"Float first and kick for your life": Psychophysiological basis for safety behaviour on accidental short-term cold water immersion

INTRODUCTION Accidental cold-water immersion (CWI) evokes the life threatening cold shock response (CSR) which increases the risk of drowning. Consequently, the safety behaviour selected is critical in determining survival; the present advice is to 'float first' and remain stationary (i.e. rest). We examined whether leg only exercise (i.e., treading water; 'CWI-Kick') immediately on CWI could reduce the symptoms of the CSR, offset the reduction in cerebral blood flow that is known to occur and reduce the CSR's symptoms of breathlessness. We also examined whether perceptual responses instinctive to accidental CWI were exacerbated by this alternative behaviour. We contrasted CWI-Kick to a 'CWI-Rest' condition and a thermoneutral control (35°C); 'TN-Rest'. METHOD Seventeen participants were tested (9 males, 8 females). All immersions were standardised; water temperature in cold conditions (i.e., 12°C) was matched ±/0.5°C within participant. Middle cerebral artery blood flow velocity (MCAv) and cardiorespiratory responses were measured along with thermal perception (sensation and comfort) and dyspnoea. Data were analysed using repeated measures ANOVA (alpha level of 0.05). RESULTS MCAv was significantly reduced in CWI-Rest (-6 (9)%; 1st minute of immersion) but was offset by leg only exercise immediately on cold water entry; CWI-Kick MCAv was never different to TN-Rest (-3 (16)% cf. 5 (4)%). All CWI cardiorespiratory and perceptual responses were different to TN-Rest but were not exacerbated by leg only exercise. DISCUSSION Treading water may aid survival by offsetting the reduction in brain blood flow velocity without changing the instinctive behavioural response (i.e. perceptions). "Float first - and kick for your life" would be a suitable amendment to the water safety advice

Intrinsic, Pro-Apoptotic Effects of IGFBP-3 on Breast Cancer Cells are Reversible: Involvement of PKA, Rho, and Ceramide

We established previously that IGFBP-3 could exert positive or negative effects on cell function depending upon the extracellular matrix composition and by interacting with integrin signaling. To elicit its pro-apoptotic effects IGFBP-3 bound to caveolin-1 and the beta 1 integrin receptor and increased their association culminating in MAPK activation. Disruption of these complexes or blocking the beta 1 integrin receptor reversed these intrinsic actions of IGFBP-3. In this study we have examined the signaling pathway between integrin receptor binding and MAPK activation that mediates the intrinsic, pro-apoptotic actions of IGFBP-3. We found on inhibiting protein kinase A (PKA), Rho associated kinase (ROCK), and ceramide, the accentuating effects of IGFBP-3 on apoptotic triggers were reversed, such that IGFBP-3 then conferred cell survival. We established that IGFBP-3 activated Rho, the upstream regulator of ROCK and that beta1 integrin and PKA were upstream of Rho activation, whereas the involvement of ceramide was downstream. The beta 1 integrin, PKA, Rho, and ceramide were all upstream of MAPK activation. These data highlight key components involved in the pro-apoptotic effects of IGFBP-3 and that inhibiting them leads to a reversal in the action of IGFBP-3

Realtime Emotional Reflective User Interface Based on Deep Convolutional Neural Networks and Generative Adversarial Networks

It is becoming increasingly apparent that a significant amount of the population suffers from mental health problems, such as stress, depression, and anxiety. These issues are a result of a vast range of factors, such as genetic conditions, social circumstances, and lifestyle influences. A key cause, or contributor, for many people is their work; poor mental state can be exacerbated by jobs and a person’s working environment. Additionally, as the information age continues to burgeon, people are increasingly sedentary in their working lives, spending more of their days seated, and less time moving around. It is a well-known fact that a decrease in physical activity is detrimental to mental well-being. Therefore, the need for innovative research and development to combat negativity early is required. Implementing solutions using Artificial Intelligence has great potential in this field of research. This work proposes a solution to this problem domain, utilising two concepts of Artificial Intelligence, namely, Convolutional Neural Networks and Generative Adversarial Networks. A CNN is trained to accurately predict when an individual is experiencing negative emotions, achieving a top accuracy of 80.38% with a loss of 0.42. A GAN is trained to synthesise images from an input domain that can be attributed to evoking position emotions. A Graphical User Interface is created to display the generated media to users in order to boost mood and reduce feelings of stress. The work demonstrates the capability for using Deep Learning to identify stress and negative mood, and the strategies that can be implemented to reduce them

Aircraft Cost Index and the Future of Carbon Emissions from Air Travel

Air travel accounts for 2% of global CO2 emissions and this proportion is set to grow in the future. There are currently no large scale solutions to drastically reduce the industry’s dependence on oil. Therefore, airlines are looking to use a basket of measures to reduce fuel consumption. Optimisation of the use of cost index (CI) could be a valuable addition to this. By balancing time-dependent costs with the cost of fuel, it controls the speed of the aircraft to achieve the most economic flight time. This has a direct impact on the CO2 emissions from the aircraft, with higher speeds resulting in higher fuel consumption. The aim of this study is to assess the impact that CI has on CO2 emissions for six different aircraft models on a flight-by-flight basis and to evaluate how the CI could be affected by future impacts on the industry for a representative aircraft. Results show that a range of representative CI values for different aircraft models exist and suggest that the maximum benefit for optimising CI values occurs for long range flights. The average saving in CO2 emissions is 1%. Results show that time-related costs have the greatest effect on the optimum CI values, particularly delay costs. On the fuel side of the equation it is notable that a carbon price resulting from the implementation of a market based mechanism has little impact on the optimum CI and only reduces CO2 emissions by 0.01% in this case. The largest savings in CO2 emissions result from the use of biofuels, with reductions of between 9% and 44% for 10% and 50% blends respectively. This study also highlights the need for further research into crew and maintenance costs, cumulative costs and delay induced by congestion and climate change events, as well as policy considerations to ensure that there is a reduction in CO2 emissions. The study concludes that CI should be seen as a valuable tool in both helping to reduce CO2 emissions, as well to assess the impact of future events on the industry

Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial.

Introduction Vasopressin stimulates cyst growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water intake could achieve a similar effect, necessitating a definitive large-scale trial of high water intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial. Methods and Analysis We describe the design of a single-centre, open label, prospective, randomised controlled trial. DRINK aims to enroll 50 ADPKD patients, over the age 16years with an eGFR≥20ml/min/1.73m2. Participants will be randomised 1:1 to high water (HW) intake based on an individualised water intake prescription, or to ad libitum(AW) water intake. The HW group will aim for a dilute urine (urine osmolality≤270mOsmo/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8week treatment period, and will be seen at week 0, 2,4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility endpoints are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of high water intake on measured (51Cr-EDTA) and estimated glomerular filtration rate, and ADPKD-related pain. Ethics and Dissemination Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer reviewed journals, and presented to patients via the PKD Charity. Trial Registration Details: NCT02933268 and ISCRTN1679495

Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial.

INTRODUCTION: Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water (HW) intake could achieve a similar effect, necessitating a definitive large-scale trial of HW intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial. METHODS AND ANALYSIS: We describe the design of a single-centre, open-label, prospective, randomised controlled trial. The "Determining feasibility of R andomisation to high vs. ad libitum water In take in Polycystic K idney Disease" (DRINK) trial aims to enrol 50 patients with ADPKD, over the age of 16 years with an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2. Participants will be randomised 1:1 to HW intake based on an individualised water intake prescription, or to ad libitum (AW) water intake. The HW group will aim for a dilute urine (urine osmolality ≤270 mOsm/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8-week treatment period, and will be seen at weeks 0, 2, 4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility end points are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of HW intake on measured (51Cr-EDTA) and eGFR and ADPKD-related pain. ETHICS AND DISSEMINATION: Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer-reviewed journals, and presented to patients via the PKD Charity. TRIAL REGISTRATION NUMBER: NCT02933268 and ISCRTN16794957

Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients with Cystic Fibrosis

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section