Showing papers by "University of Turin published in 2009"

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy

Abstract: Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

Genome-wide association study identifies eight loci associated with blood pressure

Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular Injury

Abstract: Administration of mesenchymal stem cells (MSCs) improves the recovery from acute kidney injury (AKI). The mechanism may involve paracrine factors promoting proliferation of surviving intrinsic epithelial cells, but these factors remain unknown. In the current study, we found that microvesicles derived from human bone marrow MSCs stimulated proliferation in vitro and conferred resistance of tubular epithelial cells to apoptosis. The biologic action of microvesicles required their CD44- and beta1-integrin-dependent incorporation into tubular cells. In vivo, microvesicles accelerated the morphologic and functional recovery of glycerol-induced AKI in SCID mice by inducing proliferation of tubular cells. The effect of microvesicles on the recovery of AKI was similar to the effect of human MSCs. RNase abolished the aforementioned effects of microvesicles in vitro and in vivo, suggesting RNA-dependent biologic effects. Microarray analysis and quantitative real time PCR of microvesicle-RNA extracts indicate that microvesicles shuttle a specific subset of cellular mRNA, such as mRNAs associated with the mesenchymal phenotype and with control of transcription, proliferation, and immunoregulation. These results suggest that microvesicles derived from MSCs may activate a proliferative program in surviving tubular cells after injury via a horizontal transfer of mRNA.

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.

Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls We carried out replication in an independent sample with an effective sample size of up to 19,492 SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9) We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3) We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk

Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency

Abstract: Background We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. Methods We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. Results All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxificati...

PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies.

Abstract: The monoclonal antibodies (moAb) panitumumab and cetuximab target the epidermal growth factor receptor (EGFR) and have proven valuable for the treatment of metastatic colorectal cancer (mCRC).EGFR-mediated signaling involves two main intracellular cascades: on one side KRAS activates BRAF, which in turn triggers the mitogen-activated protein kinases.On the other, membrane localization of the lipid kinase PIK3CA counteracts PTEN and promotes AKT1 phosphorylation, thereby activating a parallel intracellular axis. Constitutive activation of KRAS bypasses the corresponding signaling cascade and, accordingly, patients with mCRC bearing KRAS mutations are clinically resistant to therapy with panitumumab or cetuximab.We hypothesized that mutations activating PIK3CA could also preclude responsiveness to EGFR-targeted moAbs through a similar mechanism. Here, we present the mutational analysis of PIK3CA and KRAS and evaluation of the PTEN protein status in a cohort of 110 patients with mCRC treated with anti-EGFR moAbs.We observed 15 (13.6%) PIK3CA and 32 (29.0%) KRAS mutations. PIK3CA mutations were significantly associated with clinical resistance to panitumumab or cetuximab; none of the mutated patients achieved objective response (P = 0.038). When only KRAS wild-type tumors were analyzed, the statistical correlation was stronger (P = 0.016). Patients with PIK3CA mutations displayed a worse clinical outcome also in terms of progression-free survival (P = 0.035). Our data indicate that PIK3CA mutations can independently hamper the therapeutic response to panitumumab or cetuximab in mCRC.When the molecular status of the PIK3CA/PTEN and KRAS pathways are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to EGFR moAbs can be identified. [Cancer Res 2009;69(5):1851–7]

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

Abstract: The serum immunoglobulin-free light chain (FLC) assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.

The Differential Efficacy of Pemetrexed According to NSCLC Histology: A Review of Two Phase III Studies

Abstract: Background. Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of pemetrexed according to histology in two large, phase III NSCLC trials. Methods. One study tested pemetrexed versus docetaxel in previously treated patients (n 571) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n 1,725)withadvancedNSCLC.Coxproportionalhazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (OS) and progression-free survival (PFS). For each histologic subgroup, the Kaplan–Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-adjusted between-arm hazard ratios (HRs). Results.Inbothstudies,treatmentarmswerewellbalanced for histology. THIs were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups.

Plants, mycorrhizal fungi, and bacteria: a network of interactions.

Abstract: This review focuses on interactions among plants, mycorrhizal fungi, and bacteria, testing the hypothesis whether mycorrhizas can be defined as tripartite associations. After summarizing the main biological features of mycorrhizas, we illustrate the different types of interaction occurring between mycorrhizal fungi and bacteria, from loosely associated microbes to endobacteria. We then discuss, in the context of nutritional strategies, the mechanisms that operate among members of the consortium and that often promote plant growth. Release of active molecules, including volatiles, and physical contact among the partners seem important for the establishment of the bacteria/mycorrhizal fungus/plant network. The potential involvement of quorum sensing and Type III secretion systems is discussed, even if the exact nature of the complex interspecies/interphylum interactions remains unclear.

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types.

Abstract: The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification.

Abstract: BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, and it was only in 2004 that the International Union Against Cancer (UICC) defined TNM criteria and published the first staging classification. However, to date, the prognostic value of the proposed classification has not been evaluated. METHODS: The German ACC Registry comprising 492 patients was searched for patients who were diagnosed between 1986 and 2007 with detailed information on primary diagnosis and a minimum follow-up of 6 months. Patients were assigned to UICC tumor stage, and disease-specific survival (DSS) was assessed. In addition, the contribution of potential risk factors for DSS was evaluated. RESULTS: In total, 416 patients with a mean follow-up of 36 months met the inclusion criteria (stage I, n = 23 patients; stage II, n = 176 patients; stage III, n = 67 patients; stage IV, n = 150 patients). Kaplan-Meier analysis revealed a stage-dependent DSS. However, DSS in patients with stage II ACC did not differ significantly from DSS in patients with stage III ACC (hazard ratio, 1.38; 95% confidence interval, 0.89-2.16). Furthermore, patients who had stage IV ACC without distant metastases had an improved DSS compared with patients who had metastatic disease (P = .004). An analysis of different potential risk factors for defining stage III ACC revealed important roles in DSS for tumor infiltration in surrounding tissue, venous tumor thrombus (VTT), and positive lymph nodes; whereas tumor invasion in adjacent organs carried a prognosis similar to that of infiltration in surrounding tissue only. CONCLUSIONS: The 2004 UICC staging classification for ACC has significant limitations. On the basis of the current analysis, a revised classification with superior prognostic accuracy is proposed (the European Network for the Study of Adrenal Tumors classification). In this system, stage III ACC is defined by the presence of positive lymph nodes, infiltration of surrounding tissue, or VTT; and stage IV ACC is restricted to patients with distant metastasis. Cancer 2009. © 2009 American Cancer Society.

Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

Abstract: BACKGROUND Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. METHODS PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. RESULTS Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. CONCLUSIONS VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics.

Abstract: The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomics

Sex, attachment, and the development of reproductive strategies.

Abstract: This target article presents an integrated evolutionary model of the development of attachment and human reproductive strategies. It is argued that sex differences in attachment emerge in middle childhood, have adaptive significance in both children and adults, and are part of sex-specific life history strategies. Early psychosocial stress and insecure attachment act as cues of environmental risk, and tend to switch development towards reproductive strategies favoring current reproduction and higher mating effort. However, due to sex differences in life history trade-offs between mating and parenting, insecure males tend to adopt avoidant strategies, whereas insecure females tend to adopt anxious/ambivalent strategies, which maximize investment from kin and mates. Females are expected to shift to avoidant patterns when environmental risk is more severe. Avoidant and ambivalent attachment patterns also have different adaptive values for boys and girls, in the context of same-sex competition in the peer group: in particular, the competitive and aggressive traits related to avoidant attachment can be favored as a status-seeking strategy for males. Finally, adrenarche is proposed as the endocrine mechanism underlying the reorganization of attachment in middle childhood, and the implications for the relationship between attachment and sexual development are explored. Sex differences in the development of attachment can be fruitfully integrated within the broader framework of adaptive plasticity in life history strategies, thus contributing to a coherent evolutionary theory of human development.

The Governance of University Knowledge Transfer: A Critical Review of the Literature

Abstract: Universities have long been involved in knowledge transfer activities. Yet the last 30 years have seen major changes in the governance of university–industry interactions. Knowledge transfer has become a strategic issue: as a source of funding for university research and (rightly or wrongly) as a policy tool for economic development. Universities vary enormously in the extent to which they promote and succeed in commercializing academic research. The identification of clear-cut models of governance for university–industry interactions and knowledge transfer processes is not straightforward. The purpose of this article is to critically discuss university knowledge transfer models and review the recent developments in the literature on research collaborations, intellectual property rights and spin-offs, those forms of knowledge transfer that are more formalized and have been institutionalized in recent years. The article also addresses the role played by university knowledge transfer organizations in promoting commercialization of research results.

Biodistribution of gadolinium-based contrast agents, including gadolinium deposition.

Abstract: The biodistribution of approved gadolinium (Gd) based contrast agents (GBCA) is reviewed. After intravenous injection GBCA distribute in the blood and the extracellular space and transiently through the excretory organs. Preclinical animal studies and the available clinical literature indicate that all these compounds are excreted intact. Elimination tends to be rapid and for the most part, complete. In renally insufficient patients the plasma elimination half-life increases substantially from hours to days depending on renal function. In patients with impaired renal function and nephrogenic systemic fibrosis (NSF), the agents gadodiamide, gadoversetamide, and gadopentetate dimeglumine have been shown to result in Gd deposition in the skin and internal organs. In these cases, it is likely that the Gd is no longer present as the GBCA, but this has still not been definitively shown. In preclinical models very small amounts of Gd are retained in the bone and liver, and the amount retained correlates with the kinetic and thermodynamic stability of the GBCA with respect to Gd release in vitro. The pattern of residual Gd deposition in NSF subjects may be different than that observed in preclinical rodent models. GBCA are designed to be used via intravenous administration. Altering the route of administration and/or the formulation of the GBCA can dramatically alter the biodistribution of the GBCA and can increase the likelihood of Gd deposition.

Thermodynamic Bethe ansatz for planar AdS/CFT: a proposal

Abstract: Moving from the mirror theory Bethe?Yang equations proposed by Arutyunov and Frolov, we derive the thermodynamic Bethe ansatz equations which should control the spectrum of the planar AdS5/CFT4 correspondence. The associated set of universal functional relations (Y-system) satisfied by the exponentials of the TBA pseudoenergies is deduced, confirming the structure inferred by Gromov, Kazakov and Vieira.

Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: A randomized trial

Abstract: Context Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) ( Objective To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates. Design, Setting, and Patients Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis. Intervention Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 × 10 9 colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates Main Outcome Measure First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid. Results Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P Conclusion Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates. Trial Registration isrctn.org Identifier: ISRCTN53107700

