Contribution to the geology of Southern Turkey: new insights from the Mersin mélanges and from the Lycian and Antalya nappes

Abstract The study of fossil Tethyan continental margins implies the consideration of the oceanic domains to which they were connected. The advent of plate tectonics confirmed the importance of the detection of accretion-related mélanges. Ophiolitic mélanges are derived from both an upper ophiolitic obducting plate and a lower oceanic plate. Besides ophiolitic elements, the mélanges may incorporate parts of a magmatic arc and dismembered fragments of a passive continental margin. As the lower plate usually totally disappears during the obduction process, it can only be reconstructed from its elements found in the mélanges. Because of their key location at active margin boundaries, preserved accretion-related mélanges provide strong constraints on the geological evolution of former oceanic domains and their adjacent margins. The identification of Palaeotethyan remnants as accretionary series or reworked during the Late Triassic Eo-Cimmerian event, as well as the recognition of HugluPindos marginal sequences in southern Turkey and in the external Hellenides represent the main achievements of this work, making possible to establish new palaeogeographical correlations. The Mersin mélanges (Turkey), together with the Antalya and Mamonia (Cyprus) domains, are characterized by a series of exotic units found now south of the main Taurus range and compose the South-Taurides Exotic Units. The Mersin mélanges are subdivided in a Triassic and a Late Cretaceous unit. These units consist of the remnants of three major Tethyan oceans, the Palaeotethys, the Neotethys and the Huglu-Pindos. The definition and inventory of the Upper Antalya Nappes (Turkey) are still a matter of controversies and often conflicting interpretations. The recognition of Campanian radiolarians on top of the Kerner Gorge unit directly overlain by the Ordovician Seydi§ehir Fm. of the Tahtah Dag Nappe outlines a tectonic contact and demonstrates that the Upper Antalya Nappes system is composed of three different nappes, the Kerner Gorge, Bakirli and the Tahtah Dag nappes. Additionally, a limestone block in a doubtful tectonic position at the base of the Upper Antalya Nappes yielded for the first time two middle Viséan associations of foraminifers and problematic algae. The Tavas Nappe in the Lycian Nappes (Turkey) is classically divided into the Karadag, Teke Dere, Köycegiz and Haticeana units. As for the Mersin mélanges, the Tavas Nappe is highly composite and includes dismembered units belonging to the Palaeotethyan, Neotethyan and HugluPindos realms. The Karadag unit consists of a Gondwana-type platform succession ranging from the Late Devonian to the Late Triassic. It belongs to the Cimmerian Taurus terrane and was part of the northern passive margin of the Neotethys. The Teke Dere unit is composed of different parts of the Palaeotethyan succession including Late Carboniferous OIB-type basalts, Carboniferous MORB-type basalts, an Early Carboniferous siliciclastic series and a Middle Permian arc sequence. The microfauna and microflora identified in different horizons within the Teke Dere unit share strong biogeographical affinities with the northern Palaeotethyan borders. Kubergandian limestones in primary contact above the Early Carboniferous siliciclastics yielded a rich and diverse microfauna and microflora also identified in reworked cobbles within the Late Triassic Gevne Fm. of the Aladag unit (Turkey). The sedimentological evolution of the Köycegiz and Haticeana series is in many points similar to classical Pindos sequences. These series originated in the Huglu-Pindos Ocean along the northern passive margin of the Anatolian (Turkish transect) and Sitia-Pindos (Greek transect) terranes. Conglomerates at the base of the Lentas Unit in southern Crete (Greece) yielded a microfauna and microflora presenting also strong affinities with the northern borders of the Palaeotethys. This type of reworked sediments at the base of Pindos-like series would suggest a derivation from the Palaeotethyan active margin. -Résumé (French abstract) L'étude des marges continentales fossiles de l'espace téthysien implique d'étudier les domaines océaniques qui y étaient rattachés. Les progrès de la tectonique des plaques ont confirmé l'importance de la reconnaissance des mélanges d'accrétion. Les mélanges ophiolitiques dérivent d'une plaque supérieure ophiolitique qui obducte, et d'une plaque inférieure océanique. En plus d'éléments ophiolitiques, les mélanges peuvent aussi incorporer des parties d'un arc magmatique, ou des fragments d'une marge continentale passive. Comme la plaque inférieure disparaît généralement complètement durant le processus d'obduction, elle ne peut être reconstruite qu'au travers de ses éléments trouvés dans les mélanges. A cause de leur situation aux limites de marges actives, les mélanges d'accrétion bien préservés permettent de contraindre l'évolution géologique d'anciens océans et de leurs marges. L'identification de vestiges de la Paléotéthys en série d'accrétion ou remaniés lors de l'orogenèse éo-cimmérienne au Trias supérieur, ainsi que l'observation de séquences marginales de Huglu-Pinde en Turquie du sud et dans les Hellénides externes représentent les principaux résultats de ce travail, permettant d'établir de nouvelles corrélations paléogéographiques. Les mélanges de Mersin (Turquie), avec les domaines d'Antalya et de Mamonia (Chypre), sont caractérisés par des unités exotiques se trouvant au sud de la chaîne taurique, et forment les Unités Exotiques Sud-Tauriques. Les mélanges de Mersin sont subdivisés en une unité triasique, et une autre du Crétacé supérieur. Ces unités comprennent les reliques de trois principaux océans téthysiens, la Paléotéthys, la Néotéthys et Huglu-Pinde. L'inventaire et la définition des nappes supérieures d'Antalya (Turquie) sont encore matière à controverse et donne lieu à des interprétations conflictuelles. La découverte de radiolaires campaniens au sommet de l'unité de la Gorge de Kemer, directement recouverts par la formation ordovicienne de Seydisehir de la nappe du Tahtali Dag met en évidence un contact tectonique et démontre que les nappes supérieures sont composées de trois différentes nappes, celle de la Gorge de Kemer, celle du Bakirli et celle Tahtali Dag. De plus, un bloc de calcaire dont la position tectonique demeure incertaine à la base des nappes supérieures a fourni pour la première fois deux associations viséennes de foraminifères et d'algues problématiques. La nappe de Tavas dans les nappes lyciennes (Turquie) est séparée en unités du Karadag, du Teke Dere, de Köycegiz et d'Haticeana. Comme pour les mélanges de Mersin, la nappe de Tavas est composite et inclut des unités appartenant à la Paléotéthys, à la Néotéthys et à Huglu-Pinde. L'unité du Karadag est une plateforme carbonatée de type Gondwana se développant du Dévonien supérieur au Trias supérieur. Elle appartient au domaine cimmérien du Taurus et formait la marge nord de la Néotéthys. L'unité du Teke Dere est composée de différentes écailles paléotéthysiennes et inclut des basaltes d'île océanique du Carbonifère supérieur, des basaltes de ride océanique du Carbonifère, une série siliciclastique du Carbonifère supérieur et un arc du Permien moyen. Les microfaunes et -flores trouvées à différents niveaux de la série du Teke Dere partagent de fortes affinités paléogéographiques avec les marges nord de la Paléotéthys. Des calcaires du Kubergandien en contact primaire au-dessus de la série siliciclastique a donné de riches microfaunes et -flores, également identifiées dans des galets remaniés dans la formation de Gevne du Trias supérieur de l'Aladag. L'évolution sédimentologique des séries de Köycegiz et d'Haticeana sont très similaires aux séries classiques du Pinde. Ces séquences prennent leur racine dans l'océan de Huglu-Pinde, le long de la marge passive nord anatolienne (profil turc) et de la marge de Sitia-Pinde (profil grec). Des conglomérats à la base de l'unité de Lentas au sud de la Crète (Grèce) ont donné des microfaunes et flores partageant également de fortes similitudes avec les bordures nord de la Paléotéthys. Le type de sédiments remaniés à la base d'unités de type Pinde suggère une dérivation depuis la marge active de la Paléotéthys. -Résumé grand public (non-specialized abstract) Au début du 20ème siècle, Alfred Wegener bouleverse les croyances géologiques de l'époque et publie plusieurs articles sur la dérive ou la translation des continents. En utilisant des arguments géographiques (similarités des lignes de côte), paléontologiques (faunes et flores similaires) et climatiques (dépôts tropicaux et glaciaires), Wegener explique qu'il y a plusieurs millions d'années, les terres émergées actuelles ne devaient former qu'un seul et grand continent. La fin du 20ème siècle verra l'avènement de la théorie de la tectonique des plaques suite à la reconnaissance du cycle de Wilson, des rides médio-océaniques, des anomalies magnétiques dans les océans et des sutures océaniques qui représentent les reliques d'océans disparus. Le Cycle de Wilson se caractérise par une suite d'évènements géologiques majeurs pouvant se résumer de la manière suivante : (1) séparation d'un craton continental en deux parties, créant une limite de plaque divergente. C'est ce que l'on appelle un rift; (2) développement et croissance d'un océan entre ces deux blocs. Des roches magmatiques remontent à la surface de la terre et forment une chaîne de montagne sous-marine que l'on appelle ride médio-océanique ou dorsale. L'océan continue de se développer, et des sédiments se déposent à sa surface formant la suite ophiolitique ou trinité de Steinmann; (3) après une phase d'expansion plus ou moins longue, les conditions imposées aux limites des plaques à la surface de la terre changent, et l'océan se met à se refermer par disparition progressive (subduction) de sa croûte océanique sous une croûte continentale par exemple. Ceci crée une nouvelle limite de plaque, convergente cette fois; (4) la subduction de la plaque océanique sous la plaque continentale provoque une remontée de magma formant des chaînes volcaniques à la surface de la Terre ; (5) une fois que la plaque océanique a complètement disparu, les deux blocs préalablement séparés par l'océan font collision, formant ainsi une chaîne de montagne. Les chaînes de montagnes sont de manière générale formées par un empilement plus ou moins complexe de nappes. C'est au coeur de certaines de ces nappes que se trouvent les vestiges de l'océan disparu. Un des objectifs de ce travail était la recherche de ces vestiges dans le domaine téthysien de la Méditerranée orientale. Pour ce faire, nous avons parcourus une grande partie du sud de la Turquie, nous sommes allés à Chypre, dans le Sultanat d'Oman, en Iran, en Crète, et nous avons visités quelques îles grecques du Dodécanèse. La région de la Méditerranée orientale est une zone qui a été tectoniquement très active, et qui continue de l'être de nos jours par des phénomènes de subduction (ex. les volcans de Santorin), et par des mouvements coulissants entre des plaques continentales (ex. la faille nord-anatolienne) qui donnent régulièrement lieu à des tremblements de terre. Pour le géologue, la complexité de ces zones d'étude réside dans le fait que les chaînes de montagne actuelles ne contiennent en général pas seulement les restes d'un océan, mais bien de plusieurs bassins océaniques qui se sont succédés dans l'espace et dans le temps. Les nappes qui se trouvent au sud de la Turquie et dans le Dodécanèse forment un important jalon dans la chaîne alpine qui s'étend depuis les Alpes jusque dans l'Himalaya. L'idée d'un continuum au coeur de ce système se basait principalement sur l'âge des océans et sur la reconnaissance de similarités dans l'évolution des séries sédimentaires. La localisation des vestiges de la Paléotéthys ainsi que l'identification des séries sédimentaires ayant appartenu à l'océan de HugluPinde repris sous forme de nappes en Turquie et en Grèce sont cruciales pour permettre de bonnes corrélations locales et régionales. La reconnaissance, la compréhension et l'interprétation de ces séries sédimentaires permettront d'élaborer un modèle d'évolution géodynamique régional, s'appuyant sur des faits de terrains indiscutables, et prenant en compte les contraintes globales que ce genre d'exercice implique.

Long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced HIV-infected children.

AIM: To evaluate the long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/ritonavir in antiretroviral-experienced, initially protease inhibitor (PI)-naive, human immunodeficiency virus (HIV)-1-infected children. METHODS: HIV-1-infected children enrolled in the Swiss Mother and Child HIV Cohort Study were eligible for this observational cohort study if they received at least 1 PI of interest between March 1996 and October 2003: ritonavir, nelfinavir, or lopinavir/ritonavir. Data regarding demographics, clinical disease and antiretroviral treatment history, HIV-1 RNA copies/mL, CD4 T-cell counts [absolute (cells/microL) and percentages (%)], adverse events, clinical laboratory values, reasons for discontinuation of PIs, and concomitant medications were extracted from the database for PI-naive (first-line) and PI-experienced (second- or higher-line) PI use. RESULTS: The total duration of ritonavir, nelfinavir, and lopinavir/ritonavir use for 133 HIV-1-infected children was 163.8, 235.0, and 46.1 patient-years, respectively. In an on-treatment analysis, first-line therapy with any of the PIs significantly reduced HIV-1 concentrations and increased CD4 T-cell counts and percentages from baseline throughout the 288-week study (P <or= 0.05) for ritonavir and nelfinavir and throughout 84 weeks of use for lopinavir/ritonavir, which was introduced into treatment more recently. All PIs investigated were most effective in PI-naive children. Thirteen PI-associated toxicities occurred requiring treatment changes or interruptions (neurologic symptoms, n = 2; pancreatitis, n = 1; allergic reactions, n = 4; visual symptoms, n = 3; and hyperlipidemia, n = 3). CONCLUSIONS: Long-term PI-based therapy seems to be safe and to result in durable virologic and immunologic effectiveness in HIV-1-infected antiretroviral-experienced children.

Requiem pour la schizoïdie ?

La notion de schizoïdie, élaborée il y a une centaine d'années, est agonisante. On en retrace ici brièvement l'histoire, et montre comment certaines des discussions qu'elle a suscitées dans la première moitié du xxe siècle anticipaient plusieurs des débats actuels autour de la schizophrénie. Et si le terme lui-même peut bien disparaître, la conception qu'en avait E. Minkowski, mettant l'accent sur les distorsions de la présence au monde du sujet, devrait contribuer à enrichir notre compréhension de la psychopathologie, trop imprégnée aujourd'hui d'une perspective objectiviste.

Composition of weight gain during the neonatal period and longitudinal growth follow-up in premature babies.

Changes in the rate of growth and adiposity index (Quetelet index), calculated as weight/(length)2, kg/m2, were monitored from birth to 3 years in 19 premature babies (post-conceptional age 31.2 +/- 2 weeks) who were subjected during rapid growth (16 +/- 4 g/kg.day) to initial metabolic balance studies in the first weeks of life. These studies showed that the rate of fat accretion in these infants (3.3 +/- 0.9 g/kg.day) was substantially greater than that observed in fetuses of the same gestational age (2 g/kg.day) but the adiposity index was lower (9.6 +/- 1 kg/m2) than intrauterine values (11 kg/m2). Since at 6 months of age (corrected for gestational age at birth) the adiposity index was close to normality (103% of standard), the greater rate of fat accretion in early life contributed to progressively restore total body fat in premature babies. It is concluded that despite substantial fat deposition during the first weeks of life, the future evolution of these premature babies is favourable as judged from the normalization of adiposity index within the first 2 years of life.

Intermittent hemodialysis treatment in cefepime-induced neurotoxicity: Case report, pharmacokinetic modeling, and review of the literature.

Cefepime is a broad-spectrum cephalosporin indicated for in-hospital treatment of severe infections. Acute neurotoxicity, an increasingly recognized adverse effect of this drug in an overdose, predominantly affects patients with reduced renal function. Although dialytic approaches have been advocated to treat this condition, their role in this indication remains unclear. We report the case of an 88-year-old female patient with impaired renal function who developed life-threatening neurologic symptoms during cefepime therapy. She was treated with two intermittent 3-hour high-flux, high-efficiency hemodialysis sessions. Serial pre-, post-, and peridialytic (pre- and postfilter) serum cefepime concentrations were measured. Pharmacokinetic modeling showed that this dialytic strategy allowed for serum cefepime concentrations to return to the estimated nontoxic range 15 hours earlier than would have been the case without an intervention. The patient made a full clinical recovery over the next 48 hours. We conclude that at least 1 session of intermittent hemodialysis may shorten the time to return to the nontoxic range in severe clinically patent intoxication. It should be considered early in its clinical course pending chemical confirmation, even in frail elderly patients. Careful dosage adjustment and a high index of suspicion are essential in this population.

Prise en charge des endométriomes et de l'endométriose recto-vaginate et vésicate [Management of endometrioma, recto-vaginal and bladder endometriosis].

Endometriosis is a frequent, benign, chronic disease associated with pain and/or infertility. Classically the lesions are found on the pelvic peritoneum, ovary (endometrioma), rectovaginal septum and bladder. Management of endometrioma has evolved over the last few years to individualised treatment. Indeed endometrioma cystectomy can decrease pain and the risk of recurrence but is also associated with a decrease in ovarian reserve. A multi-disciplinary team should manage recto-vaginal or bladder endometriosis. Surgical resection of these lesions must be as complete as possible and can be complex.

Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.

Plasma liver-enzyme tests are widely used in the clinic for the diagnosis of liver diseases and for monitoring the response to drug treatment. There is considerable evidence that human genetic variation influences plasma levels of liver enzymes. However, such genetic variation has not been systematically assessed. In the present study, we performed a genome-wide association study of plasma liver-enzyme levels in three populations (total n = 7715) with replication in three additional cohorts (total n = 4704). We identified two loci influencing plasma levels of alanine-aminotransferase (ALT) (CPN1-ERLIN1-CHUK on chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), and three loci for alkaline phosphatase (ALP) levels (ALPL on chromosome 1, GPLD1 on chromosome 6, and JMJD1C-REEP3 on chromosome 10). In addition, we confirmed the associations between the GGT1 locus and GGT levels and between the ABO locus and ALP levels. None of the ALP-associated SNPs were associated with other liver tests, suggesting intestine and/or bone specificity. The mechanisms underlying the associations may involve cis- or trans-transcriptional effects (some of the identified variants were associated with mRNA transcription in human liver or lymphoblastoid cells), dysfunction of the encoded proteins (caused by missense variations at the functional domains), or other unknown pathways. These findings may help in the interpretation of liver-enzyme tests and provide candidate genes for liver diseases of viral, metabolic, autoimmune, or toxic origin. The specific associations with ALP levels may point to genes for bone or intestinal diseases.

The work of Spanish men. A quantitative analysis based on census data, 1900-1970

This paper presents a historical examination of employment in old age in Spain, in order to characterize this labour segment and identify and analyse its specific problems. One of these problems is the life-cycle deskilling process, already shown for certain national cases. This study explores whether this hypothesis also holds in Spain. The perspective used is essentially quantitative, as our analysis is based on the age-profession tables in Spanish population censuses from 1900 to 1970.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. METHODS: In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. FINDINGS: Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8-28·8) in the cilengitide group and 26·3 months (23·9-34·7) in the control group (hazard ratio 1·02, 95% CI 0·81-1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). INTERPRETATION: The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. FUNDING: Merck KGaA, Darmstadt, Germany.

Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.

Similar to human chronic lymphocytic leukemia (CLL), the de novo New Zealand Black (NZB) mouse model has a genetically determined age-associated increase in malignant B-1 clones and decreased expression of microRNAs miR-15a and miR-16 in B-1 cells. In the present study, lentiviral vectors were employed in vivo to restore miR-15a/16, and both the short-term single injection and long-term multiple injection effects of this delivery were observed in NZB. Control lentivirus without the mir-15a/16 sequence was used for comparison. We found that in vivo lentiviral delivery of mir-15a/16 increased miR-15a/16 expression in cells that were transduced (detected by GFP expression) and in sera when compared with control lentivirus treatment. More importantly, mice treated with the miR-expressing lentivirus had decreased disease. The lentivirus had little systemic toxicity while preferentially targeting B-1 cells. Short-term effects on B-1 cells were direct effects, and only malignant B-1 cells transduced with miR-15a/16 lentivirus had decreased viability. In contrast, long-term studies suggested both direct and indirect effects resulting from miR-15a/16 lentivirus treatment. A decrease in B-1 cells was found in both the transduced and non-transduced populations. Our data support the potential use of systemic lentiviral delivery of miR-15a/16 to ameliorate disease manifestations of CLL.

A natural structural variant of the mouse TCR beta-chain displays intrinsic receptor function and antigen specificity.

The Cbeta0 alternate cassette exon is located between the Jbeta1 and Cbeta1 genes in the mouse TCR beta-locus. In T cells with a VDJbeta1 rearrangement, the Cbeta0 exon may be included in TCRbeta transcripts (herein called TCRbeta-Cbeta0 transcripts), potentially inserting an additional 24 aa between the V and C domains of the TCR beta-chain. These TCRbeta splice isoforms may be differentially regulated after Ag activation, because we detected TCRbeta-Cbeta0 transcripts in a high proportion (>60%) of immature and mature T cells having VDJbeta1 rearrangements but found a substantially reduced frequency (<35%) of TCRbeta-Cbeta0 expression among CD8 T cells selected by Ag in vivo. To study the potential activity of the TCRbeta-Cbeta0 splice variant, we cloned full-length TCR cDNAs by single-cell RT-PCR into retroviral expression vectors. We found that the TCRbeta-Cbeta0 splice isoform can function during an early stage of T cell development normally dependent on TCR beta-chain expression. We also demonstrate that T hybridoma-derived cells expressing a TCRbeta-Cbeta0 isoform together with the clonally associated TCR alpha-chain recognize the same cognate peptide-MHC ligand as the corresponding normal alphabetaTCR. This maintenance of receptor function and specificity upon insertion of the Cbeta0 peptide cassette signifies a remarkable adaptability for the TCR beta-chain, and our findings open the possibility that this splice isoform may function in vivo.

Centre de la prostate: une approche multidisciplinaire pour une prise en charge globale du patient [Prostate cancer center: a multidisciplinary approach to accurately manage patients with prostate cancer]

The prostate cancer is a complex pathology involving oncological, functional and psychosocial items. The prostate's center of CHUV harmonize the know-how of urologists, oncologist, radiotherapists and clinical nurses to offer a global management to patients attempts by prostate cancer, from diagnosis to therapy and follow-up.