Moving forward to address key unanswered questions on targeting PD-1/PD-L1 in cancer: limitations in preclinical models and the need to incorporate human modifying factors.

The tremendous clinical success of immune checkpoint inhibition (ICI), particularly targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1/2 (PD-L1/2) pathway, has resulted in application to multiple cancers, as a monotherapy and as a companion to both conventional and novel agents. Despite this, the precise mechanisms underlying the anti-tumor effects of PD-1/PD-L1 blockade remain unclear. Emphasis has centered on its reversal of tumor-specific CD8+ T-cell exhaustion, although many cell types and processes are likely impacted. Due to the complex and pervasive roles of PD-1/PD-L1 on T-cell biology, including on initial T-cell priming, PD-1 blockade likely affects all aspects of T- cell responses, and these other effects may be even more critical for durable anti-tumor responses. Delineating these complex interactions necessitates in vivo modeling. By far, the healthy, young and inbred laboratory mouse, transplanted with an extensively cultured tumor cell line, has been the predominant preclinical model used to assess potential therapeutic efficacies. However, these mouse models often do not adequately reflect the tumor progression and cellular and genetic heterogeneity found within human cancers. Furthermore, laboratory mice also present with a vastly restricted immune profile compared to humans. This commentary discusses some of the critical questions that need to be addressed to optimize the use of ICI as well as caveats and limitations for consideration when extrapolating preclinical mouse data to the human cancer scenario

An International Comparison of Health Care Expenditure Determinants

In this paper, we estimate a health care demand function for 18 OECD countries for the period 1972-1995. We consider a demand side approach where health expenditure depend on per capita GDP and the relative price of health care. We use panel data unit root and stationarity tests to characterize our data. Then, we test cointegration between our variables with Kao[16] panel data cointegration tests. As we accept cointegration, we compare different estimators (OLS, FMOLS, DOLS). Results give conflicting evidence for the value of health expenditure income elasticity. The least biased estimator gives a value that exceeds unity.Cointegration, Health Expenditure, OECD, Panel test

The European Regional Convergence Process, 1980-1995: Do Spatial Regimes and Spatial Dependence Matter?

We show in this paper that spatial dependence and spatial heterogeneity matter in the estimation of the b-convergence process among 138 European regions over the 1980-1995 period. Using spatial econometrics tools, we detect both spatial dependence and spatial heterogeneity in the form of structural instability across spatial convergence clubs. The estimation of the appropriate spatial regimes spatial error model shows that the convergence process is different across regimes. We also estimate a strongly significant spatial spillover effect: the average growth rate of per capita GDP of a given region is positively affected by the average growth rate of neighboring regions.convergence, club convergence, spatial econometrics, European regions, spatial regimes, spatial autocorrelation

Prospectus Elements: Increasing Pediatric Immunization Rates

There has been a recent outbreak of Measles and the majority who contracted the disease were unvaccinated (CDC, 2015). An increase in pertussis cases from 2013 to 2014 have occurred as well from 28,639 cases to 32,971 in 2014 (CDC, 2015). This is endangering the community, and putting infants and the younger generation at risk. Increasing immunization rates for patients to be fully immunized has become crucial. Being fully immunized not only reduces their chances of getting these diseases, but also helps the rest of the population who are too young to get these vaccines (Daly, Matthew F. & Glanz, Jason M., 2011. By reaching out to patients through calls and letters, we were able to make them aware of the importance of being fully immunized and to bring their child in for immunization updates. Running reports and ensuring immunization rates do not fall below 80% for the clinic improves the clinic’s credibility, increases funding to increase staff and reach out to a bigger patient population, and most importantly keeps the community and the patients safe and healthy against preventative diseases. While it is important for those to be fully vaccinated for themselves, it is just as critical for other individuals surrounding them to be immunized as well. Increasing immunization rates and awareness can decrease disease outbreak all over the world and prevent unnecessary deaths and societal costs associated with these preventable diseases. Though the project did not meet its goal of 80% of patients between 23-35 months being fully immunized, the numbers show that with certain adjustments to the project the goal can be achieved since the percentage fell within the 71-74%. References Center For Disease Control And Prevention (CDC). (2015). CDC Vaccine Price List. Retrieved from http://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/ Center For Disease Control And Prevention (CDC). (2015). Measles Cases and Outbreaks. Retrieved from: http://www.cdc.gov/measles/cases-outbreaks.html Daly, Matthew F. & Glanz, Jason M. (2011). Straight Talk about Vaccination. The Science of Health. Retrieved from: http://www.scientificamerican.com/article/straight-talk-about-vaccination/?page=

Yield stress and elasticity influence on surface tension measurements

We have performed surface tension measurements on carbopol gels of different concentrations and yield stresses. Our setup, based on the force exerted by a capillary bridge on two parallel plates, allows to measure an effective surface tension of the complex fluid and to investigate the influence of flow history. More precisely the effective surface tension measured after stretching the bridge is always higher than after compressing it. The difference between the two values is due to the existence of a yield stress in the fluid. The experimental observations are successfully reproduced with a simple elasto-plastic model. The shape of successive stretching-compression cycles can be described by taking into account the yield stress and the elasticity of the gel. We show that the surface tension $\gamma_{LV}$ of yield stress fluids is the mean of the effective surface tension values only if the elastic modulus is high compared to the yield stress. This work highlights that thermodynamical quantities measurements are challenged by the fluid out-of-equilibrium state implied by jamming, even at small scales where the shape of the bridge is driven by surface energy. Therefore setups allowing deformation in opposite directions are relevant for measurements on yield stress fluids.Comment: 12 pages, 16 figures in Soft Matter 201

Influence of Lysine-Based Biomaterials on Fibroblast to Myofibroblast Differentiation

Fibrous encapsulation occurs as a result of implantation of devices such as pacemakers, artificial breast implants, and microencapsulated islet cells used in type 1 diabetes treatment. The foreign body response (FBR) is responsible for the development of a fibrous capsule, which is often detrimental to the function of the implanted device and therefore affected patients. One event leading to fibrous capsule formation is contraction of collagen by myofibroblasts. The objective of this project was to significantly reduce the thickness of the fibrous capsule by limiting fibroblast to myofibroblast differentiation. It was hypothesized that using lysine-based biomaterials with amidine-like functional group modifications would inhibit matrix metalloproteinase (MMP) activity, a precursor to myofibroblast formation. MMP Inhibition would impede cleavage of latent transforming growth factor beta (L-TGF-β) to transforming growth factor beta (TGF-β), a cytokine that stimulates fibroblast to myofibroblast differentiation. Cell staining was performed on NIH 3T3 fibroblasts cultured on each biomaterial and stimulated by L-TGF-β and TGF-β to evaluate material performance. Fibroblast viability was found to be \u3e70% on each material. These biomaterials have potential for use as a coating of microencapsulated islet cells for diabetes therapy. This study is also important for furthering understanding of the biology involved in fibrous capsule formation

Using Biomaterials to Reduce Fibrous Encapsulation of Biomedical Implants

Fibrous encapsulation, commonly referred to as scar formation, can cause failure in many biomedical implants, such as in the artificial pancreas for type I diabetes treatment. Scar tissue prevents wastes and nutrients from being able to be exchanged in the implant, ultimately rendering the treatment painful or ineffective. For example, one potential therapeutic for type I diabetes involves using a polymer to protect insulin-producing cells. This artificial pancreas provides diabetics with their much needed insulin on-demand. If scar tissue forms around this artificial pancreas, the device loses the ability to deliver insulin and becomes useless. Our goal is to reduce the fibrous encapsulation of implants using biomaterials and improve the understanding of how cells involved in scar formation respond to biomaterials. We show that our materials can reduce fibrous capsule formation by inhibiting certain physiological pathways. This research will not only improve the success of the artificial pancreas, but other biomaterials

Telemedicine of family-based treatment for adolescent anorexia nervosa: A protocol of a treatment development study.

BackgroundFamily-based treatment is an efficacious treatment available for adolescents with anorexia nervosa. Yet the implementation of this treatment, at least in the United States, is challenging due to a limited number of trained family-based treatment therapists and the concentration of these therapists in a limited number of urban centers. The use of telemedicine in the delivery of family-based treatment can increase access to this therapy for this patient population.Methods/designThis two-year treatment development study (December 2013-November 2015) follows a two-wave iterative case series design. The study is ongoing and addresses the treatment needs of families in remote, rural, or underrepresented parts of the United States by delivering family-based treatment via telemedicine (video chat). The first six months of the study was dedicated to selecting a cloud-based secure telemedicine portal for use with participants. Recruitment for the first of two consecutive case series (N = 5) began during month seven. After these five patients completed treatment, a systematic review of treatment via feedback from participants and therapists related to the delivery of this model and use of technology was completed. A second wave of recruitment is underway (N = 5). At the end of both waves (N = 10), and after a second review of treatment, we should be able to establish the feasibility and acceptability of family-based treatment delivered via telemedicine for this patient population.DiscussionThis study is the first attempt to deliver family-based treatment for adolescents with anorexia nervosa via telemedicine. If delivering family-based treatment in this format is feasible, it will provide access to an evidence-based treatment for families heretofore unable to participate in specialist treatment for their child's eating disorder