Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue.

Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.

Online training improves medical students' ability to recognise when a person is dying: The ORaClES randomised controlled trial.

BACKGROUND: Recognising dying is a key clinical skill for doctors, yet there is little training. AIM: To assess the effectiveness of an online training resource designed to enhance medical students' ability to recognise dying. DESIGN: Online multicentre double-blind randomised controlled trial (NCT03360812). The training resource for the intervention group was developed from a group of expert palliative care doctors' weightings of various signs/symptoms to recognise dying. The control group received no training. SETTING/PARTICIPANTS: Participants were senior UK medical students. They reviewed 92 patient summaries and provided a probability of death within 72 hours (0% certain survival - 100% certain death) pre, post, and 2 weeks after the training. Primary outcome: (1) Mean Absolute Difference (MAD) score between participants' and the experts' scores, immediately post intervention. Secondary outcomes: (2) weight attributed to each factor, (3) learning effect and (4) level of expertise (Cochran-Weiss-Shanteau (CWS)). RESULTS: Out of 168 participants, 135 completed the trial (80%); 66 received the intervention (49%). After using the training resource, the intervention group had better agreement with the experts in their survival estimates (δMAD = -3.43, 95% CI -0.11 to -0.34, p = <0.001) and weighting of clinical factors. There was no learning effect of the MAD scores at the 2-week time point (δMAD = 1.50, 95% CI -0.87 to 3.86, p = 0.21). At the 2-week time point, the intervention group was statistically more expert in their decision-making versus controls (intervention CWS = 146.04 (SD 140.21), control CWS = 110.75 (SD 104.05); p = 0.01). CONCLUSION: The online training resource proved effective in altering the decision-making of medical students to agree more with expert decision-making.

Autonomous Deployment of Underwater Acoustic Monitoring Devices Using an Unmanned Aerial Vehicle: The Flying Hydrophone.

Unmanned aerial vehicles (UAV) are increasingly becoming a popular tool in the observation and study of marine mammals. However, the potential capabilities of these vehicles regarding autonomous operations are not being fully exploited for passive underwater acoustic monitoring in marine mammal research. This article presents results from the development of a UAV system equipped with an underwater acoustic recorder aimed at assisting with the monitoring of harbour porpoises in Special Areas of Conservation in the United Kingdom. The UAV is capable of autonomous navigation, persistent landing, take-off and automatic data acquisition at specified waypoints. The system architecture that enables autonomous UAV flight including waypoint planning and control is described. A bespoke lightweight underwater acoustic recorder (named the PorpDAQ) capable of transmitting the results of fast Fourier transforms (FFT) applied to incoming signals from a hydrophone was also designed. The system's operation is successfully validated with a combination of outdoor experiments and indoor simulations demonstrating different UAVs capable of autonomously navigating and landing at specific waypoints while recording data in an indoor tank. Results from the recorder suggest that lightweight, relatively low-cost systems can be used in place of heavier more expensive alternatives.

RiverCore: IoT Device for River Water Level Monitoring over Cellular Communications.

Flooding is one of the most frequent and costly natural disasters affecting mankind. However, implementing Internet of Things (IoT) technology to monitor river behavior may help mitigate or prevent future disasters. This article outlines the hardware development of an IoT system (RiverCore) and defines an application scenario in a specific hydrological region of the state of Colima (Mexico), highlighting the characteristics of data acquisition and data processing used. Both fixed position and moving drifter node systems are described along with web-based data acquisition platform developments integrated with IoT techniques to retrieve data through 3G cellular networks. The developed architecture uses the Message Queuing Telemetry Transport (MQTT) protocol, along with encryption and security mechanisms, to send real-time data packages from fixed nodes to a server that stores retrieved data in a non-relational database. From this, data can be accessed and displayed through different customizable queries and graphical representations, allowing future use in flood analysis and prediction systems. All of these features are presented along with graphical evidence of the deployment of the different devices and of several cellular communication and on-site data acquisition tests.

Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections.

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 µg/liter, 14 µg/liter, 25 µg/liter, and 153 µg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections.

Acoustical Direction Finding with Time-Modulated Arrays.

Time-Modulated Linear Arrays (TMLAs) offer useful efficiency savings over conventional phased arrays when applied in parameter estimation applications. The present paper considers the application of TMLAs to acoustic systems and proposes an algorithm for efficiently deriving the arrival angle of a signal. The proposed technique is applied in the frequency domain, where the signal and harmonic content is captured. Using a weighted average method on harmonic amplitudes and their respective main beam angles, it is possible to determine an estimate for the signal's direction of arrival. The method is demonstrated and evaluated using results from both numerical and practical implementations and performance data is provided. The use of Micro-Electromechanical Systems (MEMS) sensors allows time-modulation techniques to be applied at ultrasonic frequencies. Theoretical predictions for an array of five isotropic elements with half-wavelength spacing and 1000 data samples suggest an accuracy of ± 1 ∘ within an angular range of approximately ± 50 ∘ . In experiments of a 40 kHz five-element microphone array, a Direction of Arrival (DoA) estimation within ± 2 . 5 ∘ of the target signal is readily achieved inside a ± 45 ∘ range using a single switched input stage and a simple hardware setup.

Severe intraocular pressure response to periocular or intravitreal steroid treatment in Australia and New Zealand: data from the Australian and New Zealand Ophthalmic Surveillance Unit.

BACKGROUND: Increase in intraocular pressure is a recognized complication of corticosteroid treatment via intravitreal or periocular injections for treatment of a range of conditions including macular oedema and retinal neovascularization. DESIGN: This surveillance study was designed to determine the incidence and nature of severe intraocular pressure elevation as a complication of intravitreal or periocular corticosteroid injections in Australia and New Zealand. PARTICIPANTS: Seventeen cases meeting the defined criteria of severe intraocular pressure elevation, above 35 mmHg, following an intravitreal or periocular corticosteroid injection were included in the study. METHODS: Over an 18-month period, ophthalmologists were invited to report cases to the Australian and New Zealand Ophthalmic Surveillance Unit. After reporting, further demographic and clinical information was sought via a follow-up questionnaire. MAIN OUTCOME MEASURES: Intraocular pressure elevation above 35 mmHg. RESULTS: Follow-up questionnaires were received for 20 cases of 34 initially reported to the unit. Seventeen met the defined criteria. Triamcinolone acetonide was used in all 17 cases, with 16 delivered as a 4-mg intravitreal injection. There was an absence of identified underlying risk factors in the majority of cases with personal history of glaucoma in 2 of 17 cases. No cases reported a positive family history of glaucoma. Trabeculectomy was performed in 8 of 17 patients (47%) for intraocular pressure management. CONCLUSIONS: Severe intraocular pressure elevation following intravitreal or periocular corticosteroid injection can occur in the absence of risk factors such as personal and family history of glaucoma. The severe intraocular pressure elevation may ultimately require trabeculectomy.

Virtual reality reduces anxiety and pain in acute hospital palliative care: service evaluation.

OBJECTIVES: Virtual reality (VR) might improve symptom management, but there is limited evidence regarding VR in palliative care. We evaluated the feasibility of VR and impact on anxiety and pain for patients in a hospital palliative care consultation service. METHODS: Patients referred to a hospital specialist palliative care team, with anxiety or pain, were offered a VR intervention (a short audiovisual experience). Participants rated anxiety and pain on a 0-10 Likert severity scale pre intervention/post intervention and completed an evaluation form. Change in symptom scores was analysed by parametric statistics. RESULTS: 28 participants used VR a total of 42 times with no adverse events. Mean pain score reduced by 29% from 4.10 (SD=2.71) pre intervention to 2.93 (SD=2.45) post intervention (t(27)=5.150, p<0.001). Mean anxiety scores reduced by 40% from 4.43 (SD=2.56) to 2.65 (SD=2.24) (t(27)=5.058, p<0.001). Patients rated the experience on average 4.75/5 and all would recommend use to a friend. VR was described as absorbing and relaxing. CONCLUSION: VR may improve anxiety and pain and was acceptable in this setting. Large-scale evaluation will generate important data on feasibility and implementation.

The dynamic atmospheric and aeolian environment of Jezero crater, Mars.

Despite the importance of sand and dust to Mars geomorphology, weather, and exploration, the processes that move sand and that raise dust to maintain Mars' ubiquitous dust haze and to produce dust storms have not been well quantified in situ, with missions lacking either the necessary sensors or a sufficiently active aeolian environment. Perseverance rover's novel environmental sensors and Jezero crater's dusty environment remedy this. In Perseverance's first 216 sols, four convective vortices raised dust locally, while, on average, four passed the rover daily, over 25% of which were significantly dusty ("dust devils"). More rarely, dust lifting by nonvortex wind gusts was produced by daytime convection cells advected over the crater by strong regional daytime upslope winds, which also control aeolian surface features. One such event covered 10 times more area than the largest dust devil, suggesting that dust devils and wind gusts could raise equal amounts of dust under nonstorm conditions.

Endogenous endophthalmitis associated with intravenous drug abuse: seven-year experience at a tertiary referral center.

PURPOSE: Intravenous drug use (IVDU) is a known risk factor for endogenous endophthalmitis. Endogenous fungal endophthalmitis (EFE) is emerging as a common problem among this community. We describe the management and visual outcomes of acute IVDU-associated EFE. METHODS: A prospective consecutive case series of 19 patients presenting with presumed acute IVDU-associated EFE from 2001 to 2007 to the Royal Victorian Eye and Ear Hospital was included. All data were collected in a standardized manner. Outcome measures included visual acuity, microbial profiles, and vitrectomy rate. RESULTS: Nineteen cases of IVDU-associated EFE were identified. Eight of these (42%) were men, and the mean age was 32.7 years (SD ± 8.0 years). Presenting visual acuity ranged from 6/6 to perception of light, with 58% having a visual acuity of 6/48 or less at presentation. Thirteen (68.4%) were culture positive with all cultures identifying Candida species, and 52.7% underwent vitrectomy. Fifty percent of subjects overall achieved a final visual acuity of 6/18 or better. Men demonstrated improved visual acuity when compared with women (P = 0.04). Age had no effect on final acuity. CONCLUSION: Intravenous drug use is a significant risk factor for developing EFE. Good visual outcomes can be achieved with early treatment, often with intravitreal therapy alone.

High prevalence of older Australians with one or more joint replacements: estimating the population at risk for late complications of arthroplasty.

BACKGROUND: To provide an estimate of the population at risk for late complications of arthroplasty, we aimed to determine the prevalence of Australians living with one or more joint replacements. METHODS: Data included all arthroplasty procedures performed in Australia from 2003 to 2016 recorded by the Australian Orthopaedic Association National Joint Replacement Registry. The age- and gender-specific Australian population was obtained from the Australian Bureau of Statistics and used as denominator data. Survival data for each joint replacement, and of individuals, were used to estimate the arthroplasty prevalence. Analyses by age, gender and joint replacement site were undertaken. Prevalence estimates were augmented with procedural data captured before 2003 modelled with assumptions accounting for age and gender distributions, overall survival and arthroplasty revision rates. RESULTS: By the end of 2016, there were 824 769 Australians living with at least one joint replacement, representing 3.4% of the total population. The prevalence of joint replacement is increasing in all age groups, but was highest amongst older Australians, with an overall prevalence of 22.5%, and 13.3% in those aged >85 years and 65-84 years, respectively. The prevalence of people living with multiple joint replacements is increasing more rapidly than patients who have undergone only one joint replacement procedure. CONCLUSION: The prevalence of older Australians living with joint replacements is rapidly increasing, providing an estimate of the population-at-risk for late complications of arthroplasty including peri-prosthetic infection and fracture.

Avastin as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy: a prospective case series.

PURPOSE: Bevacizumab (Avastin) is a monoclonal antibody which targets all isoforms of vascular endothelial growth factor A. Its potent anti-angiogenic effects have been shown to cause regression of neovascularization in proliferative diabetic retinopathy. The aim of this study is to investigate the role of Avastin as an adjunct to vitrectomy in the management of severe diabetic eye disease. METHODS: Sixteen patients (18 eyes) with severe proliferative diabetic retinopathy were recruited into the study. All eyes underwent a single intravitreal injection of bevacizumab 1.25 mg in 0.05 mL prior to vitrectomy surgery for the management of tractional retinal detachment or vitreous haemorrhage due to severe proliferative diabetic retinopathy. RESULTS: At 3 months, seven eyes had visual acuities which were better than baseline, four were unchanged and seven were worse. At 6 months, 14 eyes had visual acuities better than baseline, one was unchanged and three were worse. Seven of the 18 eyes (38.8%) had postoperative rebleeds, six of which required surgical washout. CONCLUSION: Avastin improved the ease of the surgery in these complex eyes and the early results are encouraging. We have found it to be particularly useful in diabetic eyes with traction detachments of short duration in which there is still active neovascularization.

Burnout and career satisfaction among US oncologists.

PURPOSE: To evaluate the personal and professional characteristics associated with career satisfaction and burnout among US oncologists. METHODS: Between October 2012 and March 2013, the American Society of Clinical Oncology conducted a survey of US oncologists evaluating burnout and career satisfaction. The survey sample included equal numbers of men and women and represented all career stages. RESULTS: Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys (median age of respondents, 52 years; 49.6% women). Among the 1,117 oncologists (37.3% of overall sample) who completed full-length surveys, 377 (33.8%) were in academic practice (AP) and 482 (43.2%) in private practice (PP), with the remainder in other settings. Oncologists worked an average of 57.6 hours per week (AP, 58.6 hours per week; PP, 62.9 hours per week) and saw a mean of 52 outpatients per week. Overall, 484 oncologists (44.7%) were burned out on the emotional exhaustion and/or depersonalization domain of Maslach Burnout Inventory (AP, 45.9%; PP, 50.5%; P = .18). Hours per week devoted to direct patient care was the dominant professional predictor of burnout for both PP and AP oncologists on univariable and multivariable analyses. Although a majority of oncologists were satisfied with their career (82.5%) and specialty (80.4%) choices, both measures of career satisfaction were lower for those in PP relative to AP (all P < .006). CONCLUSION: Overall career satisfaction is high among US oncologists, albeit lower for those in PP relative to AP. Burnout rates among oncologists seem similar to those described in recent studies of US physicians in general. Those oncologists who devote the greatest amount of their professional time to patient care seem to be at greatest risk for burnout.

Elastic scattering spectroscopy for detection of cancer risk in Barrett's esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy.

Elastic scattering spectroscopy (ESS) may be used to detect high-grade dysplasia (HGD) or cancer in Barrett's esophagus (BE). When spectra are measured in vivo by a hand-held optical probe, variability among replicated spectra from the same site can hinder the development of a diagnostic model for cancer risk. An experiment was carried out on excised tissue to investigate how two potential sources of this variability, pressure and angle, influence spectral variability, and the results were compared with the variations observed in spectra collected in vivo from patients with Barrett's esophagus. A statistical method called error removal by orthogonal subtraction (EROS) was applied to model and remove this measurement variability, which accounted for 96.6% of the variation in the spectra, from the in vivo data. Its removal allowed the construction of a diagnostic model with specificity improved from 67% to 82% (with sensitivity fixed at 90%). The improvement was maintained in predictions on an independent in vivo data set. EROS works well as an effective pretreatment for Barrett's in vivo data by identifying measurement variability and ameliorating its effect. The procedure reduces the complexity and increases the accuracy and interpretability of the model for classification and detection of cancer risk in Barrett's esophagus.

Shedding light on plant competition: modelling the influence of plant morphology on light capture (and vice versa).

A plant's morphology is both strongly influenced by local light availability and, simultaneously, strongly influences this local light availability. This reciprocal relationship is complex, but lies at the heart of understanding plant growth and competition. Here, we develop a sub-individual-based simulation model, cast at the level of interacting plant components. The model explicitly simulates growth, development and competition for light at the level of leaves, branches, etc., located in 3D space. In this way, we are able to explore the manner in which the low-level processes governing plant growth and development give rise to individual-, cohort-, and community-level phenomena. In particular, we show that individual-level trade-offs between growing up and growing out arise naturally in the model, and robustly give rise to cohort-level phenomena such as self-thinning, and community processes such as the effect of ecological disturbance on the maintenance of biodiversity. We conclude with a note on our methodology and how to interpret the results of simulation models such as this one.

Quinolactacins revisited: from lactams to imide and beyond.

Chemical analysis of a solid phase fermentation of an Australian Penicillium citrinum strain has returned all known examples of a rare class of N-methyl quinolone lactams, quinolactacins A2 (1), B2 (2), C2 (3) and A1 (4), together with the new quinolactacins B1 (5), C1 (6), D1 (7) and D2 (8), and the novel derivatives quinolonimide (9) and quinolonic acid (10). Complete stereostructures were assigned to all these compounds by detailed spectroscopic analysis and chemical interconversion. Carefully controlled and monitored decomposition studies have confirmed that quinolactacins readily undergo C-3 epimerization and oxidation, and under appropriate conditions convert to quinolonimide and quinolonic acid. Mechanisms for key transformations are proposed. The decomposition studies suggested that only quinolactacins A2 (1) and B2 (2) are genuine natural products, with all other isolated compounds being decomposition artefacts. Quinolactacins C1 (6), C2 (3), and the racemic mixture of quinolactacins D1/D2 (8/7) all displayed notable cytotoxic activity.

Hepatitis C virus genotype and HIV coinfection affect cytokine mRNA levels in unstimulated PBMC but do not shift the T1/T2 balance.

Rapid progression of hepatitis C virus (HCV) disease in patients with HIV/HCV may reflect different cytokine responses and be influenced by HCV genotype. This is addressed by a study of patients with HIV/HCV coinfection and infection with HCV genotype 2 or 3 (2/3). They are compared with coinfected patients infected with genotype 1 and HCV monoinfected patients matched for HCV genotype. IFN-gamma, IL-10, IL-4 and IL-4delta2 mRNA were quantified by real-time PCR in unstimulated PBMC and after in vitro stimulation with HCV core or nonstructural 3/4A antigen. In unstimulated PBMC, levels of IFN-gamma and IL-4 mRNA were lowest in HIV/HCV genotype 1 patients, intermediate in HIV/HCV genotype 2/3 patients and highest in HCV genotype 2/3 patients. Neither HCV genotype nor HIV affected levels of IL-10 mRNA in unstimulated PBMC or IFN-gamma, IL-4 and IL-10 mRNA in PBMC stimulated with HCV antigens. Levels of IL-4 and IL-4delta2 mRNA correlated in mitogen-stimulated PBMC from all patient groups but both were low in HIV/HCV genotype 1 patients. Serum soluble CD30 levels (a putative marker of a T2 cytokine environment) did not differ between patient groups. The data do not suggest a shift in the T1/T2 balance driven by HIV coinfection or HCV genotype but either may affect IL-4 bioavailability.

Roquefortine E, a diketopiperazine from an Australian isolate of Gymnoascus reessii.

The new isoprenylated diketopiperazine roquefortine E (6) has been isolated from an Australian soil isolate of the ascomycete Gymnoascus reessii. The known fungal metabolite roquefortine C (1) was also recovered as the major antibacterial principle, and all structures were assigned by detailed spectroscopic analysis.