Does the Pharmaceutical Sector Have a Coresponsibility for the Human Right to Health?

The highest attainable standard of health is a fundamental human right, which has been part of international law since 1948. States and their institutions are the primary duty bearers responsible for ensuring that human rights are respected, protected, and fulfilled. However, more recently it has been argued that pharmaceutical companies have a coresponsibility to fulfill the human right to health. Most prominently, this coresponsibility has been expressed in the United Nations (UN) Millennium Goal 8 Target 4. “In cooperation with pharmaceutical companies, provide access to affordable essential drugs in developing countries.

Predictive value of CA 125 and CA 72-4 in ovarian borderline tumors

Background: The aim of this study was to assess the prognostic value of cancer antigen (CA) 125 and CA 72-4 in patients with ovarian borderline tumor (BOT). Methods: All women diagnosed and treated for BOT at our institution between 1981 and 2008 were included into this retrospective study (n=101). Preoperatively collected serum samples were analyzed for CA 125 (Architect, Abbott and Elecsys, Roche) and CA 724 (Elecsys, Roche) with reference to clinical data and compared to healthy women (n=109) and ovarian cancer patients (n=130). Results: With a median of 34.7 U/mL (range 18.1-385.0 U/mL) for CA 125 and 2.3 U/mL (range 0.2-277.0 U/mL) for CA 72-4, serum tumor markers in BOT patients were significantly elevated as compared to healthy women with a median CA 125 of 13.5 U/mL (range 4.0-49.7 U/mL) and median CA 72-4 of 0.8 U/mL (range 0.2-20.6 U/mL). In addition, there was a significant difference compared with ovarian cancer patients who showed a median CA 125 of 401.5 U/mL (range 12.5-35,813 U/mL), but no difference was observed for CA 72-4 (median 3.9 U/mL, range 0.3-10,068 U/mL). Patients with a pT1a tumor stage had significantly lower values of CA 125 but not of CA 72-4 compared with individuals with higher tumor stages (median CA 125 29.9 U/mL for pT1a vs. 50.9 U/mL for) pT1a; p=0.014). There was a trend for increased concentrations of CA 125 but not of CA 72-4 in the presence of ascites, endometriosis or peritoneal implants at primary diagnosis. With respect to the prognostic value of CA 125 or CA 72-4, CA 125 was significantly higher at primary diagnosis in patients who later developed recurrence (251.0 U/mL vs. 34.65 U/mL, p=0.012). Conclusions: Serum CA 125 and CA 72-4 concentrations in BOT patients differ from healthy controls and patients with ovarian cancer. CA 125, but not CA 724, at primary diagnosis correlates with tumor stage and tends to be increased in the presence of ascites, endometriosis or peritoneal implants. Moreover, CA 125 at primary diagnosis appears to have prognostic value for recurrence. Clin Chem Lab Med 2009; 47:537-42

Palaeodietary traits of large mammals from the middle Miocene of Gracanica (Bugojno Basin, Bosnia-Herzegovina)

Recent excavations at the Gracanica coal mine (Bugojno Basin, Bosnia-Herzegovina) have unearthed numerous skeletal parts of fossil vertebrates, including a noteworthy collection of mammalian remains. Previous palaeoecological investigations of the Dinarides Lake System were established using stratigraphical, palaeofloral, and malacological data. However, large mammal remains have so far not been used to reconstruct the terrestrial palaeoenvironment of this important fossil ecosystem. Here, the palaeodietary preferences of large mammals were investigated, using a multiproxy approach by employing dental microwear and dental mesowear analysis, in order to provide new perspectives on the terrestrial palaeoecology of the Dinarides Lake System. The dental microwear of all available adult mammalian teeth was analysed. Dental mesowear analysis was employed for ungulate and proboscidean taxa, using mesowear scores and mesowear angles, respectively. The analysis reveals the presence of browsing, "dirty browsing", and mixed-feeding herbivorous taxa, with seasonal fruit, or even grass intake. Additionally, the analysis of the carnivores suggests the presence of hyaena- and cheetah-like hypercarnivores, as well as generalists. The palaeodietary traits of the fossil mammals suggest a closed canopy-like environment, which is supported by the fossil plant assemblage. Palaeopalynological data confirm the omnipresence of fleshy fruit-bearing plants, herbaceous taxa, as well as grasses, which justifies the seasonal fruit browsing, the common "dirty browsing", and the occasional grazing behaviour visualized for some of the fossil mammals from Gracanica.Peer reviewe

The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses

Background: Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) improves diagnostic accuracy. Methods: We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma: n = 78, leimyoma: n = 66, endometriosis: n = 52, functional ovarian cysts: n = 79, other: n = 10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage 1: 22, II: 15, III: 78, IV: 10). CA 125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally. Results: The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA 125 alone was not significantly different to HE4 alone in premenopausal (CA 125: 86.7, HE4(a): 82.6, HE4(e): 81.6% p > 0.05) but significantly different in postmenopausal {[}CA125: 93.4 vs. HE4(a): 88.3 p = 0.023 and vs. HE4(e): 87.8% p=0.012] patients. For stage I OC, HE4 as a single marker was superior to CA 125, which was the best single marker in stage H-IV. The combination of CA 125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses {[}CA 125: 70.9, HE4(a): 67.4, HE4(e): 66.0, ROMA(a): 76.6 and ROMA(e): 74.5%], especially in stage I OC {[}CA 125: 27.3, HE4(a): 40.9, HE4(e): 40.9, ROMA(a): 45.5 and ROMA(e): 45.5%]. Conclusions: CA 125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA 125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC

Emotion, deliberation, and the skill model of virtuous agency

A recent skeptical challenge denies deliberation is essential to virtuous agency: what looks like genuine deliberation is just a post hoc rationalization of a decision already made by automatic mechanisms (Haidt 2001; Doris 2015). Annas’s account of virtue seems well-equipped to respond: by modeling virtue on skills, she can agree that virtuous actions are deliberation-free while insisting that their development requires significant thought. But Annas’s proposal is flawed: it over-intellectualizes deliberation’s developmental role and under-intellectualizes its significance once virtue is acquired. Doing better requires paying attention to a distinctive form of anxiety—one that functions to engage deliberation in the face of decisions that automatic mechanisms alone cannot resolve

Evolutionary History of Saber-Toothed Cats Based on Ancient Mitogenomics

Saber-toothed cats (Machairodontinae) are among the most widely recognized representatives of the now largely extinct Pleistocene megafauna. However, many aspects of their ecology, evolution, and extinction remain uncertain. Although ancient-DNA studies have led to huge advances in our knowledge of these aspects of many other megafauna species (e.g., mammoths and cave bears), relatively few ancient-DNA studies have focused on saber-toothed cats [1–3], and they have been restricted to short fragments of mitochondrial DNA. Here we investigate the evolutionary history of two lineages of saber-toothed cats (Smilodon and Homotherium) in relation to living carnivores and find that the Machairodontinae form a well-supported clade that is distinct from all living felids. We present partial mitochondrial genomes from one S. populator sample and three Homotherium sp. samples, including the only Late Pleistocene Homotherium sample from Eurasia [4]. We confirm the identification of the unique Late Pleistocene European fossil through ancient-DNA analyses, thus strengthening the evidence that Homotherium occurred in Europe over 200,000 years later than previously believed. This in turn forces a re-evaluation of its demography and extinction dynamics. Within the Machairodontinae, we find a deep divergence between Smilodon and Homotherium (∼18 million years) but limited diversity between the American and European Homotherium specimens. The genetic data support the hypothesis that all Late Pleistocene (or post-Villafrancian) Homotherium should be considered a single species, H. latidens, which was previously proposed based on morphological data [5, 6]. Paijmans et al. present ancient DNA from some of the most recognized extinct Pleistocene megafauna: the saber-toothed cats. The results elucidate the evolutionary history of these iconic carnivores and provide genetic evidence that saber-toothed cats existed in Europe over 200,000 years later than previously believed.This project received funding from the European Research Council (consolidator grant GeneFlow no. 310763 to M.H.), European Union’s Seventh Framework Programme for research, technological development, and demonstration (grant no. FP7-PEOPLE-2011-IEF-298820 to R.B.), and Lundbeck Foundation (grant no. R52-A5062 to M.L.Z.-M.)

Introduction: Examined Live – An Epistemological Exchange Between Philosophy and Cultural Psychology on Reflection

Besides the general agreement about the human capability of reflection, there is a large area of disagreement and debate about the nature and value of “reflective scrutiny” and the role of “second-order states” in everyday life. This problem has been discussed in a vast and heterogeneous literature about topics such as epistemic injustice, epistemic norms, agency, understanding, meta-cognition etc. However, there is not yet any extensive and interdisciplinary work, specifically focused on the topic of the epistemic value of reflection. This volume is one of the first attempts aimed at providing an innovative contribution, an exchange between philosophy, epistemology and psychology about the place and value of reflection in everyday life. Our goal in the next sections is not to offer an exhaustive overview of recent work on epistemic reflection, nor to mimic all of the contributions made by the chapters in this volume. We will try to highlight some topics that have motivated a new resumption of this field and, with that, drawing on chapters from this volume where relevant. Two elements defined the scope and content of this volume, on the one hand, the crucial contribution of Ernest Sosa, whose works provide original and thought-provoking contributions to contemporary epistemology in setting a new direction for old dilemmas about the nature and value of knowledge, giving a central place to reflection. On the other hand, the recent developments of cultural psychology, in the version of the “Aalborg approach”, reconsider the object and scope of psychological sciences, stressing that “[h]uman conduct is purposeful”

Suppression of intratumoral CCL22 by type I interferon inhibits migration of regulatory T cells and blocks cancer progression

The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to blunt Treg activity that can limit immune escape and promote tumor rejection. Activation of innate immunity with Toll-like receptor (TLR) or RIG-I-like receptor (RLR) ligands prevented accumulation of Treg in tumors by blocking their immigration. Mechanistic investigations indicated Treg blockade was a consequence of reduced intratumoral CCL22 levels caused by type I interferon. Notably, stable expression of CCL22 abrogated the antitumor effects of treatment with RLR or TLR ligands. Taken together, our findings argue that type I interferon blocks the Treg-attracting chemokine CCL22 and thus helps limit the recruitment of Treg to tumors, a finding with implications for cancer immunotherapy