Positive pressure drug releasing device

A positive pressure long-term drug delivery device particularly useful for the intravaginal or intrauterine release of a drug capable of passing through a diffusion membrane and being absorbed by the vaginal or uterine epithelium. The device includes a tubular casing having a plunger urged by a compression spring to create a continuous positive pressure on a drug in liquid form within the chamber of the casing, a supported membrane at one end of the casing through which such drug diffuses at a predetermined rate, and resilient elements at the opposite end of the casing for facilitating retention of the device throughout the term of administration of the drug

Impact of high water pressure on oil generation and maturation in Kimmeridge Clay and Monterey source rocks: implications for petroleum retention and gas generation in shale gas systems

This study presents results for pyrolysis experiments conducted on immature Type II and IIs source rocks (Kimmeridge Clay, Dorset UK, and Monterey shale, California, USA respectively) to investigate the impact of high water pressure on source rock maturation and petroleum (oil and gas) generation. Using a 25 ml Hastalloy vessel, the source rocks were pyrolysed at low (180 and 245 bar) and high (500, 700 and 900 bar) water pressure hydrous conditions at 350 °C and 380 °C for between 6 and 24 h. For the Kimmeridge Clay (KCF) at 350 °C, Rock Eval HI of the pyrolysed rock residues were 30–44 mg/g higher between 6 h and 12 h at 900 bar than at 180 bar. Also at 350 °C for 24 h the gas, expelled oil, and vitrinite reflectance (VR) were all reduced by 46%, 61%, and 0.25% Ro respectively at 900 bar compared with 180 bar. At 380 °C the retardation effect of pressure on the KCF was less significant for gas generation. However, oil yield and VR were reduced by 47% and 0.3% Ro respectively, and Rock Eval HI was also higher by 28 mg/g at 900 bar compared with 245 bar at 12 h. The huge decrease in gas and oil yields and the VR observed with an increase in water pressure at 350 °C for 24 h and 380 °C for 12 h (maximum oil generation) were also observed for all other times and temperatures investigated for the KCF and the Monterey shale. This shows that high water pressure significantly retards petroleum generation and source rock maturation. The retardation of oil generation and expulsion resulted in significant amounts of bitumen and oil being retained in the rocks pyrolysed at high pressures, suggesting that pressure is a possible mechanism for retaining petroleum (bitumen and oil) in source rocks. This retention of petroleum within the rock provides a mechanism for oil-prone source rocks to become potential shale gas reservoirs. The implications from this study are that in geological basins, pressure, temperature and time will all exert significant control on the extent of petroleum generation and source rock maturation for Type II source rocks, and that the petroleum retained in the rocks at high pressures may explain in part why oil-prone source rocks contain the most prolific shale gas resources

Use of electrochemical sensors for measurement of air pollution: correcting interference response and validating measurements

The environments in which we live, work, and play are subject to enormous variability in air pollutant concentrations. To adequately characterize air quality (AQ), measurements must be fast (real time), scalable, and reliable (with known accuracy, precision, and stability over time). Lower-cost air-quality-sensor technologies offer new opportunities for fast and distributed measurements, but a persistent characterization gap remains when it comes to evaluating sensor performance under realistic environmental sampling conditions. This limits our ability to inform the public about pollution sources and inspire policy makers to address environmental justice issues related to air quality. In this paper, initial results obtained with a recently developed lower-cost air-quality-sensor system are reported. In this project, data were acquired with the ARISense integrated sensor package over a 4.5-month time interval during which the sensor system was co-located with a state-operated (Massachusetts, USA) air quality monitoring station equipped with reference instrumentation measuring the same pollutant species. This paper focuses on validating electrochemical (EC) sensor measurements of CO, NO, NO2, and O3 at an urban neighborhood site with pollutant concentration ranges (parts per billion by volume, ppb; 5 min averages, ±1σ): [CO]  =  231 ± 116 ppb (spanning 84–1706 ppb), [NO]  =  6.1 ± 11.5 ppb (spanning 0–209 ppb), [NO2]  =  11.7 ± 8.3 ppb (spanning 0–71 ppb), and [O3]  =  23.2 ± 12.5 ppb (spanning 0–99 ppb). Through the use of high-dimensional model representation (HDMR), we show that interference effects derived from the variable ambient gas concentration mix and changing environmental conditions over three seasons (sensor flow-cell temperature  =  23.4 ± 8.5 °C, spanning 4.1 to 45.2 °C; and relative humidity  =  50.1 ± 15.3 %, spanning 9.8–79.9 %) can be effectively modeled for the Alphasense CO-B4, NO-B4, NO2-B43F, and Ox-B421 sensors, yielding (5 min average) root mean square errors (RMSE) of 39.2, 4.52, 4.56, and 9.71 ppb, respectively. Our results substantiate the potential for distributed air pollution measurements that could be enabled with these sensors

Discovery of Western European R1b1a2 Y Chromosome Variants in 1000 Genomes Project Data: An Online Community Approach

The authors have used an online community approach, and tools that were readily available via the Internet, to discover genealogically and therefore phylogenetically relevant Y-chromosome polymorphisms within core haplogroup R1b1a2-L11/S127 (rs9786076). Presented here is the analysis of 135 unrelated L11 derived samples from the 1000 Genomes Project. We were able to discover new variants and build a much more complex phylogenetic relationship for L11 sub-clades. Many of the variants were further validated using PCR amplification and Sanger sequencing. The identification of these new variants will help further the understanding of population history including patrilineal migrations in Western and Central Europe where R1b1a2 is the most frequent haplogroup. The fine-grained phylogenetic tree we present here will also help to refine historical genetic dating studies. Our findings demonstrate the power of citizen science for analysis of whole genome sequence data

"I am becoming more and more like my eldest brother!": the relationship between older siblings, adolescent gambling severity, and the attenuating role of parents in a large-scale nationally representative survey study

The present study examined the association between having older siblings who gamble and adolescent at-risk/problem gambling and how parents (i.e., parental knowledge of their whereabouts) and peers might moderate such effects. Data were drawn from the ESPAD®Italia2012 survey (European School Survey Project on Alcohol and Other Drugs) comprising a nationally representative Italian sample of adolescents. The analysis was carried out on a subsample of 10,063 Italian students aged 15–19 years (average age = 17.10; 55 % girls) who had at least one older sibling and who had gambled at some point in their lives. Respondents’ problem gambling severity, older gambler sibling, gambler peers, parental knowledge, and socio-demographic characteristics were individually assessed. Multinomial logistic regression analyses including two- and three-way interactions were conducted. The odds of being an at-risk/problem gambler were higher among high school students with older siblings that gambled and those with peers who gambled. Higher parental knowledge (of who the adolescent was with and where they were in their leisure time) was associated with lower rates of at-risk/problem gambling. There was also an interaction between gamblers with older siblings and parental knowledge. The combination of having siblings who gambled and a greater level of parental knowledge was associated with lower levels of problem gambling. The present study confirmed the occurrence of social risk processes (older siblings and peers who gambled) and demonstrated that gambling among older siblings and peers represents an important contextual factor for increased at-risk/problem gambling. However, parental knowledge appears to be sufficient to counterbalance the influence of older siblings

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment