NUDGE: IMPROVING DECISIONS ABOUT HEALTH, WEALTH, AND HAPPINESS by Richard H. Thaler and Cass R. Sunstein Penguin Books, 2009, 312 pp, ISBN 978-0-14-311526-7This book is best described formally as a general explanation of and advocacy for libertarian paternalism, a term coined by the authors in earlier publications. Informally, it is about how leaders, systems, organizations, and governments can nudge people to do the things the nudgers want and need done for the betterment of the nudgees, or of society. It is paternalism in the sense that "it is legitimate for choice architects to try to influence people's behavior in order to make their lives longer, healthier, and better", (p. 5) It is libertarian in that "people should be free to do what they like - and to opt out of undesirable arrangements if they want to do so", (p. 5) The built-in possibility of opting out or making a different choice preserves freedom of choice even though people's behavior has been influenced by the nature of the presentation of the information or by the structure of the decisionmaking system. I had never heard of libertarian paternalism before reading this book, and I now find it fascinating.Written for a general audience, this book contains mostly social and behavioral science theory and models, but there is considerable discussion of structure and process that has roots in mathematical and quantitative modeling. One of the main applications of this social system is economic choice in investing, selecting and purchasing products and services, systems of taxes, banking (mortgages, borrowing, savings), and retirement systems. Other quantitative social choice systems discussed include environmental effects, health care plans, gambling, and organ donations. Softer issues that are also subject to a nudge-based approach are marriage, education, eating, drinking, smoking, influence, spread of information, and politics. There is something in this book for everyone.The basis for this libertarian paternalism concept is in the social theory called "science of choice", the study of the design and implementation of influence systems on various kinds of people. The terms Econs and Humans, are used to refer to people with either considerable or little rational decision-making talent, respectively. The various libertarian paternalism concepts and systems presented are tested and compared in light of these two types of people. Two foundational issues that this book has in common with another book, Network of Echoes: Imitation, Innovation and Invisible Leaders, that was also reviewed for this issue of the Journal are that 1 ) there are two modes of thinking (or components of the brain) - an automatic (intuitive) process and a reflective (rational) process and 2) the need for conformity and the desire for imitation are powerful forces in human behavior. …

Nudge: Improving Decisions about Health, Wealth, and Happiness

Two-photon absorption has important advantages over conventional one-photon absorption, which has led to applications in microscopy, microfabrication, three-dimensional data storage, optical power limiting, up-converted lasing, photodynamic therapy, and for the localized release of bio-active species. These applications have generated a demand for new dyes with high two-photon absorption cross-sections. This Review introduces the theory of two-photon absorption, surveys the wide range of potential applications, and highlights emerging structure-property correlations that can serve as guidelines for the development of efficient two-photon dyes.

Two-photon absorption and the design of two-photon dyes.

In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in developing PDT agents, and (iv) the various synthetic strategies designed at the Roswell Park Cancer Institute, Buffalo, for developing highly effective long-wavelength PDT agents and their utility in constructing the conjugates with tumor-imaging and therapeutic potential (Theranostics). The clinical status of certain selected PDT agents is also summarized (205 references).

The role of porphyrin chemistry in tumor imaging and photodynamic therapy

2. Activatable Photosensitizer Design Considerations 2842 2.1. Activation Strategy 2842 2.2. Photosensitizer Selection 2844 2.3. Photosensitizer Conjugation 2845 3. Examples of Activatable Photosensitizers 2845 3.1. Environment-Activated Photosensitizers 2845 3.2. Enzyme-Activated Photosensitizers 2846 3.3. Nucleic Acid-Activated Photosensitizers 2852 3.4. Other Activation Mechanisms 2853 4. Conclusion and Outlook 2855 5. Abbreviations 2855 6. Acknowledgments 2855 7. References 2855

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Activatable photosensitizers for imaging and therapy

Evaluating the quality of medical care.

It is more than 25 years since photodynamic therapy (PDT) was proposed as a useful tool in oncology, but the approach is only now being used more widely in the clinic. The understanding of the biology of PDT has advanced, and efficient, convenient, and inexpensive systems of light delivery are now available. Results from well-controlled, randomised phase III trials are also becoming available, especially for treatment of non-melanoma skin cancer and Barrett's oesophagus, and improved photosensitising drugs are in development. PDT has several potential advantages over surgery and radiotherapy: it is comparatively non-invasive, it can be targeted accurately, repeated doses can be given without the total-dose limitations associated with radiotherapy, and the healing process results in little or no scarring. PDT can usually be done in an outpatient or day-case setting, is convenient for the patient, and has no side-effects. Two photosensitising drugs, porfirmer sodium and temoporfin, have now been approved for systemic administration, and aminolevulinic acid and methyl aminolevulinate have been approved for topical use. Here, we review current use of PDT in oncology and look at its future potential as more selective photosensitising drugs become available.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(04)01529-3.pdf

The present and future role of photodynamic therapy in cancer treatment.

Increasing treatment specificity is one of the major aims of cancer research. Photodynamic therapy is a clinically proven treatment for some cancers and certain other diseases. Photosensitisers generally have little intrinsic selectivity for tumours and any accumulation is dependent upon the type of tumour involved. Increasing tumour selective accumulation could improve the efficacy of PDT and reduce any risk of side effects caused by photosensitiser accumulation in non-target tissue. In order to target photosensitisers to tumours, a cyclic peptide, cRGDfK (arginine-glycine-aspartic acid-phenylalanine-lysine) has been synthesised using solid phase peptide chemistry and conjugated to the porphyrin photosensitiser, protoporphyrin IX. The arginine-glycine-aspartic acid (RGD) motif has been shown to specifically bind αvβ3 integrins, heterodimeric glycoproteins upregulated on the surface of proliferating endothelial cells such as those in tumour neovasculature. This study reports the synthesis, in vitro and in vivo characterisation of this novel compound and compares its properties to the free photosensitiser. The individual components in our system, protoporphyrin IX and cRGDfK retain their respective photodynamic and integrin binding activity following the coupling step and produce a conjugate of high purity. The PpIX:cRGDfK conjugate is shown to be a good photosensitiser in vitro in the integrin positive human SiHa cell line and in vivo in a mouse CaNT tumour model. Moreover, pharmacokinetic analysis of PpIX:cRGDfK treated mice shows significant retention and accumulation of photosensitiser in tumour tissue with higher tumour : normal tissue ratios than the free photosensitiser. However, although the conjugate shows this higher accumulation and improved tumour : non-target tissue ratios, the overall in vivo PDT effect, between dose-light intervals of 0 and 6 h, is not significantly better than for free protoporphyrin IX This is possibly due to differences in the target environment or in the subcellular localisation of the compounds.

https://link.springer.com/content/pdf/10.1039/b715141a.pdf

In vivo and in vitro characterisation of a protoporphyrin IX–cyclic RGD peptide conjugate for use in photodynamic therapy

A roadmap for the early detection and diagnosis of cancer.

Photodynamic therapy (PDT) is a treatment combining a photosensitiser, molecular oxygen and visible light of characteristic wavelength to produce cytotoxic reactive oxygen species (ROS). Within our centre, a series of phenothiazinium salts were synthesised and initial characterisation studies performed to determine any potential use for PDT. All photosensitisers within the series were shown to have useful spectral properties for PDT, with absorbance lambdamax above 667 nm. The Log P values of the compounds were shown to range from -0.9 to > +2.0. Furthermore, Log P values were shown to be important in determining the site of subcellular localisation and as such the site of photooxidative damage. Derivatives with a Log P value of greater than +1.0 were shown to initially localise to the lysosomes then relocalise throughout the cytoplasm following illumination, whereas compounds with intermediate Log P values (-0.7 to +1.0) all remained lysosomal. Only methylene blue (Log P-0.9) was shown to redistribute to the nucleus upon illumination. Following treatment of RIF-1 cells with each phenothiazinium salt for 1 h and subsequent exposure to 665 nm laser light at a fluence rate of 10 mW cm(-2)(18 J cm(-2)), it was determined that the most potent photosensitiser was 260-fold more potent than methylene blue. Furthermore, the PDT efficacy of the photosensitisers was shown to be related to the level of mitochondrial damage induced directly following illumination.

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A comparative analysis of phenothiazinium salts for the photosensitisation of murine fibrosarcoma (RIF-1) cells in vitro.

Background More than 80% of global deaths caused by cardiovascular disease (CVD) and diabetes mellitus (DM) occur in developing countries. The burden of noncommunicable disease in South Asia is increasing rapidly. Objectives To estimate the costs of CVD and the costs of DM to individuals and society in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. Methods We systematically searched six health and economic databases for studies identifying costs related to CVD or DM and their respective complications. Costs were extracted from included studies and converted to US $ for the price year 2015 to enable meaningful comparisons. Results Of the 71 articles suitable for full-text review, 29 studies met the inclusion criteria. Most were cost-of-illness studies (n = 27) and were from the patient perspective (n = 23). Most collected data since 2000 (n = 23) and included data from India (n = 24). No studies included longitudinal costs at the patient level. Medical costs for routine management of CVD and DM were broadly similar. These costs escalate significantly once complications occur, which require treatment, particularly for stroke, major coronary events, and amputations. Costs are mainly borne by the individual and family. Some included studies modeled rapidly rising future costs. Most studies included had methodological weaknesses. Conclusions Marked increases in costs have been identified when complications of these chronic diseases occur, underlining the importance of secondary prevention approaches in disease management in South Asia. Higher quality studies, especially those that include longitudinal costs, are required to establish more robust cost estimates.

Ian Walker

Papers

The present and future role of photodynamic therapy in cancer treatment.

In vivo and in vitro characterisation of a protoporphyrin IX–cyclic RGD peptide conjugate for use in photodynamic therapy

A roadmap for the early detection and diagnosis of cancer.

A comparative analysis of phenothiazinium salts for the photosensitisation of murine fibrosarcoma (RIF-1) cells in vitro.

The Economic Costs of Cardiovascular Disease, Diabetes Mellitus, and Associated Complications in South Asia: A Systematic Review