Combining frequency and time domain approaches to systems with multiple spike train input and output

A frequency domain approach and a time domain approach have been combined in an investigation of the behaviour of the primary and secondary endings of an isolated muscle spindle in response to the activity of two static fusimotor axons when the parent muscle is held at a fixed length and when it is subjected to random length changes. The frequency domain analysis has an associated error process which provides a measure of how well the input processes can be used to predict the output processes and is also used to specify how the interactions between the recorded processes contribute to this error. Without assuming stationarity of the input, the time domain approach uses a sequence of probability models of increasing complexity in which the number of input processes to the model is progressively increased. This feature of the time domain approach was used to identify a preferred direction of interaction between the processes underlying the generation of the activity of the primary and secondary endings. In the presence of fusimotor activity and dynamic length changes imposed on the muscle, it was shown that the activity of the primary and secondary endings carried different information about the effects of the inputs imposed on the muscle spindle. The results presented in this work emphasise that the analysis of the behaviour of complex systems benefits from a combination of frequency and time domain methods

The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis

LM has received grants by the Faculty of Medicine at the RWTH Aachen University (START 15/14 and START 46/16) and the Deutsche Forschungsgemeinschaft (DFG, MA 7082/1–1). This work was supported by the Immunohistochemistry and Confocal Microscopy Unit, a core facility of the Interdisciplinary Centre for Clinical Research (IZKF) Aachen, within the Faculty of Medicine at the RWTH Aachen University and the RWTH centralized Biomaterial Database (RWTH cBMB) of the University Hospital RWTH Aachen. We are very grateful to Antons Martincuks M.Sc. and Professor Gerhard Müller-Newen for live-cell imaging. This work was supported, in part, by the University of Turin (ex-60% 2015A and B) and by the William Harvey Research Foundation and forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit that is supported and funded by the National Institute for Health Research. This work also contributes to the Organ Protection research theme of the Barts Centre for Trauma Sciences supported by the Barts and The London Charity (Award 753/1722)

A case of serendipity*

An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of “trigger” events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed

Basal cell carcinoma of the vulva: a case report and systematic review of the literature

The vulva is an unusual site for basal cell carcinoma (BCC). Vulvar BCC accounts for <1% of all BCCs and <5% of all vulvar malignancies. We report the case of an 83 year‐old woman who presented with a 2‐month history of a tender labial growth, with histopathology confirming nodular BCC. We conducted a systematic literature review of the characteristics of reported cases of vulvar BCCs. A comprehensive systematic review of articles indexed for MEDLINE and Embase yielded 96 reports describing 437 patients with 446 BCCs of the vulva. The mean age at presentation was 70 (range 20–100). Most women had no underlying vulvar disease. Approximately 60% of cases were of the nodular subtype. Treatment approach varied widely with over half of cases treated with wide local or local excision. Mohs micrographic surgery (MMS) for vulvar BCC was first reported in 1988 with seven total MMS cases reported. Twenty‐three cases of recurrence have been reported; 21 of these cases after local excision but none following MMS. Vulvar BCC is a rarely reported cancer that affects older women predominantly. MMS represents a promising treatment for BCC in this anatomic location.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150570/1/ijd14307.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150570/2/ijd14307_am.pd

Guidelines on Chemotherapy in Advanced Stage Gynecological Malignancies: An Evaluation of 224 Professional Societies and Organizations

BACKGROUND: Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. METHODS: We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. RESULTS: Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. CONCLUSIONS: Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence

Usability Testing of a Reusable Pulse Oximeter Probe Developed for Health-Care Workers Caring for Children < 5 Years Old in Low-Resource Settings

Hypoxemia measured by pulse oximetry predicts child pneumonia mortality in low-resource settings (LRS). Existing pediatric oximeter probes are prohibitively expensive and/or difficult to use, limiting LRS implementation. Using a human-centered design, we developed a low-cost, reusable pediatric oximeter probe for LRS health-care workers (HCWs). Here, we report probe usability testing. Fifty-one HCWs from Malawi, Bangladesh, and the United Kingdom participated, and seven experts provided reference measurements. Health-care workers and experts measured the oxygen saturation (SpO2) independently in < 5 year olds. Health-care worker measurements were classed as successful if recorded in 5 minutes (or shorter) and physiologically appropriate for the child, using expert measurements as the reference. All expert measurements were considered successful if obtained in < 5 minutes. We analyzed the proportion of successful SpO2 measurements obtained in < 1, < 2, and < 5 minutes and used multivariable logistic regression to predict < 1 minute successful measurements. We conducted four testing rounds with probe modifications between rounds, and obtained 1,307 SpO2 readings. Overall, 67% (876) of measurements were successful and achieved in < 1 minute, 81% (1,059) < 2 minutes, and 90% (1,181) < 5 minutes. Versus neonates, increasing age (infant adjusted odds ratio [aOR]; 1.87, 95% confidence interval [CI]: 1.16, 3.02; toddler aOR: 4.33, 95% CI: 2.36, 7.97; child aOR; 3.90, 95% CI: 1.73, 8.81) and being asleep versus being calm (aOR; 3.53, 95% CI: 1.89, 6.58), were associated with < 1 minute successful measurements. In conclusion, we designed a novel, reusable pediatric oximetry probe that was effectively used by LRS HCWs on children. This probe may be suitable for LRS implementation

Evaluating privacy-preserving record linkage using cryptographic long-term keys and multibit trees on large medical datasets.

Background: Integrating medical data using databases from different sources by record linkage is a powerful technique increasingly used in medical research. Under many jurisdictions, unique personal identifiers needed for linking the records are unavailable. Since sensitive attributes, such as names, have to be used instead, privacy regulations usually demand encrypting these identifiers. The corresponding set of techniques for privacy-preserving record linkage (PPRL) has received widespread attention. One recent method is based on Bloom filters. Due to superior resilience against cryptographic attacks, composite Bloom filters (cryptographic long-term keys, CLKs) are considered best practice for privacy in PPRL. Real-world performance of these techniques using large-scale data is unknown up to now. Methods: Using a large subset of Australian hospital admission data, we tested the performance of an innovative PPRL technique (CLKs using multibit trees) against a gold-standard derived from clear-text probabilistic record linkage. Linkage time and linkage quality (recall, precision and F-measure) were evaluated. Results: Clear text probabilistic linkage resulted in marginally higher precision and recall than CLKs. PPRL required more computing time but 5 million records could still be de-duplicated within one day. However, the PPRL approach required fine tuning of parameters. Conclusions: We argue that increased privacy of PPRL comes with the price of small losses in precision and recall and a large increase in computational burden and setup time. These costs seem to be acceptable in most applied settings, but they have to be considered in the decision to apply PPRL. Further research on the optimal automatic choice of parameters is needed

Evolution, and functional analysis of Natural Resistance-Associated Macrophage proteins (NRAMPs) from Theobroma cacao and their role in cadmium accumulation

The presence of the toxic metal cadmium (Cd2+) in certain foodstuffs is recognised as a global problem, and there is increasing legislative pressure to reduce the content of Cd in food. The present study was conducted on cacao (Theobroma cacao), the source of chocolate, and one of the crops known to accumulate Cd in certain conditions. There are a range of possible genetic and agronomic methods being tested as a route to such reduction. As part of a gene-based approach, we focused on the Natural Resistance-Associated Macrophage Proteins (NRAMPS), a family of proton/metal transporter proteins that are evolutionarily conserved across all species from bacteria to humans. The plant NRAMP gene family are of particular importance as they are responsible for uptake of the nutritionally vital divalent cations Fe2+, Mn2+, Zn2+, as well as Cd2+. We identified the five NRAMP genes in cacao, sequenced these genes and studied their expression in various organs. We then confirmed the expression patterns in response to variation in nutrient cation availability and addition of Cd2+. Functional analysis by expression in yeast provided evidence that NRAMP5 encoded a protein capable of Cd2+ transport, and suggested this gene as a target for genetic selection/modification

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty