A novel oral syringe for dosing and administration of multiparticulate formulations : acceptability study in preschool and school children

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimised with a “standard” paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (Sympfiny™, HS Design, Morristown, NJ, USA) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4–12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4–12 years

Exposure of U.S. National Parks to land use and climate change 1900-2100

Many protected areas may not be adequately safeguarding biodiversity from human activities on surrounding lands and global change. The magnitude of such change agents and the sensitivity of ecosystems to these agents vary among protected areas. Thus, there is a need to assess vulnerability across networks of protected areas to determine those most at risk and to lay the basis for developing effective adaptation strategies. We conducted an assessment of exposure of U.S. National Parks to climate and land use change and consequences for vegetation communities. We first defined park protected-area centered ecosystems (PACEs) based on ecological principles. We then drew on existing land use, invasive species, climate, and biome data sets and models to quantify exposure of PACEs from 1900 through 2100. Most PACEs experienced substantial change over the 20th century (.740% average increase in housing density since 1940, 13% of vascular plants are presently nonnative, temperature increase of 18C/100 yr since 1895 in 80% of PACEs), and projections suggest that many of these trends will continue at similar or increasingly greater rates (255% increase in housing density by 2100, temperature increase of 2.58–4.58C/100 yr, 30% of PACE areas may lose their current biomes by 2030). In the coming century, housing densities are projected to increase in PACEs at about 82% of the rate of since 1940. The rate of climate warming in the coming century is projected to be 2.5–5.8 times higher than that measured in the past century. Underlying these averages, exposure of individual park PACEs to change agents differ in important ways. For example, parks such as Great Smoky Mountains exhibit high land use and low climate exposure, others such as Great Sand Dunes exhibit low land use and high climate exposure, and a few such as Point Reyes exhibit high exposure on both axes. The cumulative and synergistic effects of such changes in land use, invasives, and climate are expected to dramatically impact ecosystem function and biodiversity in national parks. These results are foundational to developing effective adaptation strategies and suggest policies to better safeguard parks under broad-scale environmental change

A regime view of the North Atlantic Oscillation and its response to anthropogenic forcing

The distribution of the daily wintertime North Atlantic Oscillation (NAO) index in the 40-yr ECMWF Re-Analysis (ERA-40) is significantly negatively skewed. Dynamical and statistical analyses both suggest that this skewness reflects the presence of two distinct regimes—referred to as “Greenland blocking” and “subpolar jet.” Changes in both the relative occurrence and in the structure of the regimes are shown to contribute to the long-term NAO trend over the ERA-40 period. This is contrasted with the simulation of the NAO in 100-yr control and doubled CO2 integrations of the third climate configuration of the Met Office Unified Model (HadCM3). The model has clear deficiencies in its simulation of the NAO in the control run, so its predictions of future behavior must be treated with caution. However, the subpolar jet regime does become more dominant under anthropogenic forcing and, while this change is small it is clearly statistically significant and does represent a real change in the nature of NAO variability in the model

TraDIS-Xpress: a high-resolution whole-genome assay identifies novel mechanisms of triclosan action and resistance

Understanding the genetic basis for a phenotype is a central goal in biological research. Much has been learnt about bacterial genomes by creating large mutant libraries and looking for conditionally important genes. However, current genome-wide methods are largely unable to assay essential genes which are not amenable to disruption. To overcome this limitation, we developed a new version of “TraDIS” (transposon directed insertion-site sequencing) that we term “TraDIS-Xpress” that combines an inducible promoter into the transposon cassette. This allows controlled overexpression and repression of all genes owing to saturation of inserts adjacent to all open reading frames as well as conventional inactivation. We applied TraDIS-Xpress to identify responses to the biocide triclosan across a range of concentrations. Triclosan is endemic in modern life, but there is uncertainty about its mode of action with a concentration-dependent switch from bacteriostatic to bactericidal action unexplained. Our results show a concentration-dependent response to triclosan with different genes important in survival between static and cidal exposures. These genes include those previously reported to have a role in triclosan resistance as well as a new set of genes, including essential genes. Novel genes identified as being sensitive to triclosan exposure include those involved in barrier function, small molecule uptake, and integrity of transcription and translation. We anticipate the approach we show here, by allowing comparisons across multiple experimental conditions of TraDIS data, and including essential genes, will be a starting point for future work examining how different drug conditions impact bacterial survival mechanisms

Performativity, fabrication and trust: exploring computer-mediated moderation

Based on research conducted in an English secondary school, this paper explores computer mediated moderation as a performative tool. The Module Assessment Meeting (MAM) was the moderation approach under investigation. I mobilise ethnographic data generated by a key informant, and triangulated with that from other actors in the setting, in order to examine some of the meanings underpinning moderation within a performative environment. Drawing on the work of Ball (2003), Lyotard (1979) and Foucault (1977, 1979), I argue that in this particular case performativity has become entrenched in teachers’ day-to-day practices, and not only affects those practices but also teachers’ sense of self. I suggest that MAM represented performative and fabricated conditions and (re)defined what the key participant experienced as a vital constituent of her educational identities - trust. From examining the case in point, I hope to have illustrated for those interested in teachers’ work some of the implications of the interface between technology and performativity

The Relationship between Mammography and a Multi-factor Behavioral Index

Objective: In this study, we sought to determine whether a multi-factor behavioral index predicts mammography screening in US women. Methods: Women aged 50-75 years were enrolled in an intervention study and provided their vegetable intake, physical activity (PA), smoking, body mass index (BMI), and alcohol intake. Each factor was scored from 0 (least healthy) to 4 (most healthy) then summed to form a multi-factor behavioral index (ranging from 0-20). Selfreport and medical records were used to determine mammography screening 6-months postintervention. Logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association with 6-month mammography. Results: The mean score for the multi-factor index was 11.8. An increased index score marginally predicted mammography adherence [OR = 1.05 (0.99-1.11)], with a stronger association among women receiving a doctor’s recommendation for mammography [OR = 1.12 (1.04-1.20)]. Of the independent behavioral factors, high PA [OR = 1.13 (0.99-1.30), p = .075] and low BMI [OR = 1.25 (1.04-1.51), p = .017] were marginal and significant predictors of mammography, respectively. Conclusion: Women who engaged in a healthier behavioral lifestyle were more likely to utilize mammography screening, especially if they received a physician recommendation. Physicians should encourage mammography screening as part of a healthy behavioral lifestyle

Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): protocol for a randomised controlled trial.

BACKGROUND: Self-monitoring of hypertension is associated with lower systolic blood pressure (SBP). However, evidence for the use of self-monitoring to titrate antihypertensive medication by physicians is equivocal. Furthermore, there is some evidence for the efficacy of telemonitoring in the management of hypertension but it is not clear what this adds over and above self-monitoring. This trial aims to evaluate whether GP led antihypertensive titration using self-monitoring results in lower SBP compared to usual care and whether telemonitoring adds anything to self-monitoring alone. METHODS/DESIGN: This will be a pragmatic primary care based, unblinded, randomised controlled trial of self-monitoring of BP with or without telemonitoring compared to usual care. Eligible patients will have poorly controlled hypertension (>140/90 mmHg) and will be recruited from primary care. Participants will be individually randomised to either usual care, self-monitoring alone, or self-monitoring with telemonitoring. The primary outcome of the trial will be difference in clinic SBP between intervention and control groups at 12 months adjusted for baseline SBP, gender, BP target and practice. At least 1110 patients will be sufficient to detect a difference in SBP between self-monitoring with or without telemonitoring and usual care of 5 mmHg with 90% power with an adjusted alpha of 0.017 (2-sided) to adjust for all three pairwise comparisons. Other outcomes will include adherence of anti-hypertensive medication, lifestyle behaviours, health-related quality of life, and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative sub study will gain insights into the views, experiences and decision making processes of patients and health care professionals focusing on the acceptability of self-monitoring and telemonitoring in the routine management of hypertension. DISCUSSION: The results of the trial will be directly applicable to primary care in the UK. If successful, self-monitoring of BP in people with hypertension would be applicable to hundreds of thousands of individuals in the UK. TRIAL REGISTRATION: ISRCTN 83571366 . Registered 17 July 2014.The trial is funded by an NIHR Programme grant, and by an NIHR Professorship awarded to Prof RJ McManus, the Chief Investigator. Omron have provided the blood pressure self-monitoring equipment via an unrestricted grant. Service support costs are administered through the NIHR Clinical Research Network: West Midlands. Professors Hobbs and Professor Farmer are NIHR Senior Investigators. This article presents independent research commissioned by the National Institute for Health Research (NIHR) under a Programme Grant for Applied Research (RP-PG-1209-10051)

A Randomized Trial to Compare a Tailored Web-Based Intervention and Tailored Phone Counseling to Usual Care for Increasing Colorectal Cancer Screening

Background: Colorectal cancer mortality could be decreased with risk-appropriate cancer screening. We examined the efficacy of three tailored interventions compared with usual care for increasing screening adherence. Methods: Women (n = 1,196) ages 51 to 74, from primary care networks and nonadherent to colorectal cancer guidelines, were randomized to (1) usual care, (2) tailored Web intervention, (3) tailored phone intervention, or (4) tailored Web + phone intervention. Average-risk women could select either stool test or colonoscopy, whereas women considered at higher than average risk received an intervention that supported colonoscopy. Outcome data were collected at 6 months by self-report, followed by medical record confirmation (attrition of 23%). Stage of change for colorectal cancer screening (precontemplation or contemplation) was assessed at baseline and 6 months. Results: The phone (41.7%, P < 0.0001) and combined Web + phone (35.8%, P < 0.001) interventions significantly increased colorectal cancer screening by stool test compared with usual care (11.1%), with ORs ranging from 5.4 to 6.8 in models adjusted for covariates. Colonoscopy completion did not differ between groups except that phone significantly increased colonoscopy completion compared with usual care for participants in the highest tertile of self-reported fear of cancer. Conclusions: A tailored phone with or without a Web component significantly increased colorectal cancer screening compared with usual care, primarily through stool testing, and phone significantly increased colonoscopy compared with usual care but only among those with the highest levels of baseline fear. Impact: This study supports tailored phone counseling with or without a Web program for increasing colorectal cancer screening in average-risk women

Association between pre-diagnostic leukocyte mitochondrial DNA copy number and survival among colorectal cancer patients

Background Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colorectal cancer (CRC) diagnosis and CRC prognosis, findings have been inconsistent, and no study has specifically investigated the association of pre-diagnostic mtDNAcn with CRC survival. Methods We examined the association of pre-diagnostic leukocyte mtDNAcn (measured by qPCR) with overall and CRC-specific survival among 587 patients in Nurses’ Health Study and Health Professionals Follow-Up Study. Cox models were constructed to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Results During a mean follow-up of 10.5 years, 395 deaths were identified; 180 were due to CRC. Overall, we did not observe significant associations between mtDNAcn and either overall or CRC-specific survival among all cases or by cancer location, grade, or stage. In an exploratory stratified analysis, a suggestive inverse association of mtDNAcn and overall death risk appeared among current smokers [HR (95 % CI) for 1 SD decrease in mtDNAcn = 1.50 (0.98, 2.32), P-trend = 0.06]. Reduced mtDNAcn and lower CRC-specific death risk was observed among patients aged ≤ 70.5 at diagnosis [HR (95 % CI) for 1 SD decrease of mtDNAcn = 0.71 (0.52, 0.97), P-trend = 0.03], ≤ 5 years from blood collection to diagnosis [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.65 (0.44, 0.96), P-trend = 0.03] and those consuming a low-inflammatory diet [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.61 (0.42, 0.88), P-trend = 0.009]. Conclusion no significant associations between pre-diagnostic leukocyte mtDNAcn and either overall or CRC-specific survival appeared but exploratory analysis identified potential sub-group associations