Nonlinear multilevel dynamics of a coupled SQUID ring-resonator system in the hysteretic regime

We consider the dynamical behavior of a strongly hysteretic SQUID ring coupled to a radio frequency resonator. By experiment we show that this system can display novel multiple level structures in its rf voltage-current characteristics which are solutions of the nonlinear equations of motion describing the system

Non-linear Multi-level Dynamics of a SQUID Ring-resonator System in the Hysteretic Regime

We consider the dynamical behavior of a strongly hysteretic SQUID ring coupled to a radio frequency resonator. By experiment we show that this system can display novel multiple level structures in its rf voltage-current characteristics which are solutions of the nonlinear equations of motion describing the system

Subnormothermic perfusion with h2s donor ap39 improves dcd porcine renal graft outcomes in an ex vivo model of kidney preservation and reperfusion

This is the final published version, also available from MDPI via the DOI in this record.Cold preservation is the standard of care for renal grafts. However, research on alterna-tives like perfusion at higher temperatures and supplementing preservation solutions with hydrogen sulfide (H2S) has gained momentum. In this study, we investigated whether adding H2S donor AP39 to porcine blood during subnormothermic perfusion at 21 °C improves renal graft outcomes. Porcine kidneys were nephrectomized after 30 min of clamping the renal pedicles and treated to 4 h of static cold storage (SCS) on ice or ex vivo subnormothermic perfusion at 21 °C with autologous blood alone (SNT) or with AP39 (SNTAP). All kidneys were reperfused ex vivo with autologous blood at 37 °C for 4 h. Urine output, histopathology and RNAseq were used to evaluate the renal graft function, injury and gene expression profiles, respectively. The SNTAP group exhibited significantly higher urine output than other groups during preservation and reperfusion, along with significantly lower apoptotic injury compared to the SCS group. The SNTAP group also exhibited differential pro-survival gene expression patterns compared to the SCS (downregulation of pro-apoptotic genes) and SNT (downregulation of hypoxia response genes) groups. Subnormothermic perfusion at 21 °C with H2S-supplemented blood improves renal graft outcomes. Further research is needed to facilitate the clinical translation of this approach.Medical Research Council (MRC)Physicians Services Incorporated (PSI) FoundationLawson Research Institut

Multidisciplinary paper on patient blood management in cardiothoracic surgery in the UK: perspectives on practice during COVID-19

The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

Salivary exRNA biomarkers to detect gingivitis and monitor disease regression

AimThis study tests the hypothesis that salivary extracellular RNA (exRNA) biomarkers can be developed for gingivitis detection and monitoring disease regression.Materials and MethodsSalivary exRNA biomarker candidates were developed from a total of 100 gingivitis and nonâ gingivitis individuals using Affymetrix’s expression microarrays. The top 10 differentially expressed exRNAs were tested in a clinical cohort to determine whether the discovered salivary exRNA markers for gingivitis were associated with clinical gingivitis and disease regression. For this purpose, unstimulated saliva was collected from 30 randomly selected gingivitis subjects, the gingival and plaque indexes scores were taken at baseline, 3 and 6 weeks and salivary exRNAs were assayed by means of reverse transcription quantitative polymerase chain reaction.ResultsEight salivary exRNA biomarkers developed for gingivitis were statistically significantly changed over time, consistent with disease regression. A panel of four salivary exRNAs [SPRR1A, lncâ TET3â 2:1, FAM25A, CRCT1] can detect gingivitis with a clinical performance of 0.91 area under the curve, with 71% sensitivity and 100% specificity.ConclusionsThe clinical values of the developed salivary exRNA biomarkers are associated with gingivitis regression. They offer strong potential to be advanced for definitive validation and clinical laboratory development test.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144647/1/jcpe12930.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144647/2/jcpe12930_am.pd

The effect of occupational exposure to solar ultraviolet radiation on malignant skin melanoma and non- melanoma skin cancer: a systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

A systematic review and meta-analysis of studies were conducted reporting on the association between occupational exposure to solar ultraviolet radiation (UVR) and both malignant skin melanoma (melanoma) and non-melanoma skin cancer (NMSC), with the aim of enabling the estimation of the numbers of deaths and disability-adjusted life years from melanoma and NMSC attributable to occupational exposure to solar UVR, for the development of the World Health Organization (WHO)/International Labour Organization (ILO) Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). A protocol was developed and published, applying the Navigation Guide as an organizing systematic review framework where feasible. Electronic bibliographic databases were searched for potentially relevant records; electronic grey literature databases and organizational websites were also searched, reference lists of previous systematic reviews and included study records were hand-searched, and additional experts were consulted. Randomized controlled trials and cohort, case–control and other non-randomized studies were included that estimated the effect of any occupational exposure to solar UVR, compared with no occupational exposure to solar UVR, on melanoma (excluding melanoma of the lip or eye) or NMSC prevalence, incidence or mortality. At least two reviewers independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage. Adjusted relative risks were combined using random-effects meta-analysis. Two or more reviewers assessed the risk of bias, quality of evidence and strength of evidence. Fifty-three (48 case–control, three case–case and two cohort) eligible studies were found, published in 62 study records, including over 457 000 participants in 26 countries of three WHO regions (Region of the Americas, European Region and Western Pacific Region), reporting on the effect on melanoma or NMSC incidence or mortality. No studies on the prevalence of melanoma or NMSC were found. In most studies, exposure was self-reported in questionnaires during interviews and the health outcome was assessed via physician diagnosis based on biopsy and histopathological confirmation. The risk of bias of the body of evidence was judged to be generally “probably low”, although there were some concerns regarding risks of exposure misclassification bias, detection bias and confounding. The main meta-analyses of relevant case–control studies revealed a relative risk (RR) of melanoma and NMSC incidence of 1.45 (95% confidence interval (CI): 1.08–1.94; I2 = 81%) and 1.60 (95% CI: 1.21–2.11; I2 = 91%), respectively. No statistically significant differences in risk of melanoma and NMSC incidence were found when conducting subgroup analyses by WHO region, and no differences in risk of NMSC incidence in a subgroup analysis by sex. However, in a subgroup analysis by NMSC subtype, the increased risk of basal cell carcinoma (RR: 1.50; 95% CI: 1.10–2.04; 15 studies) was probably lower (P = 0.05 for subgroup differences) than the increased risk for squamous cell carcinoma (RR: 2.42; 95% CI: 1.66–3.53; 6 studies). The sensitivity analyses found that effect estimates of NMSC incidence were significantly higher in studies with any risk of bias domain rated as “high” or “probably high” compared with studies with only a “low” or “probably low” risk of bias, and in studies not reporting the health outcome by International Statistical Classification of Diseases and Related Health Problems (ICD) code compared with the two studies reporting ICD codes. The quality of available evidence of the effect of any occupational exposure to solar UVR on melanoma incidence and mortality and on NMSC mortality was rated as “low”, and the quality of evidence for NMSC incidence was rated as “moderate”. The strength of the existing bodies of evidence reporting on occupational exposure to solar UVR was judged as “inadequate evidence for harmfulness” for melanoma mortality and NMSC mortality. For the health outcome of melanoma incidence, the strength of evidence was judged as “limited evidence for harmfulness”, that is, a positive relationship was observed between exposure and outcome where chance, bias and confounding cannot be ruled out with reasonable confidence. For the health outcome of NMSC incidence, the strength of evidence was judged as “sufficient evidence of harmfulness”, that is, a positive relationship is observed between exposure and outcome where chance, bias and confounding can be ruled out with reasonable confidence. The 2009 International Agency for Research on Cancer classification of solar UVR as a Group 1 carcinogen that causes cutaneous melanoma and NMSC is a compelling attribute for the strength of evidence on occupational exposure to solar UVR and skin cancer incidence. Producing estimates for the burden of NMSC attributable to occupational exposure to solar UVR appears evidence-based (while acknowledging the limitations of the bodies of evidence), and the pooled effect estimates can be used as input data for the WHO/ILO Joint Estimates

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group

<p>Abstract</p> <p>Background</p> <p>Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Several recent publications have noted an increasing trend in incidence over time. The international PPH collaboration was convened to explore the observed trends and to set out actions to address the factors identified.</p> <p>Methods</p> <p>We reviewed available data sources on the incidence of PPH over time in Australia, Belgium, Canada, France, the United Kingdom and the USA. Where information was available, the incidence of PPH was stratified by cause.</p> <p>Results</p> <p>We observed an increasing trend in PPH, using heterogeneous definitions, in Australia, Canada, the UK and the USA. The observed increase in PPH in Australia, Canada and the USA was limited solely to immediate/atonic PPH. We noted increasing rates of severe adverse outcomes due to hemorrhage in Australia, Canada, the UK and the USA.</p> <p>Conclusion</p> <p><it>Key Recommendations</it></p> <p indent="1">1. Future revisions of the International Classification of Diseases should include separate codes for atonic PPH and PPH immediately following childbirth that is due to other causes. Also, additional codes are required for placenta accreta/percreta/increta.</p> <p indent="1">2. Definitions of PPH should be unified; further research is required to investigate how definitions are applied in practice to the coding of data.</p> <p indent="1">3. Additional improvement in the collection of data concerning PPH is required, specifically including a measure of severity.</p> <p indent="1">4. Further research is required to determine whether an increased rate of reported PPH is also observed in other countries, and to further investigate potential risk factors including increased duration of labor, obesity and changes in second and third stage management practice.</p> <p indent="1">5. Training should be provided to all staff involved in maternity care concerning assessment of blood loss and the monitoring of women after childbirth. This is key to reducing the severity of PPH and preventing any adverse outcomes.</p> <p indent="1">6. Clinicians should be more vigilant given the possibility that the frequency and severity of PPH has in fact increased. This applies particularly to small hospitals with relatively few deliveries where management protocols may not be defined adequately and drugs or equipment may not be on hand to deal with unexpected severe PPH.</p

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue