Cytokine mRNA profile of Epstein-Barr virus-stimulated highly differentiated T cells in multiple sclerosis: a pilot study.

The reason why EBV-specific cellular immune responses are abnormal in multiple sclerosis (MS) patients is still missing. In this exploratory pilot study, we assessed IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-17, IFN-gamma, TGF-beta1 and FOXP3 mRNA expression in EBV-stimulated highly differentiated T cells (T(HD)) of MS patients and healthy controls (HC). We found increased levels of IFN-gamma and IL-4 mRNA in CD8+ T(HD) cells of MS patients. All the other tested molecules were expressed similarly in MS patients and HC. Interestingly, increased IFN-gamma and IL-4 suggest that the control of EBV replication may be insufficient in MS patients.

Proteostasis of aging and stem cells

Estudi realitzat a partir d’una estada a la the Salk Institute, Estats Units, entre 2010 i 2012. L'estabilitat del genoma és essencial per a la supervivència de les cèl • lules mare, però, l'estabilitat del proteoma pot tenir un paper igualment important en la identitat de cèl • lules mare i la seva funció. La nostra hipòtesi és que les cèl • lules mare tenen la capacitat de proteostasis augmentada en comparació amb els seus homòlegs diferenciats i ens varem preguntar si l'activitat del proteasoma és diferent a les cèl • lules mare embrionàries humanes (hESCs). En particular, els nostres resultats mostren que les poblacions de cèl• lules mare presenten una activitat del proteasoma que es correlaciona amb majors nivells de la subunitat 19S del proteasoma PSMD11/RPN-6 i un corresponent augment del ensamblatge del 26S/30S proteasoma. L'expressió ectòpica de PSMD11 és suficient per augmentar l'activitat del proteasoma. Sorprenentment, varem trobar que la llarga vida del GLP-1 C. elegans mutant té també un augment dramàtic en l'activitat del proteasoma associat a nivells augmentats en l'expressió de RPN-6. El factor de transcripció DAF-16 és essencial per l'augment de la longevitat de GLP-1 i els cucs mutants que trobem DAF-16 necessari per a l'augment d'expressió de RPN-6 i, per tant, per l'activació de l'activitat del proteasoma en GLP-1 mutant animals. Una possibilitat interessant és que els gens que regulen la vida i la resistència a l'estrès en C. elegans poden també regular la funció hESCs de mamífer, cèl • lules que son considerades immortals. Aquests resultats ens van portar a la conclusió de que FOXO4, un factor de transcripció sensible a la insulina/IGF-1, regula l'activitat del proteasoma en hESCs, el que suggereix un paper per FOXO4 en la funció d’aquestes cèl • lules. En efecte, FOXO4 es necessari per a la diferenciació en llinatges neuronals de les hESCs. Els nostres resultats estableixen una nova regulació de laproteostasis en hESCs que uneix la longevitat i la resistència a l'estrès en invertebrats amb la funció i identitat de les hESCs.

Comparison of the metabolic and endocrine effects of 3,5,3'-triiodothyroacetic acid and thyroxine.

To test the hypothesis that 3,5,3'-triiodothyroacetic acid (Triac) is more active as a TSH suppressor than on peripheral parameters of thyroid hormone action, the following parameters were studied: basal metabolic rate, sleeping energy expenditure (SEE), sex hormone-binding globulin, and cholesterol. In a double blind trial, 14 subjects received during 3 weeks (phase 1) 180 micrograms T4 or 1700 micrograms Triac daily, divided into 3 doses, to suppress thyroidal secretion. The dosage was doubled for the next 3 weeks (phase 2). Under T4 treatment, TSH reached 0.11 mU/L during phase 1 and less than 0.03 mU/L during phase 2. With Triac, a marked TSH inhibition occurred after 1 week (0.17 mU/L), followed by an escape during the following 2 weeks (0.63 mU/L). During phase 2, an almost complete TSH suppression was obtained (0.03 mU/L). Both Triac doses suppressed endogenous thyroid hormone secretion, as evidenced by T4 and rT3 levels. Both substances induced a 2-fold stimulation of sex hormone-binding globulin during phase 2. Serum cholesterol decreased similarly, without affecting the high/low density lipoprotein ratio. T4 increased SEE by 4.1% and 8.5% during phases 1 and 2. Triac failed to induce the expected peripheral metabolic responses of the thyroid hormones, as demonstrated by an unchanged SEE and basal metabolic rate. These results clearly show a preferential action of Triac on TSH suppression.

Selective neurodegeneration induced in rotation-mediated aggregate cell cultures by a transient switch to stationary culture conditions: a potential model to study ischemia-related pathogenic mechanisms.

Aggregating brain cell cultures at an advanced maturational stage (20-21 days in vitro) were subjected for 1-3 h to anaerobic (hypoxic) and/or stationary (ischemic) conditions. After restoration of the normal culture conditions, cell loss was estimated by measuring the release of lactate dehydrogenase as well as the irreversible decrease of cell type-specific enzyme activities, total protein and DNA content. Ischemia for 2 h induced significant neuronal cell death. Hypoxia combined with ischemia affected both neuronal and glial cells to different degrees (GABAergic neurons>cholinergic neurons>astrocytes). Hypoxic and ischemic conditions greatly stimulated the uptake of 2-deoxy-D-glucose, indicating increased glucose consumption. Furthermore, glucose restriction (5.5 mM instead of 25 mM) dramatically increased the susceptibility of neuronal and glial cells to hypoxic and ischemic conditions. Glucose media concentrations below 2 mM caused selective neuronal cell death in otherwise normal culture conditions. GABAergic neurons showed a particularly high sensitivity to glucose restriction, hypoxia, and ischemia. The pattern of ischemia-induced changes in vitro showed many similarities to in vivo findings, suggesting that aggregating brain cell cultures provide a useful in vitro model to study pathogenic mechanisms related to brain ischemia.

Effect of the Scapulo-Humeral Rhythm on Anatomical and Reverse Shoulder Prostheses

Introduction: Several studies have reported significant alteration of the scapula-humeral rythm after total shoulder arthroplasty. However, the biomechanical and clinical effects, particularly on implants lifespan, are still unknown. The goal of this study was to evaluate the biomechanical consequences of an altered scapula-humeral rhythm. Methods: A numerical musculoskeletal model of the shoulder was used. The model included the scapula, the humerus and 6 scapulohumeral muscles: middle, anterior, and posterior deltoid, supraspinatus, subscapularis and infraspinatus combined with teres minor. Arm motion and joint stability were achieved by muscles. The reverse and anatomic Aequalis prostheses (Tornier Inc) were inserted. Two scapula-humeral rhythms were considered for each prosthesis: a normal 2:1 rhythm, and an altered 1:2 rhythm. For the 4 configurations, a movement of abduction in the scapular plane was simulated. The gleno-humeral force and contact pattern, but also the stress in the polyethylene and cement were evaluated. Results: With the anatomical prosthesis, the gleno-humeral force increased of 23% for the altered rhythm, with a more eccentric (posterior and superior) contact. The contact pressure, polyethylene stress, and cement stress increased respectively by 20%, 48% and 64%. With the reverse prosthesis, the gleno-humeral force increased of 11% for an altered rhythm. There was nearly no effect on the contact pattern on the polyethylene component surface. Conclusion: The present study showed that alteration oft the scapula-humeral rythm induced biomechanical consequences which could preclude the long term survival of the glenoid implant of anatomic prostheses. However,an altered scapula-humeral rhythm, even severe, should not be a contra indication for the use of a reverse prosthesis. 

Influence of the Premium Subsidy on Farmers’ Crop Insurance Coverage Decisions, April 2005

The Agricultural Risk Protection Act greatly increased the expected marginal net benefit of farmers buying high-coverage crop insurance policies by coupling premium subsidies to coverage level. This policy change, combined with cross-sectional variations in expected marginal net benefits of high-coverage policies, is used to estimate the role that premium subsidies play in farmers’ crop insurance decisions. We use county data for corn, soybeans, and wheat to estimate regression equations that are then used to obtain insight into two policy scenarios. We first estimate that eventual adoption of actuarially fair incremental premiums, combined with current coupled subsidies, would increase farmers’ purchase of high-coverage policies by almost 400 percent from 1998 levels across the three crops and two plans of insurance included in the analysis. We then estimate that a return to decoupled subsidies would decrease farmers’ high-coverage purchase decisions by an average of 36 percent.

Role of transcription factor PROX1 in colon cancer metastasis

Initiation and progression of most colorectal cancers (CRCs) are driven by hyper-activation of the canonical Wnt/ß-catenin/TCF signaling pathway. However, a basal level of activation of this pathway is necessary for intestinal cell homeostasis; thus only CRC-specific effectors of this pathway could be exploited as potential clinical targets. PROX1 is an evolutionary conserved transcription factor with multiple roles in several tissues in embryogenesis, and increasing relevance in cancer. PROX1 is a colon cancer-specific Wnt target in the intestine, thus it might represent a therapeutic target. The role of PROX1 in promoting the transition from early to highly-dysplastic adenoma was previously described [1], Importantly, tumor metastasis is a leading cause of cancer-related mortality. Frequently, micrometastases are already present in patients at the time of diagnosis, therefore better understanding of the mechanisms regulating growth of macrometastatic lesions is important for the development of novel treatment approaches. In this study we showed that PROX1 is expressed in colon cancer stem cell and promotes the outgrowth of metastatic lesions. Firstly, we analyzed the expression of PROX1 in advanced CRCs and their metastases. We found that PROX1 over-expression is a feature of microsatellite stable tumors (~85% of microsatellite stable (MSS) CRCs), which generally have worse prognosis in comparison to microsatellite unstable CRCs. Analysis of primary CRCs and corresponding metastatic lesions showed that PROX1 expression is conserved, or increased in metastases. Further bioinformatics analysis of tumor and metastases gene expression profiles showed that PROX1 is co- expressed with stem cell and progenitor markers. Moreover, in inducible ApcmLgr5-EGFP-lres-CreERT2 model, Prox1+ cells marked a sub-population of Lgr5+ stem cells and subsequent transient amplifying cell population. Orthotopic model of CRC and lung colonization assays in mice demonstrated that PROX1 promotes tumor cell outgrowth in metastatic lesions, while it has no effect on primary tumor growth, invasion, and survival in circulation or cell extravasation. In vitro, PROX1 expressing tumor cells demonstrated strongly increased capacity to form spheroids, and increased survival and proliferation under hypoxic or nutrient-deprivation conditions. By monitoring cellular respiration under these conditions, we found that PROX1 expressing cells exhibit a better metabolic adaptation to changes in fuel source. Autophagy inhibitors, prevented growth both in vitro and in vivo of PROX1 expressing cells. Importantly, conditional inactivation of PROX1 after the establishment of metastases prevented further growth of macroscopic lesions resulting in stable disease. In summary, we identified a novel mechanism underlying the ability of metastatic colon cancer stem and progenitor cells to survive and grow in target organs through metabolic adaptation. Our results establish PROX1 as a key factor of CRC metastatic disease where it promotes survival of metastatic colon cancer stem-like cells, through their metabolic adaptation in sub-optimal microenvironments - L'initiation et la progression de la plupart des cancers colorectaux (CRC) sont entraînées par une hyper-activation de la voie métabolique Wnt/ß- caténine/TCF. Toutefois, un niveau d'activation minimal de Wnt est nécessaire pour l'homéostasie des cellules intestinales ; ainsi seuls des effecteurs spécifiques du CRC- de cette voie pourraient être exploités comme des cibles cliniques potentielles. PROX1 est un facteur de transcription évolutif conservé avec de multiples rôles dans plusieurs tissus durant l'embryogenèse et une pertinence croissante dans le cancer. PROX1 est une cible Wnt spécifique dans le cancer de l'intestin, donc il pourrait représenter une cible thérapeutique. Le rôle de PROX1 durant l'évolution de la maladie d'un stade précoce jusqu'à l'adénome hautement dysplasique a été décrit précédemment. Surtout, la métastase des tumeurs est une cause majeure de mortalité liée au cancer. Souvent, les micro-métastases sont déjà présentes chez les patients au moment du diagnostic, c'est pourquoi une meilleure compréhension des mécanismes régulant la croissance des lésions macrométastatiques est importante pour le développement de nouvelles approches thérapeutiques. Dans cette étude, nous avons prouvé que PROX1 est exprimé dans les cellules souches du cancer du côlon et favorise l'apparition de lésions métastatiques. Nous avons d'abord analysé l'expression de PROX1 dans des CRC avancés ainsi que dans leurs métastases. Nous avons constaté que la surexpression de PROX1 est une caractéristique des tumeurs stables microsatellites (~85% du MSS CRC), qui ont généralement un pronostic défavorable par rapport aux microsatellites CRC instables. L'analyse des CRC primaires et de leurs métastases liées a montré que l'expression de PROX1 est conservée, voire augmentée dans les métastases. A l'aide d'une base de données de tumeurs et métastases, nous avons observé une co- régulation de PROX1 entre cellules souches et marqueurs de progéniteurs mais pas avec des cellules différenciées. De plus, en utilisant un modèle Apcm Lgr5-EGFP-IRES-CreERT2 inductible, les cellules Prox1+ ont marqué une sous-population de cellules LGR& capable de produire une lignée. Un modèle orthotopique de cancer colorectal et des essais de colonisation du poumon chez la souris ont démontré que PROX1 favorise l'excroissance des cellules tumorales dans les lésions métastatiques, alors qu'il n'a aucun effet sur la croissance tumorale primaire, l'invasion ou une extravasation des cellules. In vitro, les cellules tumorales exprimant PROX1 ont démontré une forte augmentation de leur capacité à former des sphéroïdes, ainsi qu'une augmentation de la survie et de la prolifération dans des conditions hypoxiques ou lors de privation de nutriments. En contrôlant la respiration cellulaire dans ces conditions, nous avons constaté que les cellules exprimant PROX1 présentent une meilleure adaptation métabolique à l'évolution des sources de carburant. Des inhibiteurs de l'autophagie, suggérant une approche thérapeutique potentielle, ont tué à la fois in vitro et in vivo les cellules exprimant PROX1. Surtout, l'inactivation conditionnelle de PROX1 après l'apparition de métastases a empêché la croissance des lésions macroscopiques résultant en une maladie stable. En résumé, nous avons identifié un nouveau mécanisme mettant en évidence la capacité des cellules souches du cancer du côlon métastatique à survivre et à se développer dans les organes cibles grâce à l'adaptation métabolique. Nos résultats définissent PROX1 comme un facteur clé du cancer colorectal métastatique en favorisant la survie des cellules souches métastatiques apparentées au cancer du colon grâce à leur adaptation métabolique aux microenvironnements défavorables.

CB1 cannabinoid receptor modulates MDMA acute responses and reinforcement

Background: 3, 4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug widely abused by young people. The endocannabinoid system is involved in the addictive processes induced by different drugs of abuse. However, the role of this system in the pharmacological effects of MDMA has not been yet clarified.Methods: Locomotion, body temperature and anxiogenic-like responses were evaluated after acute MDMA administration in CB1 knockout mice. Additionally, MDMA rewarding properties were investigated in the place conditioning and the intravenous self-administration paradigms. Extracellular levels of DA in the nucleus accumbens were also analyzed after a single administration of MDMA by in vivo microdialysis. Results: Acute MDMA administration increased locomotor activity, body temperature and anxiogenic-like responses in wild type mice, but these responses were lower or abolished in knockout animals. MDMA produced similar conditioned place preference and increased dopamine extracellular levels in the nucleus accumbens in both genotypes. Nevertheless, CB1 knockout mice failed to self-administer MDMA at any of the doses used. Conclusions: These results indicate that CB1 cannabinoid receptors play an important role in the acute prototypical effects of MDMA, and are essential in the acquisition of an operant behavior to self-administer this drug.

Vitamine D: actualité et recommandations [Vitamin D: update and recommendations].

The number of studies related to vitamin D has increased exponentially in recent years and it becomes difficult to integrate these data into daily practice. This article focuses on the practice by offering an overview on screening, needs, treatment and consequences of deficiency. While in some areas, a consensus seems to emerge, other issues still require a lot of research in order to have an impact on practice. Independently of the threshold values we use, there is an increased prevalence, which makes vitamin D deficiency the most common and also the most underdiagnosed deficiency. Vitamin D is like a marker of good health and a marker of the evolution of our society. How can be used this marker by the practitioner?

Long-Range Goals for Iowa's Criminal& Junvenile Justice Systems, 2005

The attached plan builds upon work done over the last decade. The first plan developed after the creation of the Division of Criminal and Juvenile Justice Planning in 1986 was issued in 1990 and annually updated through 1994. Since 1992, the CJJPAC has been required to coordinate their planning activities with those of the Iowa Juvenile Justice Advisory Council (JJAC). In 1995, these two councils developed a new plan consisting of a set of long-range justice system goals to assist policy makers and justice system practitioners as they plan and operate the justice system through the next twenty years. The statutory mandate for such long-range planning required the identification of goals specific enough to provide guidance, but broad enough to be of relevance over a long period of time. The long-range goals adopted by these councils in 1995 covered a wide variety of topics and offered a framework within which current practices could be defined and assessed. Collectively, these long-range goals were meant to provide a single source of direction to the complex assortment of practitioners and policymakers whose individual concerns and decisions collectively define the nature and effectiveness of Iowa’s justice system. The twenty-year goals established in 1995 were reviewed by the councils in 2000 to assess their current relevance. It was determined that, with a few revisions, the goals established in 1995 should be restated in 2000 with a renewed emphasis on their long-range status. This plan builds upon those issued in 1995 and 2000, continuing much of the emphasis of plans, with some new directions charted as appropriate.

Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.

PURPOSE: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents. MATERIALS AND METHODS: Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured. RESULTS: After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection. CONCLUSION: Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

Acute life-threatening presentation of vitamin d deficiency rickets.

Context: Clinical manifestations of vitamin D deficiency rickets are widely described; however cardiorespiratory arrest is an extremely rare presentation. Objective: The aim of this paper is to present the symptoms of severe vitamin D deficiency rickets and to highlight the importance of vitamin D prophylaxis in infants. Results: We report a case of a 16-month-old infant who presented to emergency room with a stridor that evolved into a full cardiorespiratory arrest secondary to hypocalcemia. Medical history revealed that the infant was exclusively breastfed without vitamin D supplementation until the age of 10 months. Due to cultural habits, his diet was also grossly deficient in dairy products. Physical exam revealed clinical signs of rickets. Laboratory test showed severe hypocalcemia, elevated alkaline phosphatase, normal serum phosphorous, decreased 25(OH) cholecalciferol, increased intact parathyroid hormone level, and normal urine calcium excretion. The radiography of the wrist showed evidence of cupping, fraying, metaphyseal widening, and demineralization of the distal radial and ulnar metaphyses. The bone mineral density of the lumbar spine measured by dual x-ray absorptiometry showed a Z-score below -2 SD. His cardiorespiratory arrest secondary to hypocalcemia was therefore attributed to severe nutritional rickets. Conclusion: Vitamin D deficiency rickets can be life threatening. Vitamin D supplementation is therefore crucial, especially in breastfed infants and some ethnic minorities (dark-skinned people, poor sun exposure), more at risk for developing severe rickets if not supplemented.

SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis.

The calcium-binding protein calretinin has emerged as a useful marker for the identification of mesotheliomas of the epithelioid and mixed types, but its putative role in tumor development has not been addressed previously. Although exposure to asbestos fibers is considered the main cause of mesothelioma, undoubtedly, not all mesothelioma patients have a history of asbestos exposure. The question as to whether the SV40 virus is involved as a possible co-factor is still highly debated. Here we show that increased expression of SV40 early gene products in the mesothelial cell line MeT-5A induces the expression of calretinin and that elevated calretinin levels strongly correlate with increased resistance to asbestos cytotoxicity. Calretinin alone mediates a significant part of this protective effect because cells stably transfected with calretinin cDNA were clearly more resistant to the toxic effects of crocidolite than mock-transfected control cells. Down-regulation of calretinin by antisense methods restored the sensitivity to asbestos toxicity to a large degree. The protective effect observed in clones with higher calretinin expression levels could be eliminated by phosphatidylinositol 3-kinase (PI3K) inhibitors, implying an important role for the PI3K/AKT signaling (survival) pathway in mediating the protective effect. Up-regulation of calretinin, resulting from either asbestos exposure or SV40 oncoproteins, may be a common denominator that leads to increased resistance to asbestos cytotoxicity and thereby contributes to mesothelioma carcinogenesis.

Hakunilan Kultsa/Urban II hanke : pohdintaa yhteisöteatterin merkityksestä alueelle

This thesis analyses what local community theatre activity means to an area and its residents, and whether this kind of activity is meaningful. The objective was to explore whether and how community art can help urban areas to move in the direction of sustainable development: whether art can be part of regional policy development work. Hakunilan Kultsa was founded in 2003. It is an Urban II, European Union project and part of the Community Iniative Programme 2001-2006, financed by the EU. Hakunilan Kultsa is also a co-operation between Vantaa city council's culture and youth services. The project encourages Hakunila residents of different ages to take part in versatile art and cultural intrests in the Hakunila youth centre. People have the opportunity to participate in theatre, expression, arts, dance, performing arts and writing groups. One of the main aims is to found a sustainable community theatre in the area. The thesis examines what effects Hakunilan Kultsa has had so far. Inquiry form and thematical interviews have been used as research methods. Interviews and questionnaires were gathered between Autumn 2004 and Spring 2005. The whole process lasted from Spring 2004 until Spring 2006. The author also made participatory observations during the research process which in turn affected the conclusions. The thesis also deals with associated topics such as urban programmes, sustainable development, Hakunila as a suburban area, resident stimulation, and community thetare work. Hakunilan Kultsa has proved its importance. Based on the enquiries and interviews, the project has effectively presented the possibility for art forms to become hobbies. There is no cultural, age or economical discrimination. The easily accessible site and the low threshold principle make it easy for people to participate. The community theatre has improved the area's public image, increased participation and initiative, and given a voice to the community.

Social Security in Theory and Practice (II): Efficiency Theories, Narrative Theories, and Implications for Reform

166 countries have some kind of public old age pension. What economic forces create and sustain old age Social Security as a public program? Mulligan and Sala-i-Martin (1999b) document several of the internationally and historically common features of social security programs, and explore "political" theories of Social Security. This paper discusses the "efficiency theories", which view creation of the SS program as a full of partial solution to some market failure. Efficiency explanations of social security include the "SS as welfare for the elderly" the "retirement increases productivity to optimally manage human capital externalities", "optimal retirement insurance", the "prodigal father problem", the "misguided Keynesian", the "optimal longevity insurance", the "government economizing transaction costs", and the "return on human capital investment". We also analyze four "narrative" theories of social security: the "chain letter theory", the "lump of labor theory", the "monopoly capitalism theory", and the "Sub-but-Nearly-Optimal policy response to private pensions theory". The political and efficiency explanations are compared with the international and historical facts and used to derive implications for replacing the typical pay-as-you-go system with a forced savings plan. Most of the explanations suggest that forced savings does not increase welfare, and may decrease it.