Patient Perspective on Convenience and Intensification of Insulin Treatment In Type 2 Diabetes In Italy

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Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes

OBJECTIVES: This study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes in 12 countries, diagnosed >6 months prior and receiving insulin for >3 months, were recruited through a representative online panel. Data were collected via online questionnaire and analyzed using a standard choice model for discrete choice experiment. RESULTS: A total of 3758 patients from North America (n=646), South America (n=1537), and Europe (n=1575) completed the study. Mean glycated hemoglobin (HbA1c) levels in North America, South America, and Europe were 63 mmol/mol (7.9%), 75 mmol/mol (9.0%), and 64 mmol/mol (8.0%), respectively. In the three regions, monthly willingness to pay was US$116, US$74, and US$92, respectively, for a 1$99, US$80, and US$104 for one less major hypoglycemic event per year; and US$64, US$37 and US$60 for a 3 kg weight decrease. To avoid preinjection preparation of insulin, the respective values were US$47, US$18, and US$37, and US$25, US$25, and US$24 for one less injection per day. Among respondents on basal-only insulin who had previously tried a more intensive regimen, reasons for switching back included difficulty in handling multiple injections and risk of hypoglycemic events. CONCLUSIONS: Reducing HbA1c, frequency of major hypoglycemic events and weight decrease were the highest valued outcomes in each region. The administrative burden of injections was also considered important

What supervisors and universities can do to enhance doctoral student experience (and how they can help themselves)

Over the past two decades, there has been a flurry of government papers and policy reports worldwide calling for increased number and diversity of doctoral researchers and a broadening of the curriculum to meet the developing needs of respective national 'knowledge-driven' economies. This has been followed by position papers and best practice examples of employability skills development in boundary-crossing doctoral programmes, especially in response to these initiatives. However, there is a disassociation between this ample literature expounding the new doctorate with its broader remit, inclusivity and production of 'industry-ready' graduates, and the comparatively sparse literature on the doctoral candidates' experiences of their programmes and career readiness. Within this review, we briefly outline international government initiatives and examples of the responses by Life Science and Biomedical doctoral programmes to address these various challenges. Further, we explore the recent literature on the lived experience of doctoral researchers by examining their perception of the recent changes to the research context to make recommendations for universities and supervisors on how to better support an ever more diverse doctoral population for a wide range of career opportunities. Examples of how doctoral researchers themselves can make the best of currently available opportunities are also provided

Transcriptomic Analysis Reveals Novel Mechanistic Insight into Murine Biological Responses to Multi-Walled Carbon Nanotubes in Lungs and Cultured Lung Epithelial Cells

There is great interest in substituting animal work with in vitro experimentation in human health risk assessment; however, there are only few comparisons of in vitro and in vivo biological responses to engineered nanomaterials. We used high-content genomics tools to compare in vivo pulmonary responses of multiwalled carbon nanotubes (MWCNT) to those in vitro in cultured lung epithelial cells (FE1) at the global transcriptomic level. Primary size, surface area and other properties of MWCNT- XNRI -7 (Mitsui7) were characterized using DLS, SEM and TEM. Mice were exposed via a single intratracheal instillation to 18, 54, or 162 μg of Mitsui7/mouse. FE1 cells were incubated with 12.5, 25 and 100 μg/ml of Mitsui7. Tissue and cell samples were collected at 24 hours post-exposure. DNA microarrays were employed to establish mechanistic differences and similarities between the two models. Microarray results were confirmed using gene-specific RT-qPCR. Bronchoalveolar lavage (BAL) fluid was assessed for indications of inflammation in vivo. A strong dose-dependent activation of acute phase and inflammation response was observed in mouse lungs reflective mainly of an inflammatory response as observed in BAL. In vitro, a wide variety of core cellular functions were affected including transcription, cell cycle, and cellular growth and proliferation. Oxidative stress, fibrosis and inflammation processes were altered in both models. Although there were similarities observed between the two models at the pathway-level, the specific genes altered under these pathways were different, suggesting that the underlying mechanisms of responses are different in cells in culture and the lung tissue. Our results suggest that careful consideration should be given in selecting relevant endpoints when substituting animal with in vitro testing

Ophthalmology

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9+/-12.3-82.1+/-4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8+/-21.4 mum in the Rotterdam Study I to 104.7+/-12.5 mum in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mum/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (beta = -0.36 mum/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mum; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mum; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mum; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mum; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mum/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mum; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities

Methylamine and other simple N-bearing species in the hot cores NGC 6334I MM1–3

In the search for the building blocks of life, nitrogen-bearing molecules are of particular interest since nitrogen-containing bonds are essential for the linking of amino acids and ultimately the formation of larger biological structures. The elusive molecule methylamine (CH$_3$NH$_2$) is thought to be a key pre-biotic species but has so far only been securely detected in the giant molecular cloud Sgr B2. We identify CH$_3$NH$_2$ and other simple nitrogen-bearing species towards three hot cores in NGC 6334I. Column density ratios are derived in order to investigate the relevance of the individual species as precursors of biotic molecules. Observations obtained with ALMA were used to study transitions of CH$_3$NH$_2$, CH$_2$NH, NH$_2$CHO, and the $^{13}$C- and $^{15}$N-methyl cyanide (CH$_3$CN) isotopologues. Column densities are derived for each species assuming LTE and excitation temperatures in the range 220-340 K for CH$_3$NH$_2$, 70-110 K for the CH$_3$CN isotopologues, and 120-215 K for NH$_2$CHO and CH$_2$NH. We report the first detections of CH$_3$NH$_2$ towards NGC 6334I with column density ratios with respect to CH$_3$OH of 5.9$\times$10$^{-3}$, 1.5$\times$10$^{-3}$, and 5.4$\times$10$^{-4}$ for the three hot cores MM1, MM2, and MM3, respectively. These values are slightly lower than the values derived for Sgr B2 but higher by more than order of magnitude as compared with the values derived for the low-mass protostar IRAS 16293-2422B. The detections of CH$_3$NH$_2$ in the hot cores of NGC 6334I hint that CH$_3$NH$_2$ is generally common in the interstellar medium, albeit high-sensitivity observations are essential for its detection. The good agreement between model predictions of CH$_3$NH$_2$ ratios and the observations towards NGC 6334I indicate a main formation pathway via radical recombination on grain surfaces.Comment: Accepted for publication in A&