Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage

Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.- Background - Results -- Authentication of a preserved oral biofilm in calculus samples -- Dental calculus and plaque biofilm communities are distinct -- Health-associated communities of dental plaque and calculus are distinct -- Signatures of health and of disease are shared in modern and historic calculus samples -- Microbial community differences between health and disease in calculus are poorly resolved -- Absence of caries-specific microbial profiles in dental calculus -- Microbial co-exclusion patterns in plaque and calculus reflect biofilm maturity -- Microbial complexes in plaque and calculus -- Functional prediction in calculus is poorly predictive of health status -- Proteomic profiles of historic healthy site calculus -- Correlations between taxonomic, proteomic, and metabolomic profiles - Discussion - Conclusions - Materials and methods --Historic and modern calculus sample collection DNA extraction -- DNA library construction and high-throughput sequencing -- DNA sequence processing -- Genetic assessment of historic calculus sample preservation -- Genetic microbial taxonomic profiling -- Principal component analysis -- Assessment of differentially abundant taxa -- Sparse partial least squares-discriminant analysis -- Assessment of microbial co-exclusion patterns -- Gene functional categorization with SEED -- Proteomics -- Metabolomics -- Regularized canonical correlation analysi

Life after prostate cancer diagnosis: protocol for a UK-wide patient-reported outcomes study

Background: Prostate cancer and its treatment may impact physically, psychologically and socially; affecting the health-related quality of life of men and their partners/spouses. The Life After Prostate Cancer Diagnosis (LAPCD) study is a UK-wide patient-reported outcomes study which will generate information to improve the health and well-being of men with prostate cancer. Methods and analysis: Postal surveys will be sent to prostate cancer survivors (18–42 months postdiagnosis) in all 4 UK countries (n=∼70 000). Eligible men will be identified and/or verified through cancer registration systems. Men will be surveyed twice, 12 months apart, to explore changes in outcomes over time. Second, separate cohorts will be surveyed once and the design will include evaluation of the acceptability of online survey tools. A comprehensive patient-reported outcome measure has been developed using generic and specific instruments with proven psychometric properties and relevance in national and international studies. The outcome data will be linked with administrative health data (eg, treatment information from hospital data). To ensure detailed understanding of issues of importance, qualitative interviews will be undertaken with a sample of men who complete the survey across the UK (n=∼150) along with a small number of partners/spouses (n=∼30). Ethics and dissemination: The study has received the following approvals: Newcastle and North Tyneside 1 Research Ethics Committee (15/NE/0036), Health Research Authority Confidentiality Advisory Group (15/CAG/0110), NHS Scotland Public Benefit and Privacy Panel (0516-0364), Office of Research Ethics Northern Ireland (16/NI/0073) and NHS R&D approval from Wales, Scotland and Northern Ireland. Using traditional and innovative methods, the results will be made available to men and their partners/spouses, the funders, the NHS, social care, voluntary sector organisations and other researchers

Increased exhalation of hydrogen peroxide in healthy subjects following cigarette consumption

CONTEXT: Increased hydrogen peroxide has been described in the expired breath condensate (H2O2-E) of several lung conditions, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease and asthma. This technique has been advocated as being a simple method for documenting airway inflammation. OBJECTIVE: To evaluate H2O2-E in healthy cigarette smokers, and to determine the acute effects of the consumption of one cigarette on H2O2-E levels. TYPE OF STUDY: Prospective, controlled trial. SETTING: A pulmonary function laboratory in a University Hospital. PARTICIPANTS: Two groups of healthy volunteers: individuals who had never smoked (NS; n=10; 4 men; age = 30.6 ± 6.2 years) and current cigarette smokers (S; n=12; 7 men; age = 38.7 ± 9.8). None of the volunteers had respiratory symptoms and all showed normal spirometric tests. INTERVENTION: Expired air was collected from all volunteers through a face mask and a plastic collecting system leading into a flask with dry ice and pure ethanol. Samples from the group S were collected twice, before and half an hour after the combustion of one cigarette. MAIN MEASUREMENTS: Expired hydrogen peroxide using the Gallati and Pracht method. RESULTS: The S and NS groups showed comparable levels of H2O2-E at basal conditions [NS = 0.74 muM (DP 0.24) vs. S = 0.75 muM (DP 0.31)]. The smokers showed a significant increase in H2O2-E levels half an hour after the consumption of only one cigarette [0.75 muM (DP 0.31) vs. 0.95 muM (DP 0.22)]. CONCLUSION: The present results are consistent with the concept that smokers increase oxidative stress with elevated production of reactive oxygen species, contributing to the development of smoking-related disorders.CONTEXTO: Elevações do peróxido de hidrogênio exalado (H2O2-E) tem sido descritas em diversas doenças pulmonares tais como a síndrome do desconforto respiratório agudo, doença pulmonar obstrutiva crônica e asma. Essa técnica tem sido preconizada como um método simples capaz de refletir inflamação ao nível das vias aéreas. OBJETIVO: Avaliar os níveis de H2O2-E em indivíduos normais e determinar os efeitos agudos do consumo de um cigarro sobre seus valores. TIPO DE ESTUDO: Ensaio clínico, prospectivo, controlado. LOCAL: Laboratório de função pulmonar de um Hospital Universitário. PARTICIPANTES: Dois grupos de voluntários sadios: indivíduos que nunca fumaram [NS; n = 10; 4 homens; idade = 30,6 anos (DP 6,2)] e indivíduos fumantes atuais [S; n = 12; 7 homens; idade = 38,7 anos (DP 9,8)]. Todos os voluntários não apresentavam sintomas respiratórios e exibiam testes espirométricos dentro da normalidade. INTERVENÇÃO: Ar expirado foi coletado de todos os voluntários utilizando-se uma máscara facial e um sistema colocado em um frasco com gelo seco e etanol absoluto. Amostras do grupo S foram coletadas duas vezes, antes e meia hora após o consumo de um cigarro. VARIÁVEIS ESTUDADAS: Peróxido de hidrogênio expirado utilizando-se o método de Gallati e Pracht. RESULTADOS: Ambos os grupos mostraram níveis comparáveis de H2O2-E em condições basais [NS = 0,74 miM (DP 0,24) vs. S = 0,75 miM (DP 0,31)]. Os fumantes mostraram um aumento significante dos níveis de H2O2-E meia hora após o consumo de apenas um cigarro [0,75 miM (DP 0,31) vs. 0,95 miM (DP 0,22)]. CONCLUSÃO: Os resultados obtidos estão de acordo com o conceito de que o consumo de cigarros aumenta o estresse oxidativo com produção elevada de espécies reativas do oxigênio (ROS) contribuindo para o desenvolvimento de doenças relacionadas ao tabagismo.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Pulmonary DivisionUniversity of São Paulo Medical School of Ribeirão Preto Department of MedicineUNIFESP, EPM, Pulmonary DivisionSciEL

Is it feasible to deliver a complex intervention to improve the outcome of falls in people with dementia? A protocol for the DIFRID feasibility study

Background: People with dementia (PWD) experience ten times as many incident falls as people without dementia. Little is known about how best to deliver services to people with dementia following a fall. We used an integrated, mixed-methods approach to develop a new intervention which combines theory generated via a realist synthesis and data on current provision and pathways, gathered through a prospective observational study as well as qualitative interviews, focus groups, and ethnographic observation. This intervention is to be tested in a feasibility study in the UK National Health Service. Methods: People living with dementia in one of three geographical areas will be eligible for the study if they experience a fall requiring healthcare attention and have an informal carer. Potential participants will be identified by community services (primary care, paramedics, telecare), secondary care (ED; facilitated discharge services; rehabilitation outreach teams) and research case registers. Participants will receive a complex multidisciplinary intervention focused on their goals and interests for up to 12 weeks. The intervention will be delivered by occupational therapists, physiotherapists and rehabilitation support workers. Feasibility outcomes will include recruitment and retention, suitability and acceptability of outcome measures and acceptability, feasibility and fidelity of intervention components. PWD outcome measures will include number of falls, Montreal Cognitive Assessment (MOCA), European Quality of Life Instrument (EQ-5D-5L), Quality of Life–Alzheimer’s Disease Scale (QOL-AD), Modified Falls Efficacy Scale (MFES) and Goal Attainment Scaling (GAS). PWD outcome measures completed by an informal carer will include Disability Assessment for Dementia (DAD), EQ-5D-5L Proxy, QoL-AD Proxy and a Health Utilisation Questionnaire (HUQ), The carer outcome measure will be the Zarit Burden Interview (ZBI). An embedded process evaluation will explore barriers and facilitators to recruitment and intervention delivery. Discussion: The study results will inform whether and how a larger multicentre RCT should be undertaken. A full RCT would have the potential to show how outcomes can be improved for people with dementia who have fallen. Ethics and dissemination: The National Research Ethics Service Committee Newcastle and North Tyneside 2 approved the feasibility study. Trial registration: International Standard Randomised Controlled Trial Registry Registration number: ISRCTN41760734 Date of registration: 16/11/201

Study on Wideband THz Backward Wave Oscillator Driven by Pseudospark-Sourced Sheet Electron Beam

A backward wave oscillator (BWO) based on a double-staggered grating (DSG) slow wave structure (SWS) is investigated as a high-power wideband terahertz (THz) source, driven by a sheet electron beam emitting from a pseudospark plasma cathode. First, the DSG SWS is optimized in simulation to have a suitable dispersion characteristic. Then, the BWO with a wideband output structure consisting of a tapered section of DSG and an L-shaped connector is modeled under an operating voltage of 24-38 kV and a current density of 2- 5\times 10 {{7}} A/m 2 (beam current of 1.5-3.8 A). A maximum power of 3.9 kW is obtained, and a wide bandwidth of over 38 GHz (343-381 GHz) is achieved. The impact of fabricating errors of the SWS on the performance of the BWO is analyzed in simulation. The effects of the plasma in the interaction space on the BWO performance are also analyzed, showing that the plasma causes an increase in the oscillation frequency by 1.0-1.2

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Funded by Asthma UK grant number 09/ 36

An evidence-based framework for predicting the impact of differing autotroph-heterotroph thermal sensitivities on consumer-prey dynamics

Increased temperature accelerates vital rates, influencing microbial population and wider ecosystem dynamics, for example, the predicted increases in cyanobacterial blooms associated with global warming. However, heterotrophic and mixotrophic protists, which are dominant grazers of microalgae, may be more thermally sensitive than autotrophs, and thus prey could be suppressed as temperature rises. Theoretical and meta-analyses have begun to address this issue, but an appropriate framework linking experimental data with theory is lacking. Using ecophysiological data to develop a novel model structure, we provide the first validation of this thermal sensitivity hypothesis: increased temperature improves the consumer’s ability to control the autotrophic prey. Specifically, the model accounts for temperature effects on auto- and mixotrophs and ingestion, growth and mortality rates, using an ecologically and economically important system (cyanobacteria grazed by a mixotrophic flagellate). Once established, we show the model to be a good predictor of temperature impacts on consumer–prey dynamics by comparing simulations with microcosm observations. Then, through simulations, we indicate our conclusions remain valid, even with large changes in bottom-up factors (prey growth and carrying capacity). In conclusion, we show that rising temperature could, counterintuitively, reduce the propensity for microalgal blooms to occur and, critically, provide a novel model framework for needed, continued assessment

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta