attention plays a critical role in agency, and indeed, in the production of intentional action. We argue that the insights offered by the literature on agency and intentional action motivate a particular kind of computational cognitive architecture, and one that hasn’t been well-explicated or computationally fleshed out among the community of AI researchers and computational cognitive scientists who work on cognitive systems. To give a sense of what such a system might look like, we present the ARCADIA attention-driven cognitive system as first steps toward an architecture to support the type of agency that rich human–machine interaction will undoubtedly demand.
Unpredictability of AI: On the Impossibility of Accurately Predicting All Actions of a Smarter Agent
Authors: Yampolskiy Roman V.
Published: April 2020

The young field of AI Safety is still in the process of identifying its challenges and limitations. In this paper, we formally describe one such impossibility result, namely Unpredictability of AI. We prove that it is impossible to precisely and consistently predict what specific actions a smarter-than-human intelligent system will take to achieve its objectives, even if we know the terminal goals of the system. In conclusion, the impact of Unpredictability on AI Safety is discussed.
Fear of a Bot Planet: Anthropomorphism, Humanoid Embodiment, and Machine Consciousness
Authors: Zebrowski Robin L.
Published: April 2020

There is an ongoing debate about the existence of humanoid robotics. The arguments tend to focus on the ethical claims that there is always deception involved. However, little attention has been paid to the ontological reasons that humanoid robotics are valuable in consciousness research. This paper examines the arguments and controversy around ethical rejection of humanoid robotics, while also summarizing some of the landscape of 4e cognition that highlights the ways our specific humanoid bodies in our specific cultural, social, and physical environments play an indispensable role in cognition, from conceptualization through communication. Ultimately, we argue that there is a compelling set of reasons to pursue humanoid robotics as a major research agenda in AI if the goal is to create an artificial conscious system that we will be able to both recognize as conscious and communicate with successfully.
Impact of Functionalization and Co-Additives on Dioxazolone Electrolyte Additives
Authors: Gauthier Roby , Hall David S. , Lin Katherine , Baltazar Jazmin , Hynes Toren , Dahn J. R.
Published: April 2020

Finding new electrolyte additives could help create lithium-ion batteries with better performance at high voltage, allowing higher energy density. However, finding the perfect additive remains a tremendous challenge, since researchers still don’t understand how to predict their performance. A new group of dioxazolone electrolyte additives have been tested in lithium-ion batteries alone or in combination with well-known co-additives. The new additives consist of a 3-phenyl-1,4,2-dioxazol-5-one (PDO) parent structure with or without (methoxy, fluoro and nitro) functional groups on the para position of the phenyl ring. It is found that PDO (no functional group) and p-(4-nitrophenyl)-1,4,2-dioxazol-5-one (pNDO) are the best performing dioxazolones overall and show promising results.
Maternal endothelial function, circulating endothelial cells, and endothelial progenitor cells in pregnancies conceived with or without in vitro fertilization
Authors: Conrad Kirk P. , Lingis Melissa , Sautina Larysa , Li Shiyu , Chi Yueh-Yun , Qiu Yingjie , Li Mingyue , Williams R. Stan , Rhoton-Vlasak Alice , Segal Mark S.
Published: April 2020

In women who conceived with or without assisted reproduction, we evaluated endothelial function by EndoPAT [reactive hyperemia index (RHI)], circulating numbers of endothelial cells (CEC) and endothelial progenitor cells (EPC), and their function before during and after pregnancy. In vitro fertilization (IVF) pregnancies were stratified by method of conception and corpus luteum (CL) number—controlled ovarian stimulation (>1 CL) or programmed (0 CL) cycles and spontaneous singleton pregnancies (1 CL). We observed 1) comparable gestational decline of RHI in the three participant groups secondary to gestational rise of baseline preocclusion pulse-wave amplitude (PWA) incorporated into the RHI calculation by EndoPAT software; 2) progressive rise in “normalized” RHI throughout pregnancy (calculated by substituting prepregnancy baseline preocclusion PWA into the RHI equation), greater in spontaneous conception vs. IVF cohorts; 3) similar gestational increase of maximum PWA and time to maximum PWA after the ischemia stimulus among the three participant groups; 4) modest gestational increase of ischemia response (reactive hyperemia) in the spontaneous conception group and no change or significant decline, respectively, in women who conceived using programmed or controlled ovarian stimulation cycles; 5) enhanced basal nitric oxide production by early (primitive) outgrowth EPC during pregnancy in women who conceived spontaneously, but not through IVF; and 6) gestational increase in CEC in all three participant cohorts, more pronounced in women who conceived by IVF using programmed cycles. On balance, the evidence supported enhanced endothelial function during pregnancy in spontaneous conceptions but less so in IVF pregnancies using either controlled ovarian stimulation or programmed cycles.
Skeletal muscle adaptations to heat therapy
Authors: Kim Kyoungrae , Monroe Jacob C. , Gavin Timothy P. , Roseguini Bruno T.
Published: April 2020

The therapeutic effects of heat have been harnessed for centuries to treat skeletal muscle disorders and other pathologies. However, the fundamental mechanisms underlying the well-documented clinical benefits associated with heat therapy (HT) remain poorly defined. Foundational studies in cultured skeletal muscle and endothelial cells, as well as in rodents, revealed that episodic exposure to heat stress activates a number of intracellular signaling networks and promotes skeletal muscle remodeling. Renewed interest in the physiology of HT in recent years has provided greater understanding of the signals and molecular players involved in the skeletal muscle adaptations to episodic exposures to HT. It is increasingly clear that heat stress promotes signaling mechanisms involved in angiogenesis, muscle hypertrophy, mitochondrial biogenesis, and glucose metabolism through not only elevations in tissue temperature but also other perturbations, including increased intramyocellular calcium and enhanced energy turnover. The few available translational studies seem to indicate that the earlier observations in rodents also apply to human skeletal muscle. Indeed, recent findings revealed that both local and whole-body HT may promote capillary growth, enhance mitochondrial content and function, improve insulin sensitivity and attenuate disuse-induced muscle wasting. This accumulating body of work implies that HT may be a practical treatment to combat skeletal abnormalities in individuals with chronic disease who are unwilling or cannot participate in traditional exercise-training regimens.
Sixteen weeks of testosterone with or without evoked resistance training on protein expression, fiber hypertrophy and mitochondrial health after spinal cord injury
Authors: Gorgey Ashraf S. , Graham Zachary A. , Chen Qun , Rivers Jeannie , Adler Robert A. , Lesnefsky Edward J. , Cardozo Christopher P.
Published: April 2020

Fiber cross-sectional area (CSA), protein expression, mitochondrial citrate synthase (CS), and succinate dehydrogenase (SDH) were measured following 16 wk of low-dose testosterone replacement therapy (TRT) with and without electrically evoked resistance training (RT) in men with spinal cord injury (SCI). Fiber CSA and protein expression of total GLUT4, total Akt, and phosphorylated Akt increased following TRT + RT but not in the TRT-only group. Mitochondrial CS and SDH increased after TRT + RT but not in TRT-only group.
Phosphate Transport in Epithelial and Nonepithelial Tissue
Authors: Hernando Nati , Gagnon Kenneth , Lederer Eleanor
Published: April 2020

Phosphate is an essential nutrient for life and is a critical component of bone formation, a major signaling molecule, and structural component of cell walls. Phosphate is also a component of high-energy compounds (i.e., AMP, ADP, and ATP) and essential for nucleic acid helical structure (i.e., RNA and DNA). Phosphate plays a central role in the process of mineralization, normal serum levels being associated with appropriate bone mineralization, while high and low serum levels are associated with soft tissue calcification. The serum concentration of phosphate and the total body content of phosphate are highly regulated, a process that is accomplished by the coordinated effort of two families of sodium-dependent transporter proteins. The three isoforms of the SLC34 family (SLC34A1–A3) show very restricted tissue expression and regulate intestinal absorption and renal excretion of phosphate. SLC34A2 also regulates the phosphate concentration in multiple lumen fluids including milk, saliva, pancreatic fluid, and surfactant. Both isoforms of the SLC20 family exhibit ubiquitous expression (with some variation as to which one or both are expressed), are regulated by ambient phosphate, and likely serve the phosphate needs of the individual cell. These proteins exhibit similarities to phosphate transporters in nonmammalian organisms. The proteins are nonredundant as mutations in each yield unique clinical presentations. Further research is essential to understand the function, regulation, and coordination of the various phosphate transporters, both the ones described in this review and the phosphate transporters involved in intracellular transport.
Study on Form-Finding of Cable-Membrane Structures Based on Particle Swarm Optimization Algorithm
Authors: Sun Fangjin , Zhu Donghan , Liang Meirong , Zhang Daming
Published: April 2020

Form-finding is one of the key steps in the whole design process of cable-membrane structures. Traditional form-finding methods are usually complicated and have poor accuracy or stability. Thus, form-finding of cable-membrane structures based on particle swarm optimization (PSO) algorithm is proposed. The shape and loading characteristics of cable-membrane structures are optimized. The optimization objective is to minimize the maximum support reaction, and the initial prestress on the membrane surface is taken as the optimization variable. The main constraints are material strength limitation, structural stress, and displacement of the cable and membrane. A program is given based on the proposed PSO, and the optimization model and calculation process are implemented based on MATLAB and ANSYS platforms. Form-finding of three typical cable-membrane structures including rotating catenary surface, saddle surface, and rhombic hyperboloid is carried out. The results compare well with those from the force density method. The initial prestresses of the three membrane structures are obtained while the form-finding result is optimal, respectively. The proposed PSO shows a more accurate method in form-finding of cable-membrane structures in a simpler way.
Antibiotic Resistance and Molecular Epidemiological Characteristics of Streptococcus agalactiae Isolated from Pregnant Women in Guangzhou, South China
Authors: Cheng Zhaomin , Qu Pinghua , Ke Peifeng , Yang Xiaohan , Zhou Qiang , Lan Kai , He Min , Cao Nannan , Qin Sheng , Huang Xianzhang
Published: April 2020

Streptococcus agalactiae colonization in pregnant women can cause postpartum intrauterine infections and life-threatening neonatal infections. To formulate strategies for the prevention and treatment of S. agalactiae infections, we performed a comprehensive analysis of antibiotic resistance and a molecular-based epidemiological investigation of S. agalactiae in this study. Seventy-two S. agalactiae strains, collected from pregnant women, were subjected to antibiotic susceptibility tests; then, the screened erythromycin and clindamycin nonsusceptible isolates were used for macrolides and clindamycin resistance genes detection, respectively. Detection of resistance genes, serotyping, and determination of virulence genes were performed by polymerase chain reaction. The clonal relationships among the colonized strains were evaluated by multilocus sequence typing. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) mass peak analysis was performed to discriminate the specific sequence types (STs). In our study, 69.4% and 47.2% of the strains were nonsusceptible to erythromycin and clindamycin, respectively; the multidrug resistance rate was 66.7%. All erythromycin nonsusceptible strains harbored resistance genes, whereas only 52.9% of the clindamycin nonsusceptible strains possessed the linB gene. Erythromycin resistance was mainly mediated by the ermB or mefA/E genes. Four serotypes were identified, and the most common serotype was serotype III (52.8%), followed by Ib (22.2%), Ia (18.0%), and II (4.2%). All the strains were divided into 18 STs that were assigned to nine clonal complexes. Most of the major STs were distributed into specific serotypes, including ST19/serotype III, ST17/serotype III, ST485/serotype Ia, ST862/serotype III, and ST651/serotype III. Analysis of virulence genes yielded seven clusters, of which bca-cfb-scpB-lmb (61.6%) was the predominant virulence gene cluster. Among all ST strains distributed in this region, only the ST17 strains had a mass peak at 7620 Da. The outcomes of this study are beneficial for the epidemiological comparison of colonized S. agalactiae in different regions and may be helpful for developing the strategies for the prevention of S. agalactiae infection in Guangzhou. Furthermore, our results show that MALDI-TOF MS can be used for the rapid identification of the ST17 strains.
Transcriptional Sequencing and Gene Expression Analysis of Various Genes in Fruit Development of Three Different Black Pepper (Piper nigrumL.) Varieties
Authors: Khew Choy Yuen , Harikrishna Jennifer Ann , Wee Wei Yee , Lau Ee Tiing , Hwang Siaw San
Published: April 2020

Black pepper (Piper nigrum) is a vital spice crop with uses ranging from culinary to pharmacological applications. However, limited genetic information has constrained the understanding of the molecular regulation of flower and fruit development in black pepper. In this study, a comparison among three different black pepper varieties, Semengok Aman (SA), Kuching (KC), and Semengok 1 (S1), with varying fruit characteristics was used to provide insight on the genetic regulation of flower and fruit development. Next-generation sequencing (NGS) technology was used to determine the flower and fruit transcriptomes by sequencing on an Illumina HiSeq 2500 platform followed byde novoassembly using SOAPdenovo-Trans. The high-quality assembly of 66,906 of unigenes included 64.4% of gene sequences (43,115) with similarity to one or more protein sequences from the GenBank database. Annotation with Blast2Go assigned 37,377 genes to one or more Gene Ontology terms. Of these genes, 5,874 genes were further associated with the biological pathways recorded in the KEGG database. Comparison of flower and fruit transcriptome data from the three different black pepper varieties revealed a large number of DEGs between flower and fruit of the SA variety. Gene Ontology (GO) enrichment analysis further supports functions of DEGs between flower and fruit in the categories of carbohydrate metabolic processes, embryo development, and DNA metabolic processes while the DEGs in fruit relate to biosynthetic process, secondary metabolic process, and catabolic process. The enrichment of DEGs in KEGG pathways was also investigated, and a large number of genes were found to belong to the nucleotide metabolism and carbohydrate metabolism categories. Gene expression profiling of flower formation-related genes reveals that other than regulating the flowering in black pepper, the flowering genes might also be implicated in the fruit development process. Transcriptional analysis of sugar transporter and carbohydrate metabolism genes in different fruit varieties suggested that the carbohydrate metabolism in black pepper fruit is developmentally regulated, and some genes might serve as potential genes for future crop quality improvement. Study on the piperine-related gene expression analysis suggested that lysine-derived products might present in all stages of fruit development, but the transportation was only active at the early stage of fruit development. These results indicate several candidate genes related to the development of flower and fruit in black pepper and provide a resource for future functional analysis and potentially for future crop improvement.