NETTAB 2012 on “Integrated Bio-Search”

The NETTAB 2012 workshop, held in Como on November 14-16, 2012, was devoted to "Integrated Bio-Search", that is to technologies, methods, architectures, systems and applications for searching, retrieving, integrating and analyzing data, information, and knowledge with the aim of answering complex bio-medical-molecular questions, i.e. some of the most challenging issues in bioinformatics today. It brought together about 80 researchers working in the field of Bioinformatics, Computational Biology, Biology, Computer Science and Engineering. More than 50 scientific contributions, including keynote and tutorial talks, oral communications, posters and software demonstrations, were presented at the workshop. This preface provides a brief overview of the workshop and shortly introduces the peer-reviewed manuscripts that were accepted for publication in this Supplement

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study

ObjectiveHypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis.Research design and methodsConsecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy.ResultsA total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT.ConclusionTestosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life

Towards a map of the Upper Pleistocene loess of the Po Plain Loess Basin (Northern Italy)

Upper Pleistocene (MIS 4-2) loess sequences occur in most of continental Europe and in Northern Italy along the Po Plain Loess Basin. Loess is distributed along the flanks of the Po Plain and was deposited on glacial deposits, fluvial terraces, uplifted isolated hills, karst plateaus, slopes and basins of secondary valleys. Loess bodies are generally tiny and affected by pedogenesis, being locally slightly reworked by slope processes and bioturbation. Notwithstanding, loess in the Po Plain is an important archive of paleoenviron-mental record and its mapping provides new insights in paleoenvironmental and palaeoseismic reconstructions of Northern Ital

Rapid biolayer interferometry measurements of urinary CXCL9 to detect cellular infiltrates noninvasively after kidney transplantation

Introduction: measuring the chemokine CXCL9 in urine by enzyme-linked immunosorbent assay (ELISA) can diagnose acute cellular rejection (ACR) noninvasively after kidney transplantation, but the required 12- to 24-hour turnaround time is not ideal for rapid, clinical decision-making. Methods: we developed a biolayer interferometry (BLI)−based assay to rapidly measure urinary CXCL9 in 200 pg/ml in subjects with ACR and ≤100 pg/ml in subjects with stable kidney function without cellular infiltrates. In samples obtained after treatment for ACR, BLI CXCL9 measurements detected biopsy-proven intragraft infiltrates despite treatment-induced reduction in serum creatinine. Discussion: together, our proof-of-principle results demonstrate that BLI-based urinary CXCL9 detection has potential as a point-of-care noninvasive biomarker to diagnose and guide therapy for ACR in kidney transplantation recipients

Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10-8 and 6.4 × 10-4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories

Accumulation of copy number alterations and clinical progression across advanced prostate cancer

Background: Genomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown. Methods: We performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression. Results: The burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10−6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov–Smirnov distance, 0.5; adjusted P<0.0001). Copy number alterations showed variability across tumour regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037). Conclusions: Copy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes

The beginning of the Neolithic in the Po Plain (northern Italy): Problems and perspectives

The Po Valley is one of the major physiographic units of northern Italy. It can be considered as a key area for the interpretation of long-term historical events and processes because of its location midway between the Mediterranean world and continental Europe. This paper is an updated summary of our knowledge of the Early Neolithic farming communities of the region. In particular it discusses data derived from radiocarbon dated sites. Its aim is to provide the international audience with an updated view of the topic, based on the discussion of a new series of AMS radiocarbon results, to frame the earliest producing communities of the Po Valley into the more general picture of the Neolithization of Italy. To achieve the goal, apart from radiocarbon assays, we have taken into consideration material culture remains, subsistence economy, environmental resources, and data gathered from archaeometric analyses and technology

Risultati preliminari delle indagini archeologiche ed etnografiche presso il sito di Togolok 1

Modern Turkmenistan is mainly constituted by a desert landscape, yet despite its harsh climate, cultures have been able to construct networks of water channels since the Bronze Age. This has resulted in a man-made landscape that integrates towns and villages. Extensive surveys and recent archaeological excavations have highlighted that between 2400 and 2100 BC (Namazga V period), the region of the Murghab alluvial fan was characterised by the development of complex urban societies. However, starting from the Late Bronze Age, a new group of mobile pastoralists appeared in the Murghab region and settled along the edges of the sedentary sites. Although their presence is well-attested both by survey and excavation data, their degree of interaction with the sedentary farmers is still debated. In modern Turkmenistan, semi-mobile shepherds continue to drive their cattle across the Murghab, using mobile camps for different months. This paper presents the preliminary results of the excavation of the sedentary site of Togolok 1, as well as the first ethnographic study of the mobile communities of the Murghab region

Reggio in età romana ed i suoi corsi d'acqua: un approccio geoarcheologico

La città di Reggio Emilia sors su un conoide originato dal torrente Crostolo. Questa indagine geoarcheologica dimostra però che la situazione relativa all'idrografia era molto complessa in età romana e vedeva la compresenza di differenti corsi d'acqua che hanno fortemente condizionato il disegno urbano e lo sviluppo di Regium Lepidi