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Background: The arteriovenous fistula (AVF) is the preferred vascular access for End Stage Renal Disease, having superior patency and lower infection risks than prosthetic graft and catheter access. When AVF dysfunction or delayed maturation does occur, the gold standard for diagnosis is the fistula angiogram (a.k.a. fistulogram). 3D ultrasound is available for obstetrical and other specialized uses, but it is cost prohibitive and has a field of view that is too small to cover the region of interest for the dialysis fistula application. We sought to develop a point of care 3D solution using freehand 2D ultrasound data acquisition., Methods: We developed open-source software for 3D image reconstruction and projection of an angiogram-like image of the vascular access using a 2D freehand ultrasound scanner. We evaluated this software by comparing the ultrasound "sono-angiogram" images to fistulogram images in five subjects, using visual inspection and by applying the Percent of Exact Match (PEM) as a statistic test., Results: The sono-angiograms showed identifiable characteristics that matched the fistulogram results in all five subjects. The PEM ranged between 42.8% and 77.0%, with Doppler and grayscale ultrasound data, showing complementary advantages and disadvantages when used for sono-angiogram image construction. Motion from freehand ultrasound acquisition was a significant source of mismatch. 3D image generation is a potential advantage with ultrasound data., Conclusions: While further work is needed to improve the accuracy with free hand scanning, fistulogram-like "sono-angiograms" can be generated using point of care 2D ultrasound. Methods such as these may be able to assist in point-of-care diagnosis in the future. The software is open-source, and importantly, the ultrasound data used are non-proprietary and available from any standard ultrasound machine. The simplicity and accessibility of this approach warrant further study., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The purpose of this study was to examine the relationship between psychological factors (depression, anxiety, and catastrophizing) and fear of falling avoidance behavior (FFAB) among individuals with Parkinson's disease (PD)., Methods: A secondary analysis of cross-sectional data from 59 individuals with PD using hierarchical multiple regression., Results: Disease severity (Movement Disorder Society - Unified PD Rating Scale) and catastrophizing (Consequences of Falling Questionnaire (CoF)) explained approximately 48.2% of the variance in the FFAB Questionnaire scores ( P < .001). Catastrophizing was the only significant psychological variable ( P < .001). The damage to identity subscale of the CoF was significant in the final model ( P < .001)., Conclusions: Catastrophizing about the consequences of falls explained the largest portion of variability in FFAB after controlling for disease severity. Catastrophizing about the immediate consequences of falling may play a prominent role in FFAB and may be a potential treatment target for mitigating FFAB.

Introduction: Dialysis vascular access, preferably an autogenous arteriovenous fistula, remains an end stage renal disease (ESRD) patient's lifeline providing a means of connecting the patient to the dialysis machine. Once an access is created, the current gold standard of care for maintenance of vascular access is angiography and angioplasty to treat stenosis. While point of care 2D ultrasound has been used to detect access problems, we sought to reproduce angiographic results comparable to the gold standard angiogram (fistulogram) using ultrasound data acquired from a conventional 2D ultrasound scanner., Methods: A 2D ultrasound probe was used to acquire a series of cross sectional images of the vascular access including arteriovenous anastomosis of a subject with a radio-cephalic fistula. These 2D B-mode images were used for 3D vessel reconstruction by binary thresholding to categorize vascular versus non-vascular structures followed by standard image segmentation to select the structure representative of dialysis vascular access and morphologic filtering. Image processing was done using open source Python Software., Results: The open source software was able to: (1) view the gold standard fistulogram images, (2) reconstruct 2D planar images of the fistula from ultrasound data as viewed from the top, analogous to computerized tomography images, and (3) construct a 2D representation of vascular access similar to the angiogram., Conclusion: We present a simple approach to obtain an angiogram-like representation of the vascular access from readily available, non-proprietary 2D ultrasound data in the point of care setting. While the sono-angiogram is not intended to replace angiography, it may be useful in providing 3D imaging at the point of care in the dialysis unit, outpatient clinic, or for pre-operative planning for interventional procedures. Future work will focus on improving the robustness and quality of the imaging data while preserving the straightforward freehand approach used for ultrasound data acquisition.

We used novel open source software, based on an ultrasound speckle tracking algorithm, to examine the distensibility of the vessel wall of the inflow artery, anastomosis, and outflow vein before and after two procedures. An 83-year-old white man with a poorly maturing radio-cephalic fistula received an angioplasty at the anastomosis followed by branch ligation 28 days later. Duplex Doppler measurements corroborated the blood flow related changes anticipated from the interventions. The experimental distensibility results showed that it is technically feasible to measure subtle vessel wall motion changes with high resolution (sub-millimeter) using standard Digital Imaging and Communications in Medicine (DICOM) ultrasound data, which are readily available on conventional ultrasound scanners. While this methodology was originally developed using high resolution radiofrequency from ultrasound data, the goal of this study was to use DICOM data, which makes this technology accessible to a wide range of users.

Purpose: Research supports holistic expansion of the construct of resourcefulness by adding spiritual practices to the existing personal and social dimensions. This study describes the development and testing of items to measure spiritual resourcefulness. Methods/Design: Study phases were: (1) focus group development of item stems and responses; (2) expert testing; (3) scale construction; (4) field testing in 234 family caregivers; and (5) psychometric analysis to identify items for inclusion in a final scale. Findings: A focus group developed 40 item stems with potential responses reflecting three conceptual components of spiritual practices (rational, ritualistic, and relational). Content experts selected the best response for each item. A six-point Likert scale consistent with the Resourcefulness Scale © was constructed. Data from field testing were factor analyzed. The best solution revealed two factors containing 12 items. Ritualistic and relational items loaded together (44.7% variance explained). Rational items loaded separately (19.5% variance explained). Higher-order factor analysis indicated the two subscales reflected a single construct (71.93% variance explained; r  = .44, p  < .001). Conclusion: Availability of a psychometrically sound measure of spiritual resourcefulness is critical to expand resourcefulness training interventions to be more holistic. Clinical interventions can be enriched by including strategies to enhance personal, social, and spiritual resourcefulness skills.

Complementary therapies are increasingly integrated into hospice care, emphasizing the need to examine the evidence regarding implementation and effects on end-of-life outcomes. This review synthesizes the evidence regarding the implementation of complementary therapies and effects on end-of-life outcomes in hospice care. Whittemore and Knafl's five-step integrative review process was applied. Using predefined search terms, research-based articles between 2006 and 2020 were reviewed. Twenty-three quantitative/mixed method studies conducted across eight countries met the final review criteria. Most commonly used complementary therapies were music, biofield therapies (reiki, therapeutic touch), and massage therapy. Most studies reported significant findings on physical symptoms (pain, dyspnea, fatigue, gastrointestinal symptoms, agitation) and/or psychosocial/spiritual symptoms (anxiety, depression, spirituality, well-being, quality of life); 40% of studies had both significant and nonsignificant findings. Methodological limitations included study design (few randomized controlled trials), small sample size, high attrition rate, lack of racial/ethnic diversity, unstandardized intervention implementation, and multiple outcome measurement instruments. Complementary therapies are promising components of hospice care; however, rigorous studies are needed to validate the effect on end-of-life outcomes and determine the most efficacious implementation. Complementary therapy studies face challenges consistent with end-of-life research; however, efforts to design rigorous trials and address methodological issues are required to enhance the state of the science., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

Although caregiver identity theory asserts there is no single generic caregiver identity, comparisons on demographic characteristics and burden of care have not been made among caregivers of persons with various health conditions. Using social media to access study participants, this cross-sectional study of 234 family caregivers of persons with various health conditions examined their demographic characteristics (age, gender, and race/ethnicity) and burden of care (daily care hours and caregiving years) using online data collection. Nine groups of caregivers were formed by the care recipient's health condition. Caregiver groups were similar in gender (95% women) and race/ethnicity (88% white), and differed on age (F=4.74; p<.001) daily care hours, and caregiving years (F's=2.76 and 2.84; p<.01). The findings suggest that caution is needed when recruiting caregivers through social media as the sample may not represent all caregivers. However, differences by care recipient condition on age and burden of care warrant further consideration.

Purpose: To examine the effects of prayer and meditation on the episodic memory of older adults. Design: Secondary analysis of Health and Retirement Study (HRS). Method: Drawing from a subsample of HRS ( n = 1,135), this study utilized generalized estimating equation regression models to examine the effects of meditation and prayer on changes in episodic memory of older adults over time. Findings: Findings show a statistically significant positive effect of the use of prayer (0.50, p < .05) on episodic memory score at baseline. We also observed a slight gain in episodic memory over time for older adults who used prayer (0.04, p = .05). Meditation was not found to have a statistically significant effect on changes in memory in later life. Conclusion: This study illustrates the benefits of prayer in preserving memory and provides much needed empirical basis for community-level interventions to enhance memory in later life.

Background: The use of complementary and alternative medicine (CAM) has increased and little is known on CAM use during the initial period. Therefore, the aim was to determine prevalence of CAM use among newly diagnosed breast cancer patients prior to seeking conventional treatment., Methods: This is a cross-sectional study involved interviewing newly diagnosed breast cancer patients in the University Malaya Medical Centre (UMMC) using a structured questionnaire. Eligible respondents were interviewedduring a routine clinical visit., Results: A total of 400 patients were interviewed, of whom 139 (34.8%) were CAM users. Dietary supplementation (n = 107, 77.0%) was the most frequently used type of CAM, followed by spiritual healing (n = 40, 28.8%) and traditional Chinese medicine (n = 32, 23.0%). Malay ethnic group (n = 61, 43.9%) was the largest group of CAM users, followed by Chinese (n = 57, 41.0%) and Indian (n = 20, 14.4%). Majority of these CAM users (n = 87, 73.1%) did not disclose the use of CAM to their doctors. Most of them used remedies based on the recommendation of family and friends. Malay ethnicity and patients with 3 or more comorbidities were more likely to use CAM., Conclusion: There is substantial use of CAM among breast cancer patients in UMMC prior to seeking hospital treatment, and the most popular CAM modality is dietary supplements. Since, the majority of CAM users do not disclose the use of CAM to their physicians, therefore health care providers should ensure that those patients who are likely to use CAM are appropriately counseled and advised.

Background: This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype., Methods: Unmedicated subjects with treatment-resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software. The amygdala, hippocampus, and thalamus were selected a priori for analysis. All subjects received a single 0.5mg/kg × 40-minute ketamine infusion. Pearson correlations were performed with subcortical volumes and percent change in MADRS score (from baseline to 230 minutes, 1 day, and 1 week post-infusion)., Results: Raw and corrected subcortical volumes did not correlate with antidepressant response at any timepoint. In val/val subjects ( n=23), corrected left and right thalamic volume positively correlated with antidepressant response to ketamine at 230 minutes post-infusion but did not reach statistical significance. In met carriers ( n=14), corrected left and right thalamic volume negatively correlated with antidepressant response to ketamine., Conclusion: Baseline subcortical volumes implicated in MDD did not correlate with ketamine's antidepressant efficacy. Baseline thalamic volume and BDNF genotype may be a combinatorial rapid antidepressant response biomarker.

This present study examined the hemostatic efficacy of nanofibrous matrix in a rat liver model. The nanofibrous matrix comprising gelatin and polycaprolactone was prepared by electrospinning method. Twelve animals underwent surgery and were followed-up for a month. Time taken to cease bleeding, activated partial thromboplastin time, prothrombin time, and fibrinogen concentration were measured. Histopathological examination of liver was also done of treated and control animals. All test animals showed very rapid hemostasis after application of electrospun sheet. Histopathological study showed quick recovery of liver wound in the test group as compared to the control group. The nanofibrous matrix has proven to be not only safe and effective as hemostat but has also shown its potential for liver regeneration.

Providing care for an elder with dementia can produce extreme stress that adversely affects caregiver health. Learning to be resourceful, which involves practicing resourcefulness skills using a journal or voice recorder, may reduce caregiver stress. However, before testing the effectiveness of journaling and voice recording as resourcefulness training (RT) practice methods, intervention fidelity should first be established. This pilot trial with 63 women dementia caregivers examined the fidelity of journaling and voice recording and whether allowing a choice between the methods affected RT intervention fidelity. Following RT, Resourcefulness Scale scores were similar for journal and recorder methods but higher for caregivers in the choice versus random condition. Patterns of RT skill use documented in journals or recordings were similar for choice and random conditions and for journal and recorder methods. The results support the implementation fidelity of RT that allows caregivers to choose a method to reinforce their resourcefulness skills., (© The Author(s) 2016.)

Objectives: The aims of this study were to develop a new method for analysis and presentation of esophageal distensibility data using high-resolution impedance planimetry recordings during a volume-controlled distention., Methods: Two control subjects and six patients with eosinophilic esophagitis (EoE) with stricture, narrow caliber or normal endoscopy according to EndoFLIP studies were included for analysis. Median filtering and pulse detection techniques were applied to the pressure signal and a wavelet decomposition technique was applied to the 16 channels of raw esophageal diameter data to reduce vascular artifact, respiratory effect and remove esophageal contraction interference. These data were used to generate a functional luminal imaging probe (FLIP) topography plot that describes regional variation of cross-sectional area (CSA). A previously developed computer program was used to calculate and model the CSA-pressure data to derive the slope of line fitting and distension plateau for each individual subject. The results were compared among the four endoscopic phenotypes., Results: Patients with EoE and normal endoscopy had similar esophageal distensibility parameters to those of normal controls whereas patients with EoE and stricture or narrow caliber had much lower distensibility than patients with EoE and normal endoscopy. The FLIP topography plots provided a global assessment of the esophageal distensibility along the axial plane of measurement that differentiated patients with varying degrees of endoscopic abnormality., Conclusions: New techniques can be leveraged to improve data analysis and presentation using EndoFLIP assessment of the esophageal body in EoE. These techniques may be helpful in defining clinically relevant phenotypes and guiding treatment strategies and should be helpful in structuring future outcome trials.

Signaling pathways are the fundamental grammar of cellular communication, yet few frameworks are available to analyze molecular imaging probes in the context of signaling pathways. Such a framework would aid in the design and selection of imaging probes for measuring specific signaling pathways and, vice versa, help illuminate which pathways are being assayed by a given probe. RAMP (Researching imaging Agents through Molecular Pathways) is a bioinformatics framework for connecting signaling pathways and imaging probes using a controlled vocabulary of the imaging targets. RAMP contains signaling pathway data from MetaCore, the Kyoto Encyclopedia of Genes and Genomes, and the Gene Ontology project; imaging probe data from the Molecular Imaging and Contrast Agent Database (MICAD); and tissue protein expression data from The Human Protein Atlas. The RAMP search tool is available at . Examples are presented to demonstrate the utility of RAMP for pathway-based searches of molecular imaging probes.

The American Academy of Pediatrics recommends renal ultrasound (RUS) and voiding cystourethrography (VCUG) for all infants after a first urinary tract infection (UTI). However, many congenital renal anomalies are identified by a prenatal US. At the present time, there are no data regarding the yield of post-UTI imaging among infants who have a documented normal prenatal US. We retrospectively reviewed the charts of all patients <1 year of age with a first UTI who had normal kidneys noted on prenatal US to determine the frequency of abnormal findings. Abnormal RUS and VCUG results were noted in 5.1% (24 of 471) and 20.4% (75 of 368) of infants, respectively. While the abnormal US rate is significantly less than what has been previously reported, the frequency of abnormal VCUGs is similar. These results suggest that a post-UTI RUS may not be needed if the prenatal US was normal. However, a VCUG continues to be indicated.

Phenotype-driven mouse mutagenesis programmes are widely advocated as a means of assigning functions to human genes. These programmes often give rise to a number of animal welfare concerns, not least the large numbers of animals that are used. Here, we consider how the phenotyping screens used in all such programmes can be improved, with specific reference to the standard phenotyping procedures described by the European Mouse Phenotyping Resource of Standardised Screens (EMPReSS). Although we commend the efforts of the Consortium in developing standardised screens for phenotyping, animal welfare should take precedence over technical ease and the cost implications of the research. A number of recommendations are made that could reduce the suffering of the mice used in such studies. These include the use of minimally invasive practices, reduced sample sizes, and combining the assays used in such studies., (2008 FRAME.)

At the request of the Food Standards Agency, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) established a Working Group on Variation and Uncertainty in Toxicology (WG VUT). In April 2006, the WG VUT produced a draft report for public consultation. FRAME made a submission in response to this consultation in July 2006. We commend the WG VUT for its comprehensive account of many of the problems associated with risk assessment, and for making recommendations about the problems that need to be addressed. We were particularly encouraged by the WG VUTs recognition of the need for guidelines on how toxicological studies should be conducted and data analysed. However, we believe that the report has not achieved all of its objectives. It does not adequately consider how modern technologies, experimental design, statistical analysis and species extrapolation can be used in practice to address variability and uncertainty. There is a disproportionate focus on the sources of variability and uncertainty in human data, with relatively little consideration of how variation and uncertainty due to animal tests can be addressed. Furthermore, it is clear that, until the advantages and limitations of all toxicological methods are fully appraised and testing strategies and guidelines are agreed, the scope for improving the existing approaches to risk assessment will be severely limited. Hence, the use of alternative methods for hazard identification and characterisation merit more consideration than they were given in the draft report.

The impetus to develop useful models of human disease and toxicity has resulted in a number of large-scale mouse mutagenesis programmes. This, in turn, has stimulated considerable concern regarding the scientific validity and welfare of genetically altered mice, and the large numbers of mice that are required by such programmes. In this paper, the scientific advantages and limitations of genetically altered mice as models of several human diseases are discussed. We conclude that, while the use of some such mouse models has contributed considerably to an understanding of human disease and toxicity, other genetically altered mouse models have limited scientific relevance, and fewer have positively contributed to the development of novel human medicines. Suggestions for improving this unsatisfactory situation are made.

In the last issue of ATLA, we assessed whether the existing methods for assessing the safety and efficacy of new candidate medicines was adequate for the testing of humanised therapeutic agents. We made specific reference to the failed TGN1412 first-in-man study that took place earlier this year. This paper was circulated to experts and those involved in the development or testing of TGN1412. More recently, the Focus on Alternatives group has made a submission to the Expert Working Group that is currently considering how such incidences can be avoided in the future. Here, we provide an update of the events relating to the TGN1412 clinical trial.

Clinical studies in human volunteers are an essential part of drug development. These studies are designed to account for possible differences between the effects of pharmaceutical products in preclinical studies and in humans. However, the tragic outcome of the recent Phase 1 clinical trial on TGN1412 casts considerable doubt over the relevance of this traditional drug development paradigm to the testing of therapeutic agents for human use. The role of alternatives to animal testing is considered, and a series of recommendations are made, which could ensure that clinical trials are well informed and based on the most relevant scientific information.

The 2004 Statistics of Scientific Procedures on Living Animals were released by the Home Office in December 2005. They indicate that, for the third year running, there has been a significant increase in the number of laboratory animal procedures undertaken in Great Britain, and that increasing numbers of animals are involved. The overall trends in the use of toxicological and non-toxicological procedures involving animals are described. Particular emphasis is placed on the production and use of genetically modified animals, the production of biological materials, and acute toxicity testing. The use of non-human primates and dogs is also discussed. The implications of these latest statistics are considered with reference to the implementation of the Three Rs and their consequences for animal welfare.

The Home Office have circulated a document that summarises the discussions of a Primate Stakeholders Forum. The Forum took place in January 2004, and was convened to address the issues raised and the recommendations made in the Animal Procedures Committee 2002 report on the use of primates under the Animals (Scientific Procedures) Act 1986. The report emphasises the need for more resources focused on alternatives to toxicological testing in primates, including harmonising worldwide regulatory requirements, investigating the relevance of primate models, and improving the retrospective analysis of procedures involving primates. The document called for reasoned comments about the report to be submitted to the Home Office. In response, FRAME submitted a comprehensive paper, which evaluated each of the Animal Procedures Committees recommendations, along with the Home Office Forums comments. FRAME believes that, in coming to a decision as to whether primates should be used for regulatory testing, there must be full consideration of all the information available, including whether the ethological needs of any given species can be met prior to, during and following experimental use. Where these needs cannot be met, there must be a concerted effort to develop alternative models for research and testing. However, this should not detract from the ultimate goal of phasing out primate research altogether.

The Academy of Medical Sciences, the Medical Research Council, the Royal Society and the Wellcome Trust are undertaking a study into the use of non-human primates in biological and medical research. An independent working group of scientific experts, led by Sir David Weatherall, aims to produce a report summarising the findings of this study, early in 2006. The trends in primate research, and the nature and effects of recent and proposed changes in the global use of non-human primates in research, will be investigated. The associated ethical, welfare and regulatory issues, and the role and impact of the Three Rs principles of refinement, reduction and replacement will also be reviewed. As part of this study, a call for evidence was made. The evidence submitted by FRAME emphasised that the use of non-human primates for fundamental research or for regulatory testing still fails to take into account the fact that, although non-human primates are anatomically and physiologically similar to humans, they are not necessarily relevant models for studies on human disease or human physiology. FRAME continues to believe that we have a duty to ensure that these animals are not used without overwhelming evidence that they are the only suitable and relevant models for use in work of undeniable significance.

At the beginning of 2005, the European Commission published its fourth report on the statistics of the number of animals used for experimental and other scientific purposes. A total of 10.7 million animals were used within the Member States of the European Union (EU) in 2002, an increase of almost a million animals since the 1999 report. France, Germany and the UK continue to be the largest users of animals for scientific purposes, and mice, rats, fish and birds remain the most commonly-used animals. For the first time, all 15 Member States used the standardised EU tables, as had been agreed in 1998. This has made it easier to identify areas on which Three Rs initiatives should be focused. Nevertheless, the reporting system still has a number of serious deficiencies. In particular, there are insufficient data on the numbers of animals that are kept or bred for research purposes, the numbers of transgenic animals, and the severity of procedures that are applied.

The statistics for animal procedures performed in 2003 were recently released by the Home Office. They indicate that, for the second year running, there was a significant increase in the number of laboratory animal procedures undertaken in Great Britain. The species and genera used, the numbers of toxicology and non-toxicology procedures, and the overall trends, are described. The implications of these latest statistics are discussed with reference to key areas of interest and to the impact of existing regulations and pending legislative reforms.