Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Genetic and phenotypic population divergence on a microgeographic scale in brown trout.

Salmonid populations of many rivers are rapidly declining. One possible explanation is that habitat fragmentation increases genetic drift and reduces the populations' potential to adapt to changing environmental conditions. We measured the genetic and eco-morphological diversity of brown trout (Salmo trutta) in a Swiss stream system, using multivariate statistics and Bayesian clustering. We found large genetic and phenotypic variation within only 40 km of stream length. Eighty-eight percent of all pairwise F(ST) comparisons and 50% of the population comparisons in body shape were significant. High success rates of population assignment tests confirmed the distinctiveness of populations in both genotype and phenotype. Spatial analysis revealed that divergence increased with waterway distance, the number of weirs, and stretches of poor habitat between sampling locations, but effects of isolation-by-distance and habitat fragmentation could not be fully disentangled. Stocking intensity varied between streams but did not appear to erode genetic diversity within populations. A lack of association between phenotypic and genetic divergence points to a role of local adaptation or phenotypically plastic responses to habitat heterogeneity. Indeed, body shape could be largely explained by topographic stream slope, and variation in overall phenotype matched the flow regimes of the respective habitats.

Dépistage et prévention chez les aînés: quelles interventions proposer, à qui, et jusqu'à quel âge [Screening and prevention in the elderly: which interventions should be proposed, to whom, and up to what age?].

Recommendations on preventive services rarely mention how to apply them to older people. Even though general criteria (prevalence of disease, quality of screening tests) that influence screening's efficacy remain important, appropriateness of screening in older persons depends much more on individual criteria, such as comorbidity, functional status, and life expectancy. More than with any other age group, patients preferences regarding future investigation and treatment guide the clinical decision. This article focuses on primary and secondary prevention, and discusses specific criteria to consider in each patient. A table summarizes the appropriate recommendations.

Multifocalité du carcinome épidermoïde sur les voies digestive supérieure et respiratoire distale : technicité du diagnostic endoscopique [Multiple squamous cell carcinoma of the upper digestive and lower respiratory tracts : methodology of endoscopic screening]

L'étude porte sur 951 porteurs d'un cancer primaire bucco-pharyngo-laryngé, et révèle un taux de multifocalité du carcinome épidermoïde sur les voies digestive supérieure (bouche-pharynx-oesophage) et aérienne distale (larynx-trachée-bronches) s'élevant à 14,5 %. Les secondes localisations peuvent être simultanées (6,4 %) ou successives (8,1 %) à la découverte du premier cancer: dès la deuxième année du follow-up leur incidence dépasse celle des récidives. Elles se localisent tant au niveau ORL (8,5 %) qu'oesophagien (3 %) ou bronchique (3 %). Le cancer du voile présente un taux de multifocalité particulièrement élevé (51 %). Les auteurs décrivent un type d'endoscopie de dépistage (bucco-pharyngo-oesophago-laryngo-trachéobronchoscopie) dont la fiabilité repose sur une technicité spécifique d'une part, et sur la connaissance des caractéristiques propres aux secondes localisations d'autre part. Ce dépistage systématique permet de détecter les tumeurs secondaires à un stade le plus souvent précoce et encore asymptomatique.

Dépistage du syndrome des apnées du sommeil [Screening for sleep apnea syndrome]

Sleep apnea syndrome (SAS) consists of nocturnal snoring interrupted by obstructive apnea and of diurnal symptoms like hypersomnolence as a consequence of sleep fragmentation. Cardiovascular morbidity and mortality associated with this syndrome justify early detection and appropriate treatment. Polysomnography is still a frequently used method for early detection; however, several disadvantages like duration, discomfort and expense led to a search for alternatives. Since the beginning of the eighties, oximetry allows recording of nocturnal oxygen saturation of hemoglobin even at home. Nocturnal oximetry reveals O2-desaturation associated with apnea and thus permits often to diagnose or exclude SAS. Diagnosis of SAS is made when at least 20 desaturations per hour with an amplitude of at least 4% are recorded. On the other hand, normal nocturnal oximetry nearly excludes SAS. In those cases where nocturnal oximetry is not diagnostic, polysomnography remains the method of choice. Departing from published work, a model for SAS detection, based mainly on nocturnal oximetry, is proposed.

Performance of blood pressure-to-height ratio at a single screening visit for the identification of hypertension in children.

BACKGROUND: The diagnosis of hypertension in children is difficult because of the multiple sex-, age-, and height-specific thresholds to define elevated blood pressure (BP). Blood pressure-to-height ratio (BPHR) has been proposed to facilitate the identification of elevated BP in children. OBJECTIVE: We assessed the performance of BPHR at a single screening visit to identify children with hypertension that is sustained elevated BP. METHOD: In a school-based study conducted in Switzerland, BP was measured at up to three visits in 5207 children. Children had hypertension if BP was elevated at the three visits. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for the identification of hypertension were assessed for different thresholds of BPHR. The ability of BPHR at a single screening visit to discriminate children with and without hypertension was evaluated with receiver operating characteristic (ROC) curve analyses. RESULTS: The prevalence of systolic/diastolic hypertension was 2.2%. Systolic BPHR had a better performance to identify hypertension compared with diastolic BPHR (area under the ROC curve: 0.95 vs. 0.84). The highest performance was obtained with a systolic BPHR threshold set at 0.80 mmHg/cm (sensitivity: 98%; specificity: 85%; PPV: 12%; and NPV: 100%) and a diastolic BPHR threshold set at 0.45 mmHg/cm (sensitivity: 79%; specificity: 70%; PPV: 5%; and NPV: 99%). The PPV was higher among tall or overweight children. CONCLUSION: BPHR at a single screening visit had a high performance to identify hypertension in children, although the low prevalence of hypertension led to a low PPV.

Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability.

The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.

Pathogen-induced hatching and population-specific life-history response to water-borne cues in brown trout (Salmo trutta)

Hatching is an important niche shift, and embryos in a wide range of taxa can either accelerate or delay this life-history switch in order to avoid stage-specific risks. Such behavior can occur in response to stress itself and to chemical cues that allow anticipation of stress. We studied the genetic organization of this phenotypic plasticity and tested whether there are differences among populations and across environments in order to learn more about the evolutionary potential of stress-induced hatching. As a study species, we chose the brown trout (Salmo trutta; Salmonidae). Gametes were collected from five natural populations (within one river network) and used for full-factorial in vitro fertilizations. The resulting embryos were either directly infected with Pseudomonas fluorescens or were exposed to waterborne cues from P. fluorescens-infected conspecifics. We found that direct inoculation with P. fluorescens increased embryonic mortality and induced hatching in all host populations. Exposure to waterborne cues revealed population-specific responses. We found significant additive genetic variation for hatching time, and genetic variation in trait plasticity. In conclusion, hatching is induced in response to infection and can be affected by waterborne cues of infection, but populations and families differ in their reaction to the latter.

Testing for local adaptation in brown trout using reciprocal transplants.

ABSTRACT: BACKGROUND: Local adaptation can drive the divergence of populations but identification of the traits under selection remains a major challenge in evolutionary biology. Reciprocal transplant experiments are ideal tests of local adaptation, yet rarely used for higher vertebrates because of the mobility and potential invasiveness of non-native organisms. Here, we reciprocally transplanted 2500 brown trout (Salmo trutta) embryos from five populations to investigate local adaptation in early life history traits. Embryos were bred in a full-factorial design and raised in natural riverbeds until emergence. Customized egg capsules were used to simulate the natural redd environment and allowed tracking the fate of every individual until retrieval. We predicted that 1) within sites, native populations would outperform non-natives, and 2) across sites, populations would show higher performance at 'home' compared to 'away' sites. RESULTS: There was no evidence for local adaptation but we found large differences in survival and hatching rates between sites, indicative of considerable variation in habitat quality. Survival was generally high across all populations (55% +/- 3%), but ranged from 4% to 89% between sites. Average hatching rate was 25% +/- 3% across populations ranging from 0% to 62% between sites. CONCLUSION: This study provides rare empirical data on variation in early life history traits in a population network of a salmonid, and large-scale breeding and transplantation experiments like ours provide powerful tests for local adaptation. Despite the recently reported genetic and morphological differences between the populations in our study area, local adaptation at the embryo level is small, non-existent, or confined to ecological conditions that our experiment could not capture.

Five-Year Denosumab Treatment of Postmenopausal Women with Osteoporosis: Results from the first two Years of the Freedom Trial Extension

Objectives : The FREEDOM trial1 open-label extension is designed to evaluate the long-term efficacy and safety of denosumab for up to 10 years. We report the results from the first 2 years of the extension, representing up to 5 years of denosumab exposure.Materials/Methods : Postmenopausal women enrolled in the extension previously completed FREEDOM. During the extension, all women receive denosumab (60 mg) every 6 months and calcium and vitamin D daily. For the FREEDOM denosumab group, the data reflect 5 years of denosumab treatment (long-term group). For the FREEDOM placebo group, the data reflect 2 years of denosumab treatment (de novo group). P-values are descriptive.Results : There were 4550 (70.2%) FREEDOM women enrolled in the extension (2343 long-term; 2207 de novo). During the 4th and 5th years of denosumab treatment, the long-term group had further 1.9% and 1.7% increases in lumbar spine BMD and further 0.7% and 0.6% increases in total hip BMD (all P<0.0001 compared with extension baseline). Total BMD increases with 5-year denosumab treatment were 13.7% (lumbar spine) and 7.0% (total hip). In the de novo group, BMD increased during the first 2 years of denosumab treatment by 7.9% (lumbar spine) and 4.1% (total hip) (all P<0.0001 compared with extension baseline). After denosumab administration, serum CTX was rapidly and maximally reduced in both groups with the characteristic attenuation observed at the end of the dosing interval, as previously reported.2 Incidences of new vertebral and nonvertebral fractures were low and below rates observed in the FREEDOM placebo group. Adverse event reports were similar for both groups: in the long-term group, 83.4% reported AEs and 18.9% were serious. In the de novo group, the percentages were 82.8% and 19.4%, respectively. In FREEDOM, the respective percentages were 92.8% and 25.8% in the denosumab group and 93.1% and 25.1% in the placebo group. Two subjects in the de novo group had AEs adjudicated to ONJ which healed without further complications ; one resolved within the 6-month dosing interval and denosumab was continued. There were no atypical femoral fractures.Conclusions : Denosumab treatment for 5 years was well-tolerated and continued to significantly reduce CTX and significantly increase BMD. Reference: 1)Cummings;NEJM;2009;361:756, 2)Eastell;JBMR;2010; doi-10.1002/jbmr.251 Disclosure of Interest: This study was funded by Amgen; S Papapoulos: Consulting fees from Amgen, Merck, Novartis, Procter & Gamble, GSK, and Wyeth; R Chapurlat: Research grants and/or consulting fees from Amgen, Merck, Novartis, sanofi-aventis, Roche, Servier, and Warner Chilcott;ML Brandi: Research grants and/or consulting fees from Amgen, Eli Lily, GSK, MSD, NPS, Nycomed, Roche, Servier, and Stroder; JP Brown: Research grants and/or consulting or speaking fees from Abott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Novartis, Merck, and Warner Chilcott; E Czerwinski: Research grants from Amgen, Astrazeneca, Danone Research, Eli Lilly, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SantoSolve AS, and Servier; N Daizadeh, A Grauer, C Libanati: Employed by Amgen and own Amgen stocks or stock options; M-A Krieg, D Mellstrom, H Resch: None; S Radominski: Research grants from Amgen, Pfizer, Novartis, Bristol-Myers Squibb, Roche, and Aventis; Z Man: Lecture fees and/or consulting fees from Merck, Novartis, Roche, and sanofi-aventis. Novartis steering committee member; JA Roman: Research grants from Roche; J-Y Reginster: Research grants, consulting fees, and/or lecture fees from Amgen, Analis, Bristol Myers Squibb, Ebewee Pharma, Genevrier, GSK, IBSA, Lilly, Merck Sharp & Dhome, Negma, Novartis, Novo-Nordisk, Nycomed, NPS, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, UCB, Wyeth, and Zodiac; C Roux: Research grants and/or consulting fees from Amgen, MSD, Novartis, Servier, and Roche; SR Cummings: Research grants and/or consulting fees from Amgen, Eli Lilly, Novartis, and Merck; HG Bone: Research grants and/or consulting or speaking fees from Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda, and Zelos

Cost-effectiveness of opportunistic versus organised mammography screening in Switzerland

BACKGROUND: Various centralised mammography screening programmes have shown to reduce breast cancer mortality at reasonable costs. However, mammography screening is not necessarily cost-effective in every situation. Opportunistic screening, the predominant screening modality in several European countries, may under certain circumstances be a cost-effective alternative. In this study, we compared the cost-effectiveness of both screening modalities in Switzerland. METHODS: Using micro-simulation modelling, we predicted the effects and costs of biennial mammography screening for 50-69 years old women between 1999 and 2020, in the Swiss female population aged 30-70 in 1999. A sensitivity analysis on the test sensitivity of opportunistic screening was performed. RESULTS: Organised mammography screening with an 80% participation rate yielded a breast cancer mortality reduction of 13%. Twenty years after the start of screening, the predicted annual breast cancer mortality was 25% lower than in a situation without screening. The 3% discounted cost-effectiveness ratio of organised mammography screening was euro11,512 per life year gained. Opportunistic screening with a similar participation rate was comparably effective, but at twice the costs: euro22,671-24,707 per life year gained. This was mainly related to the high costs of opportunistic mammography and frequent use of imaging diagnostics in combination with an opportunistic mammogram. CONCLUSION: Although data on the performance of opportunistic screening are limited, both opportunistic and organised mammography screening seem effective in reducing breast cancer mortality in Switzerland. However, for opportunistic screening to become equally cost-effective as organised screening, costs and use of additional diagnostics should be reduced.

MRSA screening by the Xpert MRSA PCR assay: pooling samples of the nose, throat, and groin increases the sensitivity of detection without increasing the laboratory costs.

The performance of the Xpert MRSA polymerase chain reaction (PCR) assay on pooled nose, groin, and throat swabs (three nylon flocked eSwabs into one tube) was compared to culture by analyzing 5,546 samples. The sensitivity [0.78, 95 % confidence interval (CI) 0.73-0.82] and specificity (0.99, 95 % CI 0.98-0.99) were similar to the results from published studies on separated nose or other specimens. Thus, the performance of the Xpert MRSA assay was not affected by pooling the three specimens into one assay, allowing a higher detection rate without increasing laboratory costs, as compared to nose samples alone.

Obesity and overweight associated with lower rates of colorectal cancer screening in Switzerland.

Screening for colorectal cancer (CRC) is associated with reduced CRC mortality, but low screening rates have been reported in several settings. The aim of the study was to assess predictors of low CRC screening in Switzerland. A retrospective cohort of a random sample of 940 patients aged 50-80 years followed for 2 years from four Swiss University primary care settings was used. Patients with illegal residency status and a history of CRC or colorectal polyps were excluded. We abstracted sociodemographic data of patients and physicians, patient health status, and indicators derived from RAND's Quality Assessment Tools from medical charts. We defined CRC screening as colonoscopy in the last 10 years, flexible sigmoidoscopy in the last 5 years, or fecal occult blood testing in the last 2 years. We used bivariate and multivariate logistic regression analyses. Of 940 patients (mean age 63.9 years, 42.7% women), 316 (33.6%) had undergone CRC screening. In multivariate analysis, birthplace in a country outside of Western Europe and North America [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.45-0.97], male sex of the physician in charge (OR 0.67, 95% CI 0.50-0.91), BMI 25.0-29.9 kg/m (OR 0.66, CI 0.46-0.96) and at least 30.0 kg/m (OR 0.61, CI 0.40-0.90) were associated with lower CRC screening rates. Obesity, overweight, birthplace outside of Western Europe and North America, and male sex of the physician in charge were associated with lower CRC screening rates in Swiss University primary care settings. Physician perception of obesity and its impact on their recommendation for CRC screening might be a target for further research.

Financial Markets and Real Ecinomy: Four Essays in International Trade

Financial markets play an important role in an economy performing various functions like mobilizing and pooling savings, producing information about investment opportunities, screening and monitoring investments, implementation of corporate governance, diversification and management of risk. These functions influence saving rates, investment decisions, technological innovation and, therefore, have important implications for welfare. In my PhD dissertation I examine the interplay of financial and product markets by looking at different channels through which financial markets may influence an economy.My dissertation consists of four chapters. The first chapter is a co-authored work with Martin Strieborny, a PhD student from the University of Lausanne. The second chapter is a co-authored work with Melise Jaud, a PhD student from the Paris School of Economics. The third chapter is co-authored with both Melise Jaud and Martin Strieborny. The last chapter of my PhD dissertation is a single author paper.Chapter 1 of my PhD thesis analyzes the effect of financial development on growth of contract intensive industries. These industries intensively use intermediate inputs that neither can be sold on organized exchange, nor are reference-priced (Levchenko, 2007; Nunn, 2007). A typical example of a contract intensive industry would be an industry where an upstream supplier has to make investments in order to customize a product for needs of a downstream buyer. After the investment is made and the product is adjusted, the buyer may refuse to meet a commitment and trigger ex post renegotiation. Since the product is customized to the buyer's needs, the supplier cannot sell the product to a different buyer at the original price. This is referred in the literature as the holdup problem. As a consequence, the individually rational suppliers will underinvest into relationship-specific assets, hurting the downstream firms with negative consequences for aggregate growth. The standard way to mitigate the hold up problem is to write a binding contract and to rely on the legal enforcement by the state. However, even the most effective contract enforcement might fail to protect the supplier in tough times when the buyer lacks a reliable source of external financing. This suggests the potential role of financial intermediaries, banks in particular, in mitigating the incomplete contract problem. First, financial products like letters of credit and letters of guarantee can substantially decrease a risk and transaction costs of parties. Second, a bank loan can serve as a signal about a buyer's true financial situation, an upstream firm will be more willing undertake relationship-specific investment knowing that the business partner is creditworthy and will abstain from myopic behavior (Fama, 1985; von Thadden, 1995). Therefore, a well-developed financial (especially banking) system should disproportionately benefit contract intensive industries.The empirical test confirms this hypothesis. Indeed, contract intensive industries seem to grow faster in countries with a well developed financial system. Furthermore, this effect comes from a more developed banking sector rather than from a deeper stock market. These results are reaffirmed examining the effect of US bank deregulation on the growth of contract intensive industries in different states. Beyond an overall pro-growth effect, the bank deregulation seems to disproportionately benefit the industries requiring relationship-specific investments from their suppliers.Chapter 2 of my PhD focuses on the role of the financial sector in promoting exports of developing countries. In particular, it investigates how credit constraints affect the ability of firms operating in agri-food sectors of developing countries to keep exporting to foreign markets.Trade in high-value agri-food products from developing countries has expanded enormously over the last two decades offering opportunities for development. However, trade in agri-food is governed by a growing array of standards. Sanitary and Phytosanitary standards (SPS) and technical regulations impose additional sunk, fixed and operating costs along the firms' export life. Such costs may be detrimental to firms' survival, "pricing out" producers that cannot comply. The existence of these costs suggests a potential role of credit constraints in shaping the duration of trade relationships on foreign markets. A well-developed financial system provides the funds to exporters necessary to adjust production processes in order to meet quality and quantity requirements in foreign markets and to maintain long-standing trade relationships. The products with higher needs for financing should benefit the most from a well functioning financial system. This differential effect calls for a difference-in-difference approach initially proposed by Rajan and Zingales (1998). As a proxy for demand for financing of agri-food products, the sanitary risk index developed by Jaud et al. (2009) is used. The empirical literature on standards and norms show high costs of compliance, both variable and fixed, for high-value food products (Garcia-Martinez and Poole, 2004; Maskus et al., 2005). The sanitary risk index reflects the propensity of products to fail health and safety controls on the European Union (EU) market. Given the high costs of compliance, the sanitary risk index captures the demand for external financing to comply with such regulations.The prediction is empirically tested examining the export survival of different agri-food products from firms operating in Ghana, Mali, Malawi, Senegal and Tanzania. The results suggest that agri-food products that require more financing to keep up with food safety regulation of the destination market, indeed sustain longer in foreign market, when they are exported from countries with better developed financial markets.Chapter 3 analyzes the link between financial markets and efficiency of resource allocation in an economy. Producing and exporting products inconsistent with a country's factor endowments constitutes a serious misallocation of funds, which undermines competitiveness of the economy and inhibits its long term growth. In this chapter, inefficient exporting patterns are analyzed through the lens of the agency theories from the corporate finance literature. Managers may pursue projects with negative net present values because their perquisites or even their job might depend on them. Exporting activities are particularly prone to this problem. Business related to foreign markets involves both high levels of additional spending and strong incentives for managers to overinvest. Rational managers might have incentives to push for exports that use country's scarce factors which is suboptimal from a social point of view. Export subsidies might further skew the incentives towards inefficient exporting. Management can divert the export subsidies into investments promoting inefficient exporting.Corporate finance literature stresses the disciplining role of outside debt in counteracting the internal pressures to divert such "free cash flow" into unprofitable investments. Managers can lose both their reputation and the control of "their" firm if the unpaid external debt triggers a bankruptcy procedure. The threat of possible failure to satisfy debt service payments pushes the managers toward an efficient use of available resources (Jensen, 1986; Stulz, 1990; Hart and Moore, 1995). The main sources of debt financing in the most countries are banks. The disciplining role of banks might be especially important in the countries suffering from insufficient judicial quality. Banks, in pursuing their rights, rely on comparatively simple legal interventions that can be implemented even by mediocre courts. In addition to their disciplining role, banks can promote efficient exporting patterns in a more direct way by relaxing credit constraints of producers, through screening, identifying and investing in the most profitable investment projects. Therefore, a well-developed domestic financial system, and particular banking system, would help to push a country's exports towards products congruent with its comparative advantage.This prediction is tested looking at the survival of different product categories exported to US market. Products are identified according to the Euclidian distance between their revealed factor intensity and the country's factor endowments. The results suggest that products suffering from a comparative disadvantage (labour-intensive products from capital-abundant countries) survive less on the competitive US market. This pattern is stronger if the exporting country has a well-developed banking system. Thus, a strong banking sector promotes exports consistent with a country comparative advantage.Chapter 4 of my PhD thesis further examines the role of financial markets in fostering efficient resource allocation in an economy. In particular, the allocative efficiency hypothesis is investigated in the context of equity market liberalization.Many empirical studies document a positive and significant effect of financial liberalization on growth (Levchenko et al. 2009; Quinn and Toyoda 2009; Bekaert et al., 2005). However, the decrease in the cost of capital and the associated growth in investment appears rather modest in comparison to the large GDP growth effect (Bekaert and Harvey, 2005; Henry, 2000, 2003). Therefore, financial liberalization may have a positive impact on growth through its effect on the allocation of funds across firms and sectors.Free access to international capital markets allows the largest and most profitable domestic firms to borrow funds in foreign markets (Rajan and Zingales, 2003). As domestic banks loose some of their best clients, they reoptimize their lending practices seeking new clients among small and younger industrial firms. These firms are likely to be more risky than large and established companies. Screening of customers becomes prevalent as the return to screening rises. Banks, ceteris paribus, tend to focus on firms operating in comparative-advantage sectors because they are better risks. Firms in comparative-disadvantage sectors finding it harder to finance their entry into or survival in export markets either exit or refrain from entering export markets. On aggregate, one should therefore expect to see less entry, more exit, and shorter survival on export markets in those sectors after financial liberalization.The paper investigates the effect of financial liberalization on a country's export pattern by comparing the dynamics of entry and exit of different products in a country export portfolio before and after financial liberalization.The results suggest that products that lie far from the country's comparative advantage set tend to disappear relatively faster from the country's export portfolio following the liberalization of financial markets. In other words, financial liberalization tends to rebalance the composition of a country's export portfolio towards the products that intensively use the economy's abundant factors.