Acupuncture for migraine prophylaxis

Abstract: BACKGROUND: Acupuncture is often used for migraine prophylaxis but its effectiveness is still controversial. This review (along with a companion review on'Acupuncture for tension-type headache') represents an updated version of a Cochrane review originally published in Issue 1, 2001, of The Cochrane Library. OBJECTIVES: To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than'sham' (placebo) acupuncture; and c) as effective as other interventions in reducing headache frequency in patients with migraine. SEARCH STRATEGY: The Cochrane Pain, Palliative& Supportive Care Trials Register, CENTRAL, MEDLINE, EMBASE and the Cochrane Complementary Medicine Field Trials Register were searched to January 2008. SELECTION CRITERIA: We included randomized trials with a post-randomization observation period of at least 8 weeks that compared the clinical effects of an acupuncture intervention with a control (no prophylactic treatment or routine care only), a sham acupuncture intervention or another intervention in patients with migraine. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility; extracted information on patients, interventions, methods and results; and assessed risk of bias and quality of the acupuncture intervention. Outcomes extracted included response (outcome of primary interest), migraine attacks, migraine days, headache days and analgesic use. Pooled effect size estimates were calculated using a random-effects model. MAIN RESULTS: Twenty-two trials with 4419 participants (mean 201, median 42, range 27 to 1715) met the inclusion criteria. Sixtrials (including two large trials with 401 and 1715 patients) compared acupuncture to no prophylactic treatment or routine care only. After 3 to 4 months patients receiving acupuncture had higher response rates and fewer headaches. The only study with long-term follow up saw no evidence that effects dissipated up to 9 months after cessation of treatment. Fourteen trials compared a'true' acupuncture intervention with a variety of sham interventions. Pooled analyses did not show a statistically significant superiority for true acupuncture for any outcome in any of the time windows, but the results of single trials varied considerably. Four trials compared acupuncture to proven prophylactic drug treatment. Overall in these trials acupuncture was associated with slightly better outcomes and fewer adverse effects than prophylactic drug treatment. Two small low-quality trials comparing acupuncture with relaxation (alone or in combination with massage) could not be interpreted reliably. AUTHORS' CONCLUSIONS: In the previous version of this review, evidence in support of acupuncture for migraine prophylaxis was considered promising but insufficient. Now, with 12 additional trials, there is consistent evidence that acupuncture provides additional benefit to treatment of acute migraine attacks only or to routine care. There is no evidence for an effect of'true' acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance. Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered a treatment option for patients willing to undergo this treatment.

Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized WT1 Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study

Abstract: Purpose. Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteristics. It remains to be established whether relapse risk can be better predicted through assessment of minimal residual disease (MRD). One proposed marker is the Wilms tumor gene WT1, which is overexpressed in most patients with AML, thus providing a putative target for immunotherapy, although in the absence of a standardized assay, its utility for MRD monitoring remains controversial. Patients and Methods. Nine published and in-house real-time quantitative polymerase chain reaction WT1 assays were systematically evaluated within the European LeukemiaNet; the best-performing assay was applied to diagnostic AML samples (n = 620), follow-up samples from 129 patients treated with intensive combination chemotherapy, and 204 normal peripheral blood (PB) and bone marrow (BM) controls. Results. Considering relative levels of expression detected in normal PB and BM, WT1 was sufficiently overexpressed to discriminate ≥ 2-log reduction in transcripts in 46% and 13% of AML patients, according to the respective follow-up sample source. In this informative group, greater WT1 transcript reduction after induction predicted reduced relapse risk (hazard ratio, 0.54 per log reduction; 95% CI, 0.36 to 0.83; P = .004) that remained significant when adjusted for age, WBC count, and cytogenetics. Failure to reduce WT1 transcripts below the threshold limits defined in normal controls by the end of consolidation also predicted increased relapse risk (P = .004). Conclusion. Application of a standardized WT1 assay provides independent prognostic information in AML, lending support to incorporation of early assessment of MRD to develop more robust risk scores, to enhance risk stratification, and to identify patients who may benefit from allogeneic transplantation.

Evolution, nucleosynthesis, and yields of low-mass asymptotic giant branch stars at different metallicities

Abstract: The envelope of thermally pulsing asymptotic giant branch (TP-AGB) stars undergoing periodic third dredge-up (TDU) episodes is enriched in both light and heavy elements, the ashes of a complex internal nucleosynthesis involving p, α, and n captures over hundreds of stable and unstable isotopes. In this paper, new models of low-mass AGB stars (2 M ☉), with metallicity ranging between Z = 0.0138 (the solar one) and Z = 0.0001, are presented. Main features are (1) a full nuclear network (from H to Bi) coupled to the stellar evolution code, (2) a mass loss-period-luminosity relation, based on available data for long-period variables, and (3) molecular and atomic opacities for C- and/or N-enhanced mixtures, appropriate for the chemical modifications of the envelope caused by the TDU. For each model, a detailed description of the physical and chemical evolutions is presented; moreover, we present a uniform set of yields, comprehensive of all chemical species (from hydrogen to bismuth). The main nucleosynