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Abstract Background Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. Methods Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions. Results Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. Conclusions In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.

Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, small vessel, necrotizing vasculitis. The disease is mainly characterized by hypereosinophilia and asthma with frequent sinonasal involvement, although multiple organs can be affected, including the heart, lungs, skin, gastrointestinal tract, kidneys, and nervous system. IL-5 production is pathogenetically central for the development of the disease by promoting proliferation, transvascular migration and functional activation of eosinophils. The degree of blood and tissue eosinophilia appears to be associated with disease pathogenesis and eosinophil depletion represents a promising treatment approach for EGPA. We prospectively evaluated the efficacy and safety of a low dose (100 mg q4w), 12-month course of mepolizumab, an anti-IL-5 monoclonal antibody, in eight patients with severe asthma and active EGPA. Patients were recruited by the tertiary care center of Clinical Immunology and Allergy, University of Naples Federico II. The following outcomes were assessed before (T0), and after 6 (T6) and 12 months (T12) of mepolizumab treatment: Birmingham Vasculitis Activity Score (BVAS), prednisone intake, Sino-Nasal Outcome Test (SNOT-22), Total Endoscopic Polyp Score (TENPS), Asthma Control Test (ACT), Forced Expiratory Volume one second (FEV1)%, blood eosinophilia. BVAS score significantly decreased showing a sharp reduction in disease activity score. Clinical improvements in terms of sinonasal scores and asthma symptoms were observed, in parallel with a drastic drop in eosinophil blood count. Prednisone intake was significantly reduced. In two patients, asthma exacerbations led to discontinuation in mepolizumab therapy after 6 and 12 months despite BVAS reduction. Mepolizumab treatment was well tolerated, and no severe adverse drug effects were registered. In conclusion, our 12-month real-life study suggests that mepolizumab may be beneficial and safe in active EGPA patients by improving disease activity score, sinonasal and asthma outcomes while reducing the burden of prednisone intake.

My intention in this research is to focus on the idea of spiritual crisis in human rights arena. The topic I shall be discussing concerns a basic set of issues dealing with the purpose of human rights, their moral foundation and their ultimate metaphysical ground. Simply put I shall be asking whether there is something special in human beings which entitles them to rights. Some arguments such as human agency, dignity and natural law tend to be quite abstract. It could therefore be tempting to assume that the issue, being of not much practical importance, is not relevant. But this would be a rush assumption because determining the foundation of human rights means determining the very legitimacy of human rights themselves in the international arena. I will consider Ignatieff’s pragmatic point of view that can be summed up with a catch phrase: “without the Holocaust no Declaration, because of the Holocaust, no unconditional faith in the Declaration either” and Stackhouse’s religious one developed in Religion and Human Rights: a Theological Apologetic. My purpose is to analyse both Ignatieff’s view, that avoids contentious religious ground for human rights and offers a secular ground designed with the idea of human agency, and Max Stackhouse who, instead, defends the idea of a theological ethic as religious ground for human rights. First of all, through this analysis I aim at pointing out that while on the one hand the respect for our fellow human beings needs a reverential attitude and our commitment to protect our species needs to be sustained by some faith; on the other hand grounding human rights in religion is extremely dangerous and may imply violent clashes between different religious faiths. Secondly, I also aim at criticizing Ignatieff’s view because a defence of human rights as pragmatic instruments on pragmatic grounds seems to be too weak and human rights regime needs moral and metaphysical foundations to be universally recognized and implemented. Thirdly and ultimately, using Rawls’s concept of overlapping consensus I aim at showing the unecessity to agree upon a “single foundation”. A single foundation risks to be authoritative, whereas, what a human rights regime relies on is a plural foundations. If we arrive at respecting human rights on a plurality of grounds, then we are making them more broadly acceptable to people. If we publicly defend human rights for a plurality of reasons, we are rightly proving that there is no “proper” metaphysical foundation. A good reason why we do not need to ground human rights in any particular metaphysics can be that they are already grounded in many metaphysics and can already derive sustenance from many sources. Hence, it would be worthwhile and wise to welcome a plurality of nonexclusive claims concerning the ways in which human rights can legitimately be grounded. Human agency, human dignity, equal creation are, for instance, some examples of different foundations that are not mutually exclusive. هدف من در این تحقیق تمرکز بر ایدة بحران معنوی در عرصه حقوق بشر است. موضوعی که من آن را مورد بحث قرار می­دهم به مجموعه­ای اساسی از مسائلی مرتبط می­شود که به هدف حقوق بشر، پایه اخلاقی آن­ها و زمینه متافیزیکی غایی آن­ها مربوط می­شود. به شکل ساده تر این پرسش را مطرح می­کنم که آیا در افراد نوع بشر چیز خاصی وجود دارد که آن­ها را مستحق داشتن حق می­کند؟ برخی از استدلال­ها مانند عامل انسان، کرامت و قانون طبیعی کاملا انتزاعی هستند. بنابراین می­توان چنین فرض کرد که چون مسئله اهمیت کاربردی زیادی ندارد، این استدلالات مرتبط نیستند. اما این فرض کمی عجولانه است، زیرا تعیین پایه و اساس حقوق بشر به معنی تعیین مشروعیت خودِ حقوق بشر در عرصة بین­المللی است. من دیدگاه عملگرا ایگناتیف را که می­توان به صورت یک جمله کلیدی خلاصه کرد در نظر می­گیرم: «بدون هولوکاست اعلامیه حقوق بشر وجود نداشت. به خاطر هولوکاست، هیچ اعتقاد بی قید و شرطی در این اعلامیه وجود ندارد.» و دین داری استاک هاوس در دین و حقوق بشر توسعه یافته است: متکلمان دینی. هدف من این است که هر دو دیدگاه را بررسی کنم. هم دیدگاه ایگناتیف که از پرداختن به زمینه­های مذهبیِ حقوق بشر دوری می­کند و یک دیدگاه با پایه­های سکولار با ایده عاملیت انسان ارائه می­دهد و هم دیدگاه مکس استاک هاوس که بر خلاف ایگناتیف از اخلاقی دینی به عنوان پایه­های حقوق بشر دفاع می­کند. اول از همه از طریق این تجزیه و تحلیل، قصد دارم اشاره کنم در حالی که از یک سو احترام به هم نوعان ما نیازمند یک رویکرد محبت آمیز است و تعهد ما به حفظ نوع بشر نیازمند تقویت توسط ایمان دارد؛ از سوی دیگر پایه گذاری حقوق بشر در دین بسیار خطرناک است و ممکن است درگیری­های خشونت آمیز میان مذاهب مختلف به وجود آورد. دوماً به انتقاد از دیدگاه ایگناتیف می­پردازم، چرا که دفاع از حقوق بشر به عنوان ابزار عملگرایانه، در زمینه­های عملی بسیار ضعیف است و نظام حقوق بشر نیازمند مبانی اخلاقی و متافیزیکی است که به طور جهانی شناخته شده باشد و به اجرا درآمده باشند. سوماً و در نهایت با استفاده از مفهوم رالز در خصوص همپوشانی اجماع، قصد من نشان دادن عدم نیاز به توافق بر سر «بنیان­های واحد» می­باشد. در نظر گرفتن یک بنیان واحد توانا و معتبر برای حقوق بشر، ریسک پذیر است. در حالی که یک رژیم حقوق بشری بر بنیان­های چندگانه استوار است. پذیرش حقوق بشر با بنیان­های چندگانه توسط ما به پذیرش وسیع تر آن توسط مردم کمک می­نماید. اگر به علت گوناگونی به طور عمومی از حقوق بشر دفاع کنیم، به درستی ثابت می­کنیم که هیچ پایه متافیزیکی مناسبی وجود ندارد. دلیل خوبی برای آنکه که چرا ما نیازمند زمینه­های حقوق بشری در هر متافیزیک خاص نیستیم می­تواند این باشد که آن­ها هم اکنون نیز به بسیاری از متافیزیک­ها متکی هستند و در حال حاضر می­توانند از منابع بیشتری بهره ببرند. از این رو ارزشمند و عاقلانه است که از ادعاهای غیر انحصاری متکثر مرتبط با راه­هایی که حقوق بشر [به واسطة آن­­ها] به طور قانونی پایه گذاری می­شود، استقبال کرد. برای مثال عاملیت انسان، کرامت انسانی، ایجاد برابری، نمونه­هایی از مبانی مختلفی هستند که منحصر به فرد و ناسازگار با دیگری نیستند.

Background: the aim was to verify the association between Major Depressive Disorders (MDD) and the risk of premature death in people with oncological diseases, and to collect evidence about the causality of a possible association from a longitudinal perspective. Design and Methods: it is a cohort study lasting 9 months, involving people with solid or hematologic cancers. The assessment was conducted by an ad hoc form to collect socio-demographic and clinical-oncological data, the PHQ-9 to screen MDD (cut-off ≥10) and the SF-12 to evaluate HRQoL. Relative Risk (RR) of early death between MDD exposed and not-exposed and Kaplan-Meier survival were carried out. Results: people exposed to MDD during the follow-up were 107/263 (40.7%). Among them, 36 deceased during the observation period. Overtime, having MDD and death’ occurrence showed a strong association (RR=2.15; 95% CI (1.10-4.20); χ²=5.224, p=0.0022), confirmed by Kaplan-Meier survival analysis (χ²=4.357, p=0.037). Among people who died, there was not any association between MDD, age, gender, HRQoL, cancer stage and site. Conclusions: the study confirms the association between MDD and early death in people with cancer. The absence of any association between the onset of MDD and advanced stage of cancer may suggest that it could be due to the consequences of MDD in worsening the clinical conditions related to cancer. The findings point out the relevance of MDD’ early detention among people with cancer.

AIAPP - Italian Association of Landscape Architecture in recent years has planned a number of activities and initiatives at national level which path towards the 53 th World Congress of IFLA (International Federation of Landscape Architects). Theme of the World Congress to be held in Turin in April 2016, and that AIAPP as a member of Italian IFLA is called to organize, is the Landscape Tasting (http://www.ifla2016.com). These activities highlight the two national conferences on the subject Landscape and Agricultures (Landscape and Agricultures, November 28, 2014 in Lecce, Landscape and Agricultures 2.0, June 26, 2014 in Milan), which had the task of exploring how the landscape design can be placed with respect to different forms of agriculture which today concern the Italian territory. The variation in the plural of the word agriculture has in fact the precise purpose of indicating and integrate all the multiple areas, approaches and objectives that the landscape project can and must confront, transform and resolve, especially in light of the nowdays technical, socio-economic and cultural changes.

The Sardinia Landscape Plan (PPR) is the first unitary Plan concerning the regional landscape. This is also the first time that a Landscape Plan involves the whole regional territory in a single process of knowledge and management of strategic resources. Moreover, the PPR represents a new experience thanks to its innovative approach towards the urban development.

The new regional landscape plan comes as the implementation of the PIT (Territorial Address Plan of Region) as pursuant to art. 143 of the Codice dei beni culturali e del paesaggio and to art. 33 of L.R. n. 1/2005 Norme per il Governo del Territorio (Rules for the Government of the territory). The plan consists of three main parts: Plan Document, Discipline landscape, knowledge chart.

The Sardinia Landscape Plan (PPR) is the first unitary Plan concerning the regional landscape. This is also the first time that a Landscape Plan involves the whole regional territory in a single process of knowledge and management of strategic resources. Moreover, the PPR represents a new experience thanks to its innovative approach towards the urban development.

Since its foundation the Regione Toscana (Tuscan Region) has chosen to integrate both the protection and conservation of landscape within its territorial planning and to build a “chain” among the different planning levels (regional, provincial and urban/municipal). It is in this context that the new regional landscape plan, which is part of the PIT (Territorial Address Plan of Region), is born. Thanks to a specific agreement between the Ministry and the Regione Toscana, the hierarchical process established by the “Codice dei Beni Culturali e del Paesaggio” has been overcome as it is acknowledged that all levels of planning contribute and are responsible for the implementation of the landscaping plan, thereby the cohesion, the typical model of regional governance is respected.

Accessibility is a complex issue that also concerns the fruition of the public space of the city, but in Italy it is presented mainly as yet another aseptic technical-normative requisite to satisfy. The UdR FAL of DIDA born with the intention to widen this term and to spread a new cultural approach in which “accessibility habitat” is transformed into “a great resource for the collective human empowerment, to make it viable, safe and cohesive local communities, for the development of the architectural and landscape heritage”. Or rather “it indicates the ability of a habitat to ensure an independent life to every person, regardless of age, gender, cultural background and the physical, sensory and cognitive”.

Although the risk of acquisition of hepatitis B or hepatitis C virus through blood products has considerably reduced since the last decade, some infected patients are candidates to stem cell transplantation. Others may have no alternative than an infected donor. In all these cases, recipients of transplant are prone to short and long term liver complications. The evolution of liver tests under chemotherapy before transplant may give useful information to anticipate on the risk of hepatitis reactivation after transplant, both for HBv and HCv. More than sixty percent of the patients who are HBsAg-positive before transplant reactivate after transplant, and 3% develop acute severe liver failure. Because both viral replication and immune reconstitution are the key factors for reactivation, it is crucial to closely follow liver function tests and viral load during the first months of transplant, and to pay a special attention in slowly tapering the immunosuppression in these patients. Lamivudine reduces HBv viremia, but favors the emergence of HBv polymerase gene mutants and should be individually discussed. Both in case of HBv or HCv hepatitis reactivation with ALT > 10N concomitantly to an increase in viral load at time of immune reconstitution, steroids should be given. In case there is no alternative than a HBv or HCv positive geno-identical donor, the risk of viral hepatitis, including acute liver failure and late complications, should be balanced with the benefit of transplant in a given situation.