Measurement of the

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values. Stellar model calculations indicate a reduction around 20% of the s-process contribution to the Galactic cerium abundance and smaller sizeable differences for most of the heavier elements. No variations are found in the nucleosynthesis from massive stars.

74 Ge( n , γ ) cross section below 70 keV measured at n_TOF CERN.

Neutron capture reaction cross sections on 74 Ge are of importance to determine 74 Ge production during the astrophysical slow neutron capture process. We present new resonance data on 74 Ge( n , γ ) reactions below 70 keV neutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experiment.

Neutron Capture on the s-Process Branching Point

The neutron capture cross sections of several unstable nuclides acting as branching points in the s process are crucial for stellar nucleosynthesis studies. The unstable ^{171}Tm (t_{1/2}=1.92 yr) is part of the branching around mass A∼170 but its neutron capture cross section as a function of the neutron energy is not known to date. In this work, following the production for the first time of more than 5 mg of ^{171}Tm at the high-flux reactor Institut Laue-Langevin in France, a sample was produced at the Paul Scherrer Institute in Switzerland. Two complementary experiments were carried out at the neutron time-of-flight facility (n_TOF) at CERN in Switzerland and at the SARAF liquid lithium target facility at Soreq Nuclear Research Center in Israel by time of flight and activation, respectively. The result of the time-of-flight experiment consists of the first ever set of resonance parameters and the corresponding average resonance parameters, allowing us to make an estimation of the Maxwellian-averaged cross sections (MACS) by extrapolation. The activation measurement provides a direct and more precise measurement of the MACS at 30 keV: 384(40) mb, with which the estimation from the n_TOF data agree at the limit of 1 standard deviation. This value is 2.6 times lower than the JEFF-3.3 and ENDF/B-VIII evaluations, 25% lower than that of the Bao et al. compilation, and 1.6 times larger than the value recommended in the KADoNiS (v1) database, based on the only previous experiment. Our result affects the nucleosynthesis at the A∼170 branching, namely, the ^{171}Yb abundance increases in the material lost by asymptotic giant branch stars, providing a better match to the available pre-solar SiC grain measurements compared to the calculations based on the current JEFF-3.3 model-based evaluation.

Jejunal metastasis of Merkel cell carcinoma: case report.

Merkel cell carcinoma (MCC) of the skin is a rare but aggressive cutaneous neuroendocrine-derived malignancy that predominantly affects elderly white males. The presence of distant nodal metastases significantly impacts survival. Typical metastatic sites of MCC are liver, bone, brain and skin. Gastrointestinal metastases are uncommon and small bowel is the most common site followed by stomach. We report a case of symptomatic MCC jejunal metastasis.

Silicon detectors for monitoring neutron beams in n-TOF beamlines.

During 2014, the second experimental area (EAR2) was completed at the n-TOF neutron beam facility at CERN (n-TOF indicates neutron beam measurements by means of time of flight technique). The neutrons are produced via spallation, by means of a high-intensity 20 GeV pulsed proton beam impinging on a thick target. The resulting neutron beam covers the energy range from thermal to several GeV. In this paper, we describe two beam diagnostic devices, both exploiting silicon detectors coupled with neutron converter foils containing (6)Li. The first one is based on four silicon pads and allows monitoring of the neutron beam flux as a function of the neutron energy. The second one, in beam and based on position sensitive silicon detectors, is intended for the reconstruction of the beam profile, again as a function of the neutron energy. Several electronic setups have been explored in order to overcome the issues related to the gamma flash, namely, a huge pulse present at the start of each neutron bunch which may blind the detectors for some time. The two devices were characterized with radioactive sources and also tested at the n-TOF facility at CERN. The wide energy and intensity range they proved capable of sustaining made them attractive and suitable to be used in both EAR1 and EAR2 n-TOF experimental areas, where they became immediately operational.

A call to standardize preanalytic data elements for biospecimens.

CONTEXT: Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Clinical preanalytic variables are the focus of this study. OBJECTIVE: To define the essential preanalytic variables (data fields) that should be attached to every collected biospecimen and to provide a complete list of such variables, along with their relative importance, which can vary, depending on downstream use, institutional needs, and information technology capabilities. DESIGN: The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a Biorepository Working Group to develop a ranked list of the preanalytic variables for annotating biospecimens. Members of the working group were experts in anatomic, clinical, and molecular pathology; biobanking; medical informatics; and accreditation. Several members had experience with federal government programs, such as the National Cancer Institute's Biospecimens and Biorepository Branch and the National Cancer Institute's Community Cancer Center Program. Potential preanalytic variables were identified and ranked along with available supporting evidence, definitions, and potential negative effects if the variable was not attached to the biospecimen. Additional national and international stakeholders reviewed the draft manuscript. RESULTS: The ranked listing of 170 preanalytic variables produced can be used as a guide for site-specific implementation into patient care and/or research biorepository processes. Conclusions.-In our collective experience, it is often difficult to choose which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research. The provided ranked list should aid in the selection of preanalytic variables for a given biospecimen collection.

Efficacy and safety of a salvage regimen based on tipranavir, enfuvirtide and three nucleoside analogues in HIV1 infected patients with clinical progression: 96-week evaluation.

In recent years, novel antiretroviral drugs have become available for multi-experienced HIV-infected patients with limited options. We enrolled seven advanced HIV-patients, failing multiple previous HAART regimens, in virological failure on their current HAART regimen and showing recent clinical and immunological progression. All patients were prescribed a double-boosted tipranavir plus enfuvirtide based regimen, in addition to zidovudine, tenofovir and lamivudine for salvage therapy. To assess susceptibility to tipranavir, the tipranavir genotypic resistance score was calculated and two years later this was re-evaluated on an updated tipranavir genotypic score algorithm. At baseline, CD4 were 139/mcL (more or less 145), HIV-1 RNA was 822,700 cp/mL. All patients achieved HIV-1 RNA levels less than 400 cp/mL between 12 weeks and 24 weeks of observation; two reached less than 50 cp/mL during this period. At 48 weeks three patients had reached less than 50 cp/mL; three other patients had HIV RNA less than 200 cp/mL. At 72 and 96 weeks HIV viraemia was less than 50 cp/mL in six patients; CD4 T-cell counts 285/mcL (more o less 198). No AIDS-defining events were recorded. Adverse events did not need to stop or change HAART. Strong 3 NRTI backbone could help efficacy and durability, and frequent evaluations in complex patients can help to manage toxicity.

Upgraded diagnostic value of Gen-Probe PACE 2 assay for detection of Chlamydia trachomatis infection.

In this study, we evaluate the performance of a nucleic acid amplification assay, COBAS AMPLICOR (Roche Molecular systems) (PCR), compared to non-amplified DNA probe assay PACE2 (Gen-Probe Inc.) for the detection of C. trachomatis in a total of 2,916 samples (2,114 females and 802 males) consecutively collected in two different clinical pathology laboratories, over a period of three years. In the females, the endocervical swabs showed a similar range of detection when using the two different methods: out of 1,581 females processed with PACE 2, 1.4% (2005), 0.9% (2006), 0.5% (2007), resulted positive for C. trachomatis; out of 533 females processed with PCR, 1.3% (2005), 1.5% (2006) and 1.2% (2007), resulted positive. However, in the male subjects we found an increased positivity of Chlamydia detection on urethral swabs by using PACE 2: 4.8% (2005), 1.9% (2006) and 2.9% (2007), compared to urine specimen processed by PCR: 1% (2005), 1.4% (2006) and 0% (2007). Even if PCR should be considered a most promising tool for routine diagnosis of Chlamydia infection, Gen Probe allowed us to better identify Chlamydia trachomatis (in 4.8% of urethral swabs compared to urine) leading to a hypothesis that extracellular EB forms of Chlamydia could be absent in urine in persistent infectious.

Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis.

OBJECTIVES: To compare cervical concentrations of numerous cytokines/chemokines in women with bacterial vaginosis (BV) compared with the levels detected after BV resolution and determine if hormonal contraceptive use modulates the local inflammatory response to BV. METHODS: Cervical secretions from 81 women with BV at enrollment and normal flora at one-month follow-up were analysed for 10 different cytokines/chemokines using multiplexed fluorescent bead-based immunoassays. RESULTS: BV was associated with significantly higher concentrations of IL-1 beta, tumour necrosis factor (TNF), interferon-gamma, IL-2, IL-4, and IL-10 compared with the levels detected in the presence of normal vaginal flora. Analysis of results stratified by contraceptive practice demonstrated significantly lower levels of numerous cytokines among women with BV using hormonal contraceptives compared with those women with BV not using hormonal contraceptives. Hormonal contraceptive use was also associated with a statistically significant lesser change in TNF levels between the two study visits compared with the amount of change detected between visits among women who denied their use. CONCLUSIONS: Despite increases in the levels of both pro and anti-inflammatory cytokines in the lower genital tract of women with BV, the overall balance of these two types of molecules was maintained. The character of this local inflammatory response may help explain the typical absence of overt signs of inflammation among women with BV. In addition, hormonal contraceptive use was associated with significantly lower levels of the pro-inflammatory molecules TNF, interferon-gamma, and granulocyte macrophage colony-stimulating factor in women with BV, but did not significantly reduce the levels of IL-10, a key anti-inflammatory cytokine. These results suggest the possibility of an association between hormonal contraceptive use and altered genital tract immunity.

Dielectron production in 12C+12C collisions at 2A GeV with the HADES spectrometer.

The invariant-mass spectrum of e+e- pairs produced in 12C+12C collisions at an incident energy of 2 GeV per nucleon has been measured for the first time. The measured pair production probabilities span over 5 orders of magnitude from the pi(0)-Dalitz to the rho/omega invariant-mass region. Dalitz decays of pi(0) and eta account for all the yield up to 0.15 GeV/c(2), but for only about 50% above this mass. A comparison with model calculations shows that the excess pair yield is likely due to baryon-resonance and vector-meson decays. Transport calculations based on vacuum spectral functions fail, however, to describe the entire mass region.

Gynecomastia in patients with prostate cancer: update on treatment options.

Non-steroidal antiandrogen monotherapy offers potential quality of life benefits over other treatment modalities in patients with prostate cancer. Nevertheless, gynecomastia and breast pain still represent the most bothersome side effects during this treatment. In this update article, recent advances in the management options for gynecomastia/breast pain caused by hormonal manipulation are reviewed and critically analyzed.

[Contribution of intraoperative radiotherapy in the control of local recurrences of rectal cancer]. / L'apporto della radioterapia intraoperatoria nel controllo della recidiva locale del cancro del retto.

Local recurrence (LR) is a major problem following curative resection of rectal cancer. Intraoperative radiation therapy (IORT) is considered an ideal boost technique for increasing the dose of radiation therapy within a restricted area without introducing a significant toxicity. The aim of this study is to present the results of a multimodality treatment containing external beam irradiation, chemotherapy, surgical resection, and IORT delivered by a movable linear accelerator (NOVAC7, Hitesys SpA, Italia), employed in a "traditional" operating room.

Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids.

(+)-1(R)-Coclaurine (1) and (-)-1(S)-norcoclaurine (3), together with quercetin 3-O-beta-D-glucuronide (4), were isolated from the leaves of Nelumbo nucifera (Nymphaceae), and identified as anti-HIV principles. Compounds 1 and 3 demonstrated potent anti-HIV activity with EC50 values of 0.8 and <0.8 microg/mL, respectively, and therapeutic index (TI) values of >125 and >25, respectively. Compound 4 was less potent (EC50 2 microg/mL). In a structure-activity relationship study, other benzylisoquinoline, aporphine, and bisbenzylisoquinoline alkaloids, including liensinine (14), negferine (15), and isoliensinine (16), which were previously isolated from the leaves and embryo of Nelumbo nucifera, were evaluated for anti-HIV activity. Compounds 14-16 showed potent anti-HIV activities with EC50 values of <0.8 microg/mL and TI values of >9.9, >8.6, and >6.5, respectively. Nuciferine (12), an aporphine alkaloid, had an EC50 value of 0.8 microg/mL and TI of 36. In addition, synthetic coclaurine analogs were also evaluated. Compounds 1, 3, 12, and 14-16 can serve as new leads for further development of anti-AIDS agents.

Anti-AIDS agents. Part 61: Anti-HIV activity of new podophyllotoxin derivatives.

A series of novel podophyllotoxin derivatives containing structural modifications at C-4 (7-14), C-4' (16-17), and the methylenedioxy A-ring (23-28) was synthesized and tested for inhibition of HIV replication. Four of these compounds (25-28) were previously reported to show EC(50) values of <0.001 microg/mL and therapeutic index (TI) values >120. Three of the newly tested compounds (8, 12, and 20) showed good activity with EC(50) values of 0.012, <0.001, and 0.389 microg/mL and TI values of 19.1, >16, and 19.4, respectively. A comparison of the anti-HIV activity of these derivatives suggested that an opened A-ring with 6,7-dimethoxy substitution and a 4'-demethylated E ring enhanced anti-HIV activity.

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women.

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.

Anti-ENA antibodies in patients with chronic hepatitis C virus infection.

The aim of the study was to assess the prevalence of anti-extractable nuclear antigen (ENA) antibodies in patients with chronic HCV infection. We studied 69 consecutive patients with chronic hepatitis C, 59 control subjects with non-HCV liver diseases, and 22 control subjects with extrahepatic, non-immune-mediated, chronic diseases. Thirty-two (46.3%) of 69 patients with HCV infection had anti-ENA antibodies: 16 (23.1%) showed anti-SSA antibodies and 14 (20.2%) had anti-SSB antibodies. Four of the patients with HCV infection suffered from sicca syndrome and three of them had also anti ENA antibodies. The prevalence of anti-ENA antibodies was significantly higher in the anti-HCV subjects compared with both control groups. Twenty-six of 44 HCV-antibodies-positive females had anti-ENA antibodies, compared with 6 of 25 males, showing a sex related difference. In conclusion, our results outline a specific role of HCV infection in the induction of anti-ENA antibodies. Female sex seems a predisposing condition.

Periampullary tumors. Analysis of 319 consecutive cases submitted to preoperative endoscopic biliary drainage.

BACKGROUND: During the last 2 decades, endoscopic retrograde cholangiopancreatography (ERCP) has been widely used for the diagnosis of periampullary tumors and the preoperative or definitive treatment of jaundice. METHODS: We performed a retrospective analysis of 319 consecutive patients (184 men and 135 women with an average age of 66.5 years) who underwent ERCP for periampullary tumors between 1987 and 1999. RESULTS: Endoscopic internal biliary drainage was successful in 293 patients (92%), with some differences due to the origin of the tumor. There were five complications (1.5%), including four bleeds and one retroduodenal perforation. There were no deaths related to the endoscopic drainage. Eighty-four patients underwent pancreaticoduodenectomy. The postoperative morbidity rate was 23%, and the overall mortality rate was 4.8%. CONCLUSION: ERCP is a valid technique for the detailed preoperative assessment of periampullary tumors. It is also a safe method for internal biliary drainage.

Selective use of endoscopic retrograde cholangiopancreatography to facilitate laparoscopic cholecystectomy without cholangiography. A review of 1139 consecutive cases.

BACKGROUND: The aim of this study was to show that laparoscopic cholecystectomy can be performed safely without routine intraoperative cholangiography. METHODS: We performed a retrospective analysis of 1139 consecutive patients (376 men and 763 women with an average age of 51.4 years) who underwent laparoscopic cholecystectomy between 1991 and 1999. In all, 227 patients (20%) were selected to undergo preoperative endoscopic retrograde cholangiopancreatography (ERCP) on the basis of four criteria for risk of stones. RESULTS: ERCP allowed us to make a diagnosis of biliary stones in 53.3% of the selected patients. Extraction of the stones was successful in 97% of the cases. In 14% of cases, ERCP was normal; in 32.7%, some useful diagnostic information was obtained. There were three complications (pancreatitis) following endoscopy (complication rate, 1.3%). Laparoscopic cholecystectomy was successful in 92% of patients. The postoperative morbidity rate was 3.2% (major complications, 0.5%). There were no deaths. During a follow-up period ranging from 3 to 97 months, six patients (0.6%) were found to have residual biliary stones. CONCLUSION: This study confirms the hypothesis that laparoscopic cholecystectomy can be performed safely without routine intraoperative cholangiography.