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Apatite-type oxides have been attracting interest as a new class of oxide ion conductors. In this paper we examine the effect of Ga doping on the conductivity of the apatite silicate system, Nd9.33+xSi6O26+3x/2 and compare the results to those reported for similar doping studies in La9.33+xSi6O26+3x/2. The highest conductivities are observed for samples containing oxygen excess, which is in agreement with previous reports that interstitial oxide ions are important for high oxide ion conduction in these materials. For oxygen stoichiometric materials, i.e. Nd9.33+x/3Si6-xGaxO26, the Ga doping results in a significant increase in activation energy and a consequent lowering of the low temperature conductivity. This is contrary to results previously reported for the La containing analogues, which showed an enhancement of conductivity on Ga doping up to x=1.5. Possible explanations for the differences between the two systems are discussed. [ABSTRACT FROM AUTHOR]

Apatite-type oxides of formula (La/Sr)10−xSi6O26+y have been attracting significant interest recently, because of their high oxide ion conductivity. In this paper we report the synthesis and conductivities of phases based on doping La9.33Si6O26 with Co, Fe, Mn on the Si site, according to the formula La9.33+x/3Si6−xMxO26 (M=Co, Fe, Mn). Substitution limits observed were x≤1.5 (Co), x≤1.25 (Fe), x≤0.5 (Mn). Higher Mn levels could be achieved by substituting onto the La site, with it being possible to prepare the phase La8Mn2Si6O26. The highest conductivities were observed for the Co doped samples, although investigations into the dependence of conductivity on p(O2) (0.2–10−5 atm.) indicated that the conductivity was dominated by the electronic component in these cases. In contrast, the conductivities for the Fe and Mn doped samples were mainly ionic in the same p(O2) range. Experiments into varying the oxygen content of these doped phases indicated that increasing the oxygen content above the nominally stoichiometric O26 appears to increase the oxide ion conductivity. Preliminary studies of the reactivity of the electrolyte La9.33Si6O26 with potential SOFC cathode materials (La1−xSrxMO3; M=Co, Fe, Mn) suggests that reaction can occur at high temperatures leading to the incorporation of the transition metal into the apatite electrolyte. However, the fact that these doped phases exhibit high conductivities suggests that this may limit any problems caused by such a reaction at the electrolyte-electrode interface. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic neurological condition and the leading cause of non-traumatic disability in young adults. MS pathogenesis leads to the death of oligodendrocytes, demyelination, and progressive central nervous system neurodegeneration. Endogenous remyelination occurs in people with MS (PwMS) but is insufficient to repair the damage. Our preclinical studies in mice indicate that endogenous remyelination can be supported by the delivery of repetitive transcranial magnetic stimulation (rTMS). Our phase I trial concluded that 20 sessions of rTMS, delivered over 5 weeks, are safe and feasible for PwMS. This phase II trial aims to investigate the safety and preliminary efficacy of rTMS for PwMS., Methods: Participants must be aged 18-65 years, diagnosed with MS by a neurologist, stable and relapse free for 6 months, have an Extended Disability Status Scale (EDSS) between 1.5 and 6 (inclusive), willing to travel to a study site every weekday for 4 consecutive weeks, and able to provide informed consent and access the internet. Participants from multiple centres will be randomised 2:1 (rTMS to sham) stratified by sex. The intervention will be delivered with a Magstim Rapid2 stimulator device and circular 90-mm coil or MagVenture MagPro stimulator device with C100 circular coil, positioned to stimulate a broad area including frontal and parietal cortices. For the rTMS group, pulse intensity will be set at 18% (MagVenture) or 25% (Magstim) of maximum stimulator output (MSO), and rTMS applied as intermittent theta burst stimulation (iTBS) (~ 3 min per side; 600 pulses). For the sham group, the procedure will be the same, but the intensity is set at 0%. Each participant will attend 20 intervention sessions over a maximum of 5 weeks. Outcome measures include MS Functional Composite Score (primary), Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Quality of Life, and Pittsburgh Sleep Quality Index/Numeric Rating Scale and adverse events (secondary) and advanced MRI metrics (tertiary). Outcomes will be measured at baseline and after completing the intervention., Discussion: This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in PwMS., Trial Registration: Registered with Australian New Zealand Clinical Trials Registry, 20 January 2022; ACTRN12622000064707., (© 2024. The Author(s).)

This article addresses the objective, experimental design and methodology of the tests conducted for battery State of Health (SOH) estimation using an accelerated test method. For this purpose, 25 unused cylindrical cells were aged, by continual electrical cycling using a 0.5C charge and 1C discharge to 5 different SOH breakpoints (80, 85, 90, 95 and 100%). Ageing of the cells to the different SOH values was undertaken at a temperature of 25 °C. A reference performance test (RPT) of C/3 charge-discharge at 25 °C was performed when the cells were new and at each stage of cycling to define the energy capacity reduction due to increased charge-throughput. An electrochemical impedance spectroscopy (EIS) test was performed at 5, 20, 50, 70 and 95% states of charge (SOC) for each cell at temperatures of 15, 25 and 35 °C. The shared data includes the raw data files for the reference test and the measured energy capacity and the measured SOH for each cell. It contains the 360 EIS data files and a file which tabulates the key features of the EIS plot for each test case. The reported data has been used to train a machine-learning model for the rapid estimation of battery SOH discussed in the manuscript co-submitted (MF Niri et al., 2022). The reported data can be used for the creation and validation of battery performance and ageing models to underpin different application studies and the design of control algorithms to be employed in battery management systems (BMS)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023 Published by Elsevier Inc.)

The American Physical Therapy Association Academy of Pediatric Physical Therapy (APTA Pediatrics) Research Agenda was updated in spring 2021. This article describes the process used to revise the agenda. A task force of the APTA Pediatrics Research Committee methodically reviewed and revised the 2018-2020 agenda document to reflect the current research priorities important for the field. The research priorities from various federal agencies such as the National Institutes of Health were reviewed and were aligned with the agency research priorities and goals. The agenda was revised based on feedback from task force members, and further revisions were made based on input from select members of APTA Pediatrics and other stakeholders. After incorporating inputs, the agenda was accepted as the APTA Pediatrics Research Agenda for the next 3 years and was shared with the membership on the APTA Pediatrics Research Web site., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Background: Sexual dysfunction following stroke is common but often is poorly managed. As awareness of sexual dysfunction following stroke increases as an important issue, a clearer evidence base for interventions for sexual dysfunction is needed to optimise management., Objectives: To evaluate the effectiveness of interventions to reduce sexual dysfunction following stroke, and to assess adverse events associated with interventions for sexual dysfunction following stroke., Search Methods: We conducted the search on 27 November 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; from June 2014), in the Cochrane Library; MEDLINE (from 1950); Embase (from 1980); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982); the Allied and Complementary Medicine Database (AMED; from 1985); PsycINFO (from 1806); the Physiotherapy Evidence Database (PEDro; from 1999); and 10 additional bibliographic databases and ongoing trial registers., Selection Criteria: We included randomised controlled trials (RCTs) that compared pharmacological treatments, mechanical devices, or complementary medicine interventions versus placebo. We also included other non-pharmacological interventions (such as education or therapy), which were compared against usual care or different forms of intervention (such as different intensities) for treating sexual dysfunction in stroke survivors., Data Collection and Analysis: Two review authors independently selected eligible studies, extracted data, and assessed study quality. We determined the risk of bias for each study and performed a 'best evidence' synthesis using the GRADE approach., Main Results: We identified three RCTs with a total of 212 participants. We noted significant heterogeneity in interventions (one pharmacological, one physiotherapy-based, and one psycho-educational), and all RCTs were small and of 'low' or 'very low' quality. Based on these RCTs, data are insufficient to provide any reliable indication of benefit or risk to guide clinical practice in terms of the use of sertraline, specific pelvic floor muscle training, or individualised sexual rehabilitation., Authors' Conclusions: Use of sertraline to treat premature ejaculation needs to be tested in further RCTs. The lack of benefit with structured sexual rehabilitation and pelvic floor physiotherapy should not be interpreted as proof of ineffectiveness. Well-designed, randomised, double-blinded, placebo-controlled trials of long-term duration are needed to determine the effectiveness of various types of interventions for sexual dysfunction. It should be noted, however, that it may not be possible to double-blind trials of complex interventions., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Tracking the deformation of fiducial markers in the vicinity of living cells embedded in compliant synthetic or biological gels is a powerful means to study cell mechanics and mechanobiology in three-dimensional environments. However, current approaches to track and quantify three-dimensional (3D) fiducial marker displacements remain ad-hoc, can be difficult to implement, and may not produce reliable results. Herein, we present a compact software package entitled "FM-Track," written in the popular Python language, to facilitate feature-based particle tracking tailored for 3D cell micromechanical environment studies. FM-Track contains functions for pre-processing images, running fiducial marker tracking, and post-processing and visualization. FM-Track can thus aid the study of cellular mechanics and mechanobiology by providing an extensible software platform to more reliably extract complex local 3D cell contractile information in transparent compliant gel systems.

Valve interstitial cells (VIC) are the primary cell type residing within heart valve tissues. In many valve pathologies, VICs become activated and will subsequently profoundly remodel the valve tissue extracellular matrix (ECM). A primary indicator of VIC activation is the upregulation of α-smooth muscle actin (αSMA) stress fibers, which in turn increase VIC contractility. Thus, contractile state reflects VIC activation and ECM biosynthesis levels. In general, cell contraction studies have largely utilized two-dimensional substrates, which are a vastly different micro mechanical environment than 3D native leaflet tissue. To address this limitation, hydrogels have been a popular choice for studying cells in a three-dimensional environment due to their tunable properties and optical transparency, which allows for direct cell visualization. In the present study, we extended the use of hydrogels to study the active contractile behavior of VICs. Aortic VICs (AVIC) were encapsulated within poly(ethylene glycol) (PEG) hydrogels and were subjected to flexural-deformation tests to assess the state of AVIC contraction. Using a finite element model of the experimental setup, we determined the effective shear modulus μ of the constructs. An increase in μ resulting from AVIC active contraction was observed. Results further indicated that AVIC contraction had a more pronounced effect on μ in softer gels (72 ± 21% increase in μ within 2.5 kPa gels) and was dependent upon the availability of adhesion sites (0.5-1 mM CRGDS). The transparency of the gel allowed us to image AVICs directly within the hydrogel, where we observed a time-dependent decrease in volume (time constant τ=3.04 min) when the AVICs were induced into a hypertensive state. Our results indicated that AVIC contraction was regulated by both the intrinsic (unseeded) gel stiffness and the CRGDS peptide concentrations. This finding suggests that AVIC contractile state can be profoundly modulated through their local micro environment using modifiable PEG gels in a 3D micromechanical-emulating environment. Moving forward, this approach has the potential to be used towards delineating normal and diseased VIC biomechanical properties using highly tunable PEG biomaterials. STATEMENT OF SIGNIFICANCE., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs. Using 24 retinopathy cases and 97 controls with no clinical signs of retinopathy, we replicated the chromosome 17 association in Swedish Vallhunds from the UK and aimed to elucidate the causal variant underlying this association using whole genome sequencing (WGS) of an affected dog. This revealed a 6-8 kb insertion in intron 1 of MERTK that was not present in WGS of 49 dogs of other breeds. Sequencing and BLASTN analysis of the inserted segment was consistent with the insertion comprising a full-length intact LINE-1 retroelement. Testing of the LINE-1 insertion for association with retinopathy in the UK set of 24 cases and 97 controls revealed a strong statistical association (P-value 6.0 x 10-11) that was subsequently replicated in the original Finnish study set (49 cases and 89 controls (P-value 4.3 x 10-19). In a pooled analysis of both studies (73 cases and 186 controls), the LINE-1 insertion was associated with a ~20-fold increased risk of retinopathy (odds ratio 23.41, 95% confidence intervals 10.99-49.86, P-value 1.3 x 10-27). Our study adds further support for regulatory disruption of MERTK in Swedish Vallhund retinopathy; however, further work is required to establish a functional overexpression model. Future work to characterise the mechanism by which this intronic mutation disrupts gene regulation will further improve the understanding of MERTK biology and its role in retinal function.

The aim was to create an environment where doctors at all levels felt like an important part of the education team. Two teaching fellows were appointed to deliver teaching, encourage participation, and quality-assure teaching. An innovative electronic logbook named Teaching Log (T-Log) was developed to reliably "record and reward" teaching occurring at all career levels. A mentor scheme for medical students was established. Mentor training was provided for junior doctors. A near-peer teaching programme was developed for final year medical students on important skills required to be a safe junior doctor. Between September 2013 and January 2014, 83 doctors at our institution logged 657 teaching episodes using the electronic T-Log. 23% were F1s, 14% were F2s, 24% CT1-2s. 36% of sessions were delivered to 3rd year medical students and 36% were delivered to 5th year students. 24% were small group seminars, 26% were bedside teaching sessions, 12% were lectures, 5% were simulation sessions and 9% were clinical skills. 20% of sessions were delivered to a single student. 100% of respondents (15) agreed that T-Log was easy to use. 100% agreed that T-Log was useful. 100% agreed that they would continue to use T-Log. A survey found the mean score for usefulness of the mentor scheme to be 9.1 (1=not useful, 10=very useful). Students saw their mentors on average 6.5 times during a 10 week period. Confidence scores for all key areas of the curriculum were increased following implementation of the scheme. 100% of students would recommend this scheme to next year's final year students and 100% of mentor respondents (n=8) would participate in the scheme again. Rewarding those who contribute to teaching provides incentive to further increase the quality of education provided to students. T-Log rewards teaching activity. It also provides useful data at an individual level or at institutional level.

A 3-year-old, neutered male Tiffany cat was presented to the Animal Health Trust for investigation of pyrexia and a gastric lesion. Radiography and ultrasound showed severe thickening of the gastric wall and regional lymphadenopathy. There was altered gastric wall layering, predominately due to muscularis thickening. Histopathology confirmed eosinophilic fibrosing gastritis. The cat also had evidence of generalised Toxoplasma gondii infection, which may have been responsible for the gastric changes.

Objective: To determine whether there was an association between hypertensive retinopathy and high systolic, diastolic, and mean arterial blood pressures in cats., Animals: 181 cats., Procedure: Systolic, diastolic, and mean arterial blood pressures were measured by use of a noninvasive oscillometric technique. The range of blood pressure measurements in healthy cats from various age groups was determined. Associations among systolic, diastolic, and mean arterial blood pressure; hypertensive retinopathy; hyperthyroidism; left ventricular cardiac hypertrophy; chronic renal failure; and serum biochemical abnormalities were determined., Results: All blood pressure measurements increased with age in healthy cats. The frequency of hypertensive retinopathy also increased with age and with blood pressure, and hypertensive retinopathy was particularly found in cats with systolic blood pressures > 168 mm Hg. There was an increased risk for hypertensive retinopathy in cats that were female, > 10 years old, and neutered. The risk of chronic renal failure also increased as blood pressure, particularly systolic blood pressure, increased., Conclusions and Clinical Relevance: Hypertensive retinopathy was common in cats > or = 10 years of age and was associated with systolic blood pressures > 168 mm Hg when measured by the noninvasive oscillometric technique.

The effect of the nitric oxide (NO) donor SIN-1 on energy metabolism was examined in three murine transplantable tumours in vivo using 31P MRS. SIN-1 at 2 mg kg-1 i.v. reduced Pi/total by 40-50% in SCCVII/Ha and KHT tumours within 5 min of injection, returning to control levels by 20 min. However, this dose of SIN-1 did not consistently alter Pi/total in RIF-1 tumours. Reduction in Pi/total in SCCVII/Ha tumours 10 min after 5 mg kg-1 i.v. SIN-1 was similar to that for 2 mg kg-1. SIN-1 at 10 mg kg-1 had no effect on Pi/total at 10 min after injection, but increased this ratio 2-fold over control at 60 min, at which time no effect of the lower doses of SIN-1 were observed. SIN-1 effects on SCCVII/Ha tumour response to X-rays were also examined, using an in vivo/in vitro clonogenic assay 24 h after treatment. SIN-1 at 0.5-2 mg kg-1 i.v. given immediately before irradiation increased tumour cell killing 2-4-fold over that for 15 Gy X-rays alone, while higher SIN-1 doses were ineffective. The results indicate that NO donors can alter tumour energy metabolism and X-ray response in a manner consistent with increased oxygenation. However, these responses are dependent upon dose, timing and tumour type.

In the present study, we have investigated insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in serum and artificially raised blister fluid from uninvolved and involved areas of nine patients with psoriasis. Both levels of IGFs and IGFBP-3, and profiles of IGFBP in serum and fluid from the uninvolved areas of these patients were comparable to those seen in normal subjects. In fluid from the involved areas, the IGF-II but not IGF-I level was significantly elevated. Among five molecular forms of IGFBP, the density of 41.5- and 38.5-kDa forms of IGFBP-3 were apparently increased in fluid from the involved areas, shown by Western ligand blotting. Radioimmunoassay further showed that the IGFBP-3 concentration in the involved areas was significantly raised. Immunoblotting revealed that the predominant form of IGFBP-3 in fluid from the uninvolved areas was a 29-kDa proteolytically modified product. In contrast, intact doublet IGFBP-3 was the main form of IGFBP-3 in fluid from the involved areas. Fluid from the involved areas but not the matched serum concentration-dependently inhibited the degradation of 125I-labeled nonglycosylated IGFBP-3 (ngIGFBP-3) caused by fluid from the uninvolved areas, suggesting the presence of an IGFBP-3 protease inhibitor(s) in psoriatic skin lesion. These findings suggest that the alterations in IGF/IGFBP system may contribute to the pathogenesis of psoriasis.

The nitric oxide synthase inhibitor NG-nitro-L-arginine (NOARG) was examined for its ability to alter energy metabolism in three murine tumors using 31P magnetic resonance spectroscopy. NOARG (10 mg/kg, i.v.) increased the inorganic phosphate:total phosphate ratio (Pi:total) 2-3-fold in the KHT, RIF-1, and SCCVII/Ha intradermal back tumors from 30 min to 6 h after injection, but the 31P magnetic resonance spectrum from normal tissue on the mouse back was unchanged after this treatment. NOARG (10 mg/kg, i.v.) injected 30 min before X-rays increased tumor cell survival 3-5-fold in SCCVII/Ha and 50-200-fold in RIF-1, measured using an in vivo/in vitro clonogenic assay. These effects were equivalent to those obtained from clamped tumors, indicating full radiobiological hypoxia. In KHT, only a 2-fold increase in radioresistance was observed after NOARG, which was less than the response of clamped tumors. In RIF-1 tumors, NOARG induced full radiobiological hypoxia when given from 30 min to 6 h prior to X-rays, consistent with the time course for the increase in Pi:total, measured by 31P magnetic resonance spectroscopy. Pi:total after NOARG doses of 0.1-10 mg/kg, i.v., increased in a dose-dependent manner in this tumor. Increased RIF-1 tumor radioresistance was similarly dependent on NOARG dose. The combination of the bioreductive agent RB6145 (300 mg/kg, i.p.) 15 min prior to NOARG (10 mg/kg, i.v.) produced greater than 5 decades of KHT tumor cell killing at 24 h after treatment. This combination also increased Pi:total 4.5-fold over the control value at 24 h in the KHT tumor. Histological examination of tumors at this time indicated extensive necrosis.

The effect of combining photodynamic therapy (PDT) and bioreductive drugs has been investigated using the RIF-1 experimental murine tumour. Light was delivered interstially to the tumour at 675 nm using a single optical fibre attached to an argon-ion dye laser. The photosensitizer was disulphonated aluminium phthalocyanine (AlS2Pc) and the bioreductive drugs were the dual function nitroimidazole RSU1069 and its pro-drug RB6145. Varying the time between administration of the photosensitizer and light delivery (TL) from 30 min to 24 h had little influence on the extent of the anti-tumour effect of PDT alone, as measured by the regrowth delay endpoint. When the bioreductive drug was included in the treatment, administered 20 min before light irradiation, regrowth delay was greatly increased. The effectiveness of the combined treatment was optimum for short values of TL (about 1 h). Fluorescence microscopy was used to investigate the distribution of the photosensitizer within the tumours. This showed that the compound was mainly confined to the tumour vasculature over the first few hours post-treatment. The high efficacy of the combined treatment of PDT and bioreductive drugs for short values of TL suggest that photodynamic action, during the period when the photosensitizer AlS2Pc is confined to the vasculature, enhances the severity of tumour hypoxia which is sufficient to induce activation of the bioreductive drugs.

The production and quality control of ALG are outlined. The advantages and disadvantages of the various routes of administration of ALG are discussed. We tend to use a short duration high dose course of ALG in renal transplantation, myasthenia gravis and polyarteritis nodosa.

In controlled randomized study of antilymphocyte globulin (ALG) in 100 cadaveric renal transplants, 15 patients receiving a second transplant were excluded. Ofthe first transplants, 42 were in the control and 43 in the ALG group. The two groups were similar. The ALG used was either prodduced in our laboratories or obtained from a commerical source. It was observed that ALG produced a significant lymphopenia, that the oliguric phase of the ALG group was half that of the controls, and that the ALG group although less likely to suffer rejection episodes responded significantly better when treated than did those in the control group.