Search

Background: Accelerated muscle and adipose tissue loss are two of the main aspects of cancer cachexia. β2-agonists seem to be successful in the treatment of cachexia in experimental animals. The aim if the present investigation was to study the effects on body weight loss in tumor-bearing animals of a combination of formoterol and AR-42, an inhibitor of histone deacetylase (HDAC). Methods: Rats were divided into two groups, namely controls (C) and tumor-bearing (T). TB group was further divided into four subgroups: untreated (saline as a vehicle), treated with Formoterol (F) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with AR-42 (A) (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). and double-treated treated (TFA) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and AR-42 (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). 7 days after tumor transplantation, muscle weights, grip force and total physical activity were determined in all experimental groups. Results: The presence of the Yoshida AH-130 ascites hepatoma induced severe muscle wasting in rats. Treatment of the tumor-bearing animals with the beta2-agonist formoterol (0,3 mg/kg), resulted in a significant improvement in the cachectic state of the animals. Treatment of the tumor-bearing animals with AR42 did not result in any effects on muscle wasting in the cachectic rats. Furthermore, the combination of formoterol and AR42 showed no additional effects to those observed with just formoterol. Conclusion: The results presented question the previously described effects of AR42 on cancer cachexia, probably due to its effect on tumor growth.

This article performs empirical research and finds a negative relationship between accidents in the workplace and financial performance. The relationship is stronger and more persistent for performance 1 year ahead than for the current year. We find no significant evidence of curvilinear U-shaped or inverted U-shaped relationships. Results are strong across different industries and samples, variable definitions and model specifications. The study contributes to the scarce extant research with reliable data and samples of a wide span of industries. The study also contributes methodologically with refined analyses of the curvilinear relationship and providing robust widespread inference for a large number of industries.

After the approval of a code of ethics, the creation of a permanent board‐level ethics committee is the next step in the institutionalization of business ethics. This study explores how the board's structure and demographic characteristics explain the decision to form an ethics committee. The analysis is based on the constituents of the Standard and Poor's Europe 350 index. Consistent with our hypotheses, we find that ethics committees are more likely to be found in firms with a lower presence of executive directors and of directors holding MBA degrees. However, we also observe that boards chaired by executive directors seem to favor the creation of an ethics committee. Additionally, as we had anticipated, firms with stronger agency conflicts seem to be more willing to create committees. The analysis conducted with segmented samples reveals that the model has greater explanatory power when applied to firms from common‐law and French civil‐law countries than when applied to firms from the German–Scandinavian civil‐law area. Finally, our results indicate that a firm's country of origin is a more influential factor in explaining the decision to create an ethics committee than the industry to which it belongs or even the magnitude of its agency conflicts.

We conduct empirical research on the flexibility of operating costs of e-commerce firms. With an international sample of firms from different European countries, we find that e-commerce firms have a different cost structure than traditional retail firms, with a lower share of labor costs and cost of goods sold, but a higher share of other operating costs. While we find no significant different behavior in cost of goods sold and labor costs between the two types of firms, e-commerce firms are more flexible in adjusting other operating costs than traditional retail firms when activity decreases. Results are robust to different models, estimations methods and samples. The higher flexibility of e-commerce firms relies on other operating costs, but e-commerce creates qualified jobs with higher wages than traditional retail, with no additional exposure to labor uncertainty for employees.

We investigate the effects of an exogenous demand shock arising from the award of public service contracts by Italian public administrations in 2015 on a sample of 1782 winning small and medium firms that were not awarded any contract during the previous 3 years. Using a difference-in-differences model with continuous treatments estimated on a propensity score matched sample, our results reveal that higher awarded values enhance various performance dimensions of the winning firms as well as their average payroll per employee. Nonetheless, higher winning rebates moderate the positive effects of the award on payroll by inducing the winning firms to downward manage both salaries and social security contributions per employee to maintain their desired level of performance. The effects are mostly significant for smaller microenterprises. In addition, winning rebates negatively affect the performance of firms in the construction industry by leading these firms to downward manage the payroll of their employees more aggressively than firms in other industries. Our findings provide novel insights for the implementation of industrial policies aimed at achieving sustainable macroeconomic and social goals, within the business fabric, through the effective management of public service procurement.

Purpose: The CASC-IN score has been designed with two very clear objectives: first, as a means to quantitatively assess pre-cachexia in cancer patients, and second, as a tool to discriminate the patients where cachexia staging is relevant. From this point of view, the CASC-IN tool is tightly linked with the so-called CAchexia SCOre (CASCO) previously described1 and validated2 by our research team. The results presented here classify a population of cancer patients into non-cachectic, precachectic or cachectic. Patients and Methods: An observational prospective case-control study has been performed and a total of 179 carcinoma patients and 117 age-matched control subjects were included. All the participants in the study were recruited at the Department of Medical Oncology (University of Cagliari, Cagliari, Italy) from June 2011 to September 2014. 179. Results: Using the mentioned patient's groups in the cancer group, --patients affected by a different tumour types-- the frequencies observed have been non-cachectic: 58 (32.4%), pre-cachectic: 7 (3.9%) and cachectic: 114 (63.7%). Conclusion: It is concluded that CASC-IN can be satisfactorily used for both assessing cachectic and precachectic cancer patients. It constitutes the only available tool for the classification of pre-cachectic patients.

We investigate whether the geographic concentration of non-EU immigrants in the various Italian provinces affects labour tax avoidance (LTAV) practices adopted by firms located in the same provinces, as well as in the neighbouring provinces, and operating in construction and agriculture industries that mostly employ immigrants in Italy. For this purpose, we develop a LTAV proxy based on the financial accounting information of a sample of 993,606 firm-years, disseminated throughout the 108 Italian provinces, over the period 2008-2016. Our results, based on a Spatial Durbin Model panel regression, reveal a statistically significant positive association between the concentration of non-EU immigrants and LTAV at province level, as well as the presence of spillover effects among neighbouring provinces. Our findings are robust to several additional analyses, including instrumental variable estimations. Our study provides empirical support to previous structuralist or marginalization theories holding that socioeconomically marginalized groups, such as non-EU immigrants, are more likely to be involved in labour exploitation practices, which could underlie our LTAV outcomes. Furthermore, it supports the need for tax authorities to strengthen labour inspections, coordinated at national level, especially in those contexts where non-EU immigrants are mostly employed. On the other hand, a greater social integration, assistance, and recognition of rights of immigrants may help to alleviate their situation of weakness that makes them more vulnerable to LTAV practices. Finally, tackling LTAV, associated with the underemployment of immigrants, may prevent its negative effects for society arising from the reduction of public resources to sustain the social welfare and finance public goods and services.

Alterations in amino acid and protein metabolism particularly in skeletal muscle are a key feature of cancer that contributes to the cachexia syndrome. Thus, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. These changes are promoted by both hormonal alterations and inflammatory mediators released as a result of the systemic inflammatory response induced by the tumor. Other events, such as alterations in the rate of myogenesis/apoptosis and decreased regeneration potential also affect skeletal muscle in patients with cancer. Mitochondrial dysfunction also contributes to changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators either released by the tumor or by the patient's healthy cells are responsible for the activation of these catabolic processes that take place in skeletal muscle and in other tissues/organs, such as liver or adipose tissues. Indeed, white adipose tissue is also subject to extensive wasting and 'browning' of some of the white adipocytes into beige cells; therefore increasing the energetic inefficiency of the patient with cancer. Recently, an interest in the role of micromRNAs either free or transported into exosomes has been related to the events that take place in white adipose tissue during cancer cachexia.

This article examines the relationship between CEO characteristics and firm performance with a sample formed by the best performing CEOs in the world according to Harvard Business Review. The empirical analysis is based on descriptive statistics techniques and studies the universe of CEOs included in the 2016 ranking “The Best-Performing CEOs in the World” released by Harvard Business Review. Moreover, it addresses performance at various levels: financial performance, environmental, social and governance performance (ESG) and overall performance. The findings of the study show: 1) a strongly negative association between financial and ESG performance; 2) outsider CEOs outperform insider CEOs in overall performance; 3) CEOs with engineering degrees show significantly higher ESG performance; 4) CEOs with longer tenures in the firm present stronger financial performance though weaker ESG performance; and 5) the CEO’s country of origin emerges as an important driver to explain the different types of performance. Results in this field contradict the conventional wisdom of Anglo-Saxon CEOs as the best performers CEOs.

The aim of this article is to review the metabolic background of the cachectic syndrome and to analyze the recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia.The main changes associated with the development of this multiorganic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. Among the most promising approaches for the treatment of cachexia include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and antimyostatin peptides. The multitargeted approach seems essential in these treatments, which should include the combination of both nutritional support, drugs and a suitable program of physical exercise, in order to ameliorate both anorexia and the metabolic changes associated with cachexia. In addition, another very important aspect for the design of clinical trials for the treatment of cancer cachexia is to staging cancer patients in relation with the degree of cachexia, in order to start as early as possible, this triple approach in the course of the disease, even before weight loss can be detected.Cancer cachexia has two main components: anorexia and metabolic alterations and both have to be taken into consideration for the treatment of the syndrome.

Directive 2014/56/EU and Regulation (EU) No. 537/2014, which came into effect in June 2016, introduced the mandatory rotation of audit firms after a maximum period of 10 years with the same client. We conduct a cross‐European study with the aim of assessing whether long audit firm tenures are associated with lower levels of audit quality. The sample for the study is based on the constituents of the Standard & Poor's Europe 350 index for the years between 2009 and 2016, and we utilize three different sets of proxies for audit quality: discretionary accruals, differences between reported earnings and earnings benchmarks, and accounting restatements. The main result of the study finds that companies with more than 10 years of tenure with their auditors do not have a lower audit quality than other firms. In fact, this study provides some evidence of a higher audit quality for these firms. The results are robust to various checks. Therefore, if there does not seem to be a problem of a lack of audit quality associated with long audit firm tenures, the necessity of establishing a maximum tenure, as the new European regulation does, may be questioned.

This research analyses the convenience and consequences of the ANECA criteria for the assessment of the research performed by accounting academics in Spain. We focus on the level for the accreditation of catedrático de universidad, and the publication patterns and possibilities of the accounting scholars in Spain. We find that they have more difficulties for publication than their counterparts in adjacent fields of knowledge. Most of the accounting academics affiliated to Spanish institutions than have succeeded in publishing in the top international accounting journals co-authored their articles with foreign authors, mainly affiliated to USA or UK institutions, and/or focused their research on international setting and topics. The Spanish regulation for accreditation stresses this pattern. This situation may have serious consequences for the survival of the accounting discipline in Spain and for the research on topics focused on Spanish problems. Este trabajo analiza la conveniencia y consecuencias de los criterios de evaluación de la actividad investigadora en contabilidad establecidos por ANECA, concretándonos en los criterios para la acreditación de catedrático de universidad, así como el patrón y posibilidades de publicación de los académicos contables en España, Europa y a nivel mundial. Encontramos que los académicos del área contable tienen unas dificultades para publicar que son substancialmente superiores a las de los académicos de otras áreas de empresa. La mayor parte de los académicos afiliados a instituciones españolas que consiguen publicar en las principales revistas académicas contables recurren a co-autorías, principalmente estadounidenses y británicas, y a focalizar el contenido de sus trabajos en contextos y problemáticas no españolas. La normativa española de acreditación acentúa este comportamiento. Esta situación puede tener graves implicaciones para la supervivencia del área de conocimiento, el tratamiento de las temáticas y problemáticas específicamente ligadas al contexto español.

Silvia Busquets,1,2 Marta Castillejo,1 Queralt Jové,1 Baptiste Jude,3 Patricia Mejías,1 Francisco J López-Soriano,1,2 Josep M Argilés1,2 1Cancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; 2Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain; 3Laboratoire de Physiologie - EA 4324 ORPHY, IBSAM, Université de Bretagne Occidentale, Brest, FranceCorrespondence: Silvia BusquetsCancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, Barcelona, 08028, SpainTel +34-934021002Fax +34-934021559Email silviabusquets@ub.eduBackground: During cancer cachexia, both skeletal muscle and adipose tissue losses take place. The use of β 2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals.Methods: Rats were separated into two groups: controls (C) and tumour bearing (TB). TB group was further subdivided into four groups: untreated (saline as a vehicle), treated with Formoterol (TF) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with Dantrolene (TD) (5 mg/kg body weight in saline, subcutaneous (s.c.), daily), and double-treated treated (TFD) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and Dantrolene (5 mg/kg body weight, subcutaneous (s.c.), daily). 7 days after tumour transplantation, muscle weight, grip force, and total physical activity were specified in all experimental groups.Results: While formoterol had, as in previous studies, a very positive effect in reducing muscle weight loss, dantrolene had no effects, neither on skeletal muscle nor on any of the parameters studied. Finally, the combined treatment (formoterol and dantrolene) did not result in any significant benefit on the action of the β 2-agonist.Conclusion: It is concluded that, in the preclinical cachectic model used, no synergy exists between β 2-agonist treatment and the blockade of sarcoplasmic-calcium flow.Keywords: cancer cachexia, skeletal muscle, dantrolene, formoterol, calcium, ryanodine receptor 1

This paper reports an empirical analysis of the influence of e-commerce business practices on tax avoidance. Using a sample of European parent firms in the retail trade industry from 22 different countries, we find empirical evidence that e-commerce firms are significantly more tax avoidant than traditional firms. However, as the latter have increasingly sought to avoid paying taxes over the period studied, the gap between the two firm types has been reduced. Our results are robust to different specifications of tax avoidance, time, and sample selection criteria.

PurposeThis paper develops novel proxies for labour tax avoidance (LTAV) and tests their validity within a sample of 189 labour tax-avoidant offending firms (LTAOFs) accused of evading social security contributions (SOCs) by public authorities.Design/methodology/approachLTAV proxies are based on abnormal values of SOCs paid, reported in the income statements of a sample of 857,790 Spanish firm-years for the period 2001–2015, estimated through two-stage least square panel data regressions with firm fixed effects.FindingsThe results reveal that proxies specifically built to signal both conforming and non-conforming LTAV can provide evidence of abnormally low SOCs as expenses within the sample of LTAOFs. Furthermore, firm-specific financial variables as well as macroeconomic variables significantly influence LTAV.Research limitations/implicationsThis study could foster further research on the efficacy of the LTAV proxies and on the drivers and sustainability implications of LTAV for firms and their stakeholders in different socio-economic and institutional contexts.Practical implicationsThese LTAV proxies could integrate other methods applied to estimate the undeclared work and its trends. Furthermore, they may assist tax authorities to direct their inspections, detect labour tax evasion and then strengthen the social protection of the employees from employers' illegal exploitation practices, as well as reducing tax revenue shortfalls and related sustainability concerns in the social security systems.Originality/valueThis study proposes a novel methodology to examine LTAV and its determinants through accounting information. This methodology may support researchers to provide a more comprehensive picture of tax planning strategies pursued by companies, that include LTAV, and in this way integrate the extant mature literature on income tax avoidance.

Muscle wasting is associated with chronic diseases and cancer. Elucidation of the biological mechanism involved in the process of muscle mass loss and cachexia may help identify therapeutic targets. We hypothesized that l-carnitine treatment may differentially revert muscle fiber atrophy and other structural alterations in slow- and fast-twitch limb muscles of rats bearing the Yoshida ascites hepatoma. In soleus and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally) with and without treatment with l-carnitine (1 g/kg body weight for 7 days, intragastric), food intake, body and muscle weights, fiber typing and morphometry, morphological features, redox balance, autophagy and proteolytic, and signaling markers were explored. Levels of carnitine palmitoyl transferase were also measured in all the study muscles. l-Carnitine treatment ameliorated the atrophy of both slow- and fast-twitch fibers (gastrocnemius particularly), muscle structural alterations (both muscles), and attenuated oxidative stress, proteolytic and signaling markers (gastrocnemius). Despite that carnitine palmitoyl transferase-1 levels increased in both muscle types in a similar fashion, l-carnitine ameliorated muscle atrophy and proteolysis in a muscle-specific manner in cancer-induced cachexia. These data reveal the need to study muscles of different fiber type composition and function to better understand whereby l-carnitine exerts its beneficial effects on the myofibers in muscle wasting processes. These findings also have potential clinical implications, since combinations of various exercise and muscle training modalities with l-carnitine should be specifically targeted for the muscle groups to be trained. The current research has been supported by Instituto de Salud Carlos‐III, contract grant numbers, CIBERES, FIS 14/00713 (FEDER), FIS 18/00075 (FEDER), Spanish Ministry of Science and Innovation, contract grant number SAF 2011–26091, Spanish Respiratory Society (SEPAR), contract grant numbers, SEPAR 2016, SEPAR 2018, Catalan Foundation of Pulmonology (FUCAP), contract grant numbers, FUCAP 2016.

Despite evidence suggesting that specialised knowledge should be more relevant than generic knowledge to explain different levels of audit quality across individual auditors, no study to date has addressed the respective impacts of the industry-specific and the generic audit experience of audit partners on the quality of audit services. Our study investigates this issue in the Spanish audit market. We proxy audit quality by discretionary accruals and by the opinion of the audit report, and differentiate among client-specific experience, industry-specific experience and generic audit experience of individual auditors. As expected, our results show significantly higher audit quality when the client is audited by a partner with stronger industry-specific audit experience. Furthermore, we observe that neither client-specific experience nor generic audit experience of audit partners are significant determinants of the quality of audit services provided by these auditors. These results may have some interesting implications for audit firms. Therefore, whereas some prior studies on the related issue of industry specialization point out that specialised knowledge is more relevant than generic knowledge to explain the quality of audit services, our findings suggest that specialised knowledge is, in fact, the only type of knowledge that seems to matter. A pesar de la evidencia que sugiere que el conocimiento especializado debería resultar más relevante que el genérico para explicar diferentes niveles de calidad de auditoría asociados a los auditores individuales, ningún estudio hasta la fecha ha abordado el posible impacto diferencial de la experiencia genérica y específica en la calidad de los servicios de auditoría. Nuestro estudio investiga esta cuestión en el mercado de auditoría español. Aproximamos la calidad de la auditoría a partir de los ajustes de devengo discrecionales y la opinión del informe de auditoría; diferenciando entre experiencia específica con el propio cliente, experiencia sectorial y experiencia de auditoría genérica. Como se esperaba, los resultados muestran una mayor calidad de auditoría cuando el cliente es auditado por un socio con mayor experiencia en el sector de actividad del cliente. También observamos que ni la experiencia específica con el propio cliente, ni la experiencia genérica de auditoría del socio auditor son determinantes significativos de la calidad de los servicios de auditoría. Por otro lado, mientras que algunos estudios previos señalan que el conocimiento especializado resulta más relevante que el genérico para explicar la calidad de los servicios de auditoría, este trabajo sugiere que el conocimiento especializado es, de hecho, el único tipo de conocimiento que resulta relevante. Estos resultados pueden tener implicaciones interesantes para las firmas de auditoría

On May 27, 2014, Regulation (EU) No 537/2014 was published in the Official Journal of the European Union. Aiming to enhance audit quality, the new regulation establishes important limitations to the selling of non-audit services by the audit firm to audit clients and a maximum tenure of ten years with the audit firm. However, it should be noted that the extant research has not consistently supported that non-audit services or long tenures impair the quality of audits. This research studies whether these provisions have been empirically associated with reduced audit quality for Spain. Because of its low litigation risk, the potentially negative impact of both non-audit services and tenure on audit quality should be clearly observed in the Spanish audit market. Nevertheless, we do not find significantly lower levels of audit quality associated with either non-audit services or long audit tenures. However, these results are conditional on the validity of using abnormal accruals to measure audit quality.

Alterations in amino acid protein metabolism are a key feature of the cancer cachexia syndrome. These changes -induced by both hormonal changes (that affect insulin sensitivity) and inflammatory mediators- are present in skeletal muscle influencing both, amino acid uptake and protein synthesis. In addition, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. Changes in the rate of myogenesis/apoptosis also determine skeletal muscle mass during cancer cachexia. Indeed, a decreased skeletal muscle regeneration capacity is observed together with an increased rate of cell death, resulting in muscle wasting. Mitochondrial dysfunction also results in changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators -either released by the tumor or by healthy cells of the cancer patient- are responsible for the activation of these catabolic processes that take place in skeletal muscle.

Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 tumor-bearing mice, stress-induced autophagy inhibition was unable to rescue the loss of muscle mass and worsened muscle morphology. Treating C26-bearing mice with formoterol, a selective β2-agonist, muscle sparing was paralleled by reduced static autophagy markers, although the flux was maintained. Conversely, the stimulation of muscle autophagy exacerbated muscle atrophy in tumor-bearing mice. TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes. Excessive autophagy might impair mitochondrial function through mitophagy. Consistently, tumor-induced mitochondrial dysfunction was detected by reduced ex vivo muscle fiber respiration. Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting.

We develop new transaction management (TRM) proxies, to find empirical evidence of the strategic management of accounting transactions, aiming to carry out money laundering activities, within a sample of 355 firms controlled by Italian Mafias. Our results reveal that, using a cluster analysis, Mafia-controlled firms can be classified into two different groups corresponding to real firms and shell firms, based on specific assumptions on their distinctive peculiarities. Importantly, our regression estimations provide evidence of different TRM practices of these firms, which may be linked to specific money laundering activities. Finally, the seizure of Mafia-controlled firms and their assignment to legal administrators only have a significant impact on TRM within Mafia-controlled shell firms, whereas the null impact on TRM, within Mafia-controlled real firms, casts doubt on the ability of legal administrators to completely deter money laundering. This study proposes new TRM proxies, based on the nature of the expenditure transaction, which could be used by authorities as accounting red flags of money laundering activities. Furthermore, this study may support critical arguments against the orthodox view of the anti-money laundering role of accounting and the suitability of traditional TRM proxies to depict practices within firms sharing common traits with Mafia-controlled firms. Indeed, these firms may engage in TRM for illicit and/or opportunistic purposes, when the external scrutiny is weak, their financial statements are irrelevant for trading with stakeholders, because of competitive advantages or dominant market positions, and they can count on colluded actors as counterparties of money laundering transactions.

Codes of good practices provide a soft alternative to the hard legislation approach to corporate governance. These codes include a set of recommendations that companies are expected to follow in order to enhance governance structures and practices. Some of these recommendations specifically aim to improve the effectiveness of the audit committee. We investigate the relationship between the level of compliance with recommendations on the audit committee of the Spanish Unified Code and financial reporting quality, as measured by discretionary accruals and by the opinion of the audit report. We use a sample of companies listed in the Spanish stock market for the years between 2007 and 2013. Results show a strong and positive relationship between the level of compliance with recommendations and the quality of financial reporting. We also report significant results for some specific recommendations. These results are robust to various checks. Therefore, the level of compliance with recommendations on the audit committee might provide a feasible and reliable indicator of the quality of financial reports released by the company.

Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species. Myostatin/activin inhibition reverses skeletal muscle loss and prolongs survival of tumor-bearing animals. The aim of this investigation was to evaluate the effects of a combination of the soluble myostatin receptor ActRIIB (sActRIIB) and the β2-agonist formoterol in the cachectic Lewis lung carcinoma model. The combination of formoterol and sActRIIB was extremely effective in reversing muscle wasting associated with experimental cancer cachexia in mice. Muscle weights from tumor-bearing animals were completely recovered following treatment and this was also reflected in the measured grip strength. This combination increased food intake in both control and tumor-bearing animals. The double treatment also prolonged survival significantly without affecting the weight and growth of the primary tumor. In addition, it significantly reduced the number of metastasis. Concerning the mechanisms for the preservation of muscle mass during cachexia, the effects of formoterol and sActRIIB seemed to be additive, since formoterol reduced the rate of protein degradation (as measured in vitro as tyrosine release, using incubated isolated individual muscles) while sActRIIB only affected protein synthesis (as measured in vivo using tritiated phenylalanine). Formoterol also increased the rate of protein synthesis and this seemed to be favored by the presence of sActRIIB. Combining formoterol and sActRIIB seemed to be a very promising treatment for experimental cancer cachexia. Further studies in human patients are necessary and may lead to a highly effective treatment option for muscle wasting associated with cancer.

We examine the effects of Mafia infiltration on public procurement performance, based on a sample of 68,063 public work contracts (PWC) awarded by Italian municipalities over the period 2012–2017, of which 687 are identified as Mafia-infiltrated, either because of being awarded by municipal councils subsequently dissolved due to Mafia infiltration, or because of being won by Mafia-owned firms. Our results reveal that Mafia infiltration is positively associated with number of submitted bids, awarding rebates and execution cost overruns, whereas it is negatively associated with delivery delays for PWC. The effect of Mafia infiltration on execution cost overruns and the probability of their occurrence is weaker for larger PWC, and the elections of the new municipal councils, after the dissolution of the previous ones, do not significantly influence the performance of PWC. Our findings suggest the presence of collusive schemes among bidding firms within the Mafia network and provide new insights for the implementation of more sound policies to tackle practices associated with Mafia infiltration in public procurement.

Cachexia is a systemic condition that occurs during many neoplastic diseases, such as cancer. Cachexia in cancer is characterized by loss of body weight and muscle and by adipose tissue wasting and systemic inflammation. Cancer cachexia is often associated with anorexia and increased energy expenditure. Even though the cachectic condition severely affects skeletal muscle, a tissue that accounts for ~40% of total body weight, it represents a multi-organ syndrome that involves tissues and organs such as white adipose tissue, brown adipose tissue, bone, brain, liver, gut and heart. Indeed, evidence suggests that non-muscle tissues and organs, as well as tumour tissues, secrete soluble factors that act on skeletal muscle to promote wasting. In addition, muscle tissue also releases various factors that can interact with the metabolism of other tissues during cancer. In this Review, we examine the effect of non-muscle tissues and inter-tissue communication in cancer cachexia and discuss studies aimed at developing novel therapeutic strategies for the condition. Cachexia is a multi-organ syndrome associated with cancer. In this Review, Josep M. Argiles and colleagues discuss the role of different tissues and organs in cancer cachexia and examine studies that investigate the development of novel therapeutics for the condition.

Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Beta-adrenoceptors attenuate muscle wasting. We hypothesized that specific muscle atrophy signaling pathways and altered metabolism may be attenuated in cancer cachectic animals receiving treatment with the beta2 agonist formoterol. In diaphragm and gastrocnemius of tumor-bearing rats (intraperitoneal inoculum, 108 AH-130 Yoshida ascites hepatoma cells, 7-day study period) with and without treatment with formoterol (0.3 mg/kg body weight/day/7days, subcutaneous), atrophy signaling pathways (NF-κB, MAPK, FoxO), proteolytic markers (ligases, proteasome, ubiquitination), autophagy markers (p62, beclin-1, LC3), myostatin, apoptosis, muscle metabolism markers, and muscle structure features were analyzed (immunoblotting, immunohistochemistry). In diaphragm and gastrocnemius of cancer cachectic rats, fiber sizes were reduced, levels of structural alterations, atrophy signaling pathways, proteasome content, protein ubiquitination, autophagy, and myostatin were increased, while those of regenerative and metabolic markers (myoD, mTOR, AKT, and PGC-1alpha) were decreased. Formoterol treatment attenuated such alterations in both muscles. Muscle wasting in this rat model of cancer-induced cachexia was characterized by induction of significant structural alterations, atrophy signaling pathways, proteasome activity, apoptotic and autophagy markers, and myostatin, along with a significant decline in the expression of muscle regenerative and metabolic markers. Treatment of the cachectic rats with formoterol partly attenuated the structural alterations and atrophy signaling, while improving other molecular perturbations similarly in both respiratory and limb muscles. The results reported in this study have relevant therapeutic implications as they showed beneficial effects of the beta2 agonist formoterol in the cachectic muscles through several key biological pathways. The authors are thankful to Dr. Ester Puig-Vilanova for her technical assistance with part of the biological experiments and to Mr. Xavier Duran for his support with all the statistical analyses and study design. The current research has been supported by Instituto de Salud Carlos-III, contract grant numbers, CIBERES, FIS 14/00713 (FEDER); Spanish Ministry of Science and Innovation, contract grant number SAF 2011-26091; Spanish Respiratory Society (SEPAR), contract grant numbers, SEPAR 2013 and SEPAR 2016; Catalan Foundation of Pulmonology (FUCAP), contract grant numbers, FUCAP 2011, FUCAP 2012, and 2016.

Background: Type 2 Diabetes Mellitus affects more than 350 million people worldwide. This metabolic disorder is characterized by insulin resistance, β-cell dysfunction and elevated hepatic glucose output. Patients with diabetes are hospitalized frequently (3-fold greater) and with longer admissions (30% longer) than the non-diabetic subjects. The aim of the study was to investigate the impact of bed rest on the metabolic changes in type II diabetes mellitus, with particular interest in skeletal muscle mass and function and metabolism. Methods: 13wk old male Zucker diabetic fatty (ZDF) rats were randomly divided into two groups: control (ZDF-Con) and cage-immobilized animals (ZDF-Cage) for 28 consecutive days in a space-restricted cage. Results: The Area Under the Curve (AUC) values for plasma glucose concentration in ZDF-Cage rats were significantly increased (approximately 4-fold as compared with ZDF-Con rats). GLUT4 gene expression in red soleus muscle of ZDF-Cage animals was reduced 2.5-fold in comparison with ZDF–Con rats. Although no apparent changes were observed either in fasting plasma glucose or insulin levels, a trend towards an increase in the HOMA-IR index and decreased levels of plasma adiponectin (-30%) were observed in ZDF-Cage animals. Moreover, ZDF-Cage rats did not lose muscle mass and force but performed a reduced total physical activity level (-22%). Conclusions: The present study results suggests that 28 days of immobilization --in a space-restriction model-- significantly impaired glucose tolerance with concomitant reduced plasmatic adiponectin levels and GLUT-4 expression in soleus muscle of type 2 diabetic rats.

Background L-Leu and its metabolite β-hydroxy-β-methylbutyrate (HMB) stimulate muscle protein synthesis enhancing the phosphorylation of proteins that regulate anabolic signalling pathways. Alterations in these pathways are observed in many catabolic diseases, and HMB and L-Leu have proven their anabolic effects in in vivo and in vitro models. The aim of this study was to compare the anabolic effects of L-Leu and HMB in myotubes grown in the absence of any catabolic stimuli. Methods Studies were conducted in vitro using rat L6 myotubes under normal growth conditions (non-involving L-Leu-deprived conditions). Protein synthesis and mechanistic target of rapamycin signalling pathway were determined. Results Only HMB was able to increase protein synthesis through a mechanism that involves the phosphorylation of the mechanistic target of rapamycin as well as its downstream elements, pS6 kinase, 4E binding protein-1, and eIF4E. HMB was significantly more effective than L-Leu in promoting these effects through an activation of protein kinase B/Akt. Because the conversion of L-Leu to HMB is limited in muscle, L6 cells were transfected with a plasmid that codes for α-keto isocaproate dioxygenase, the key enzyme involved in the catabolic conversion of α-keto isocaproate into HMB. In these transfected cells, L-Leu was able to promote protein synthesis and mechanistic target of rapamycin regulated pathway activation equally to HMB. Additionally, these effects of leucine were reverted to a normal state by mesotrione, a specific inhibitor of α-keto isocaproate dioxygenase. Conclusion Our results suggest that HMB is an active L-Leu metabolite able to maximize protein synthesis in skeletal muscle under conditions, in which no amino acid deprivation occurred. It may be proposed that supplementation with HMB may be very useful to stimulate protein synthesis in wasting conditions associated with chronic diseases, such as cancer or chronic heart failure.

Background The effectiveness of drugs aimed at counteracting cancer cachexia is generally tested in pre-clinical rodent models, where only the tumour-induced alterations are taken into account, excluding the co-presence of anti-tumour molecules that could worsen the scenario and/or interfere with the treatment. Methods The aim of the present investigation has been to assess the efficacy of a multifactorial treatment, including formoterol and megestrol acetate, in cachectic tumour-bearing rats (Yoshida AH-130, a highly cachectic tumour) undergoing chemotherapy (sorafenib). Results Treatment of cachectic tumour-bearing rats with sorafenib (90 mg/kg) causes an important decrease in tumour cell content due to both reduced cell proliferation and increased apoptosis. As a consequence, animal survival significantly improves, while cachexia occurrence persists. Multi-factorial treatment using both formoterol and megestrol acetate is highly effective in preventing muscle wasting and has more powerful effects than the single formoterol administration. In addition, both physical activity and grip strength are significantly improved as compared with the untreated tumour-bearing animals. The effects of the multi-factorial treatment include increased food intake (likely due to megestrol acetate) and decreased protein degradation, as shown by the reduced expression of genes associated with both proteasome and calpain proteolytic systems. Conclusions The combination of the two drugs proved to be a promising strategy for treating cancer cachexia in a pre-clinical setting that better resembles the human condition, thus providing a strong rationale for the use of such combination in clinical trials involving cachectic cancer patients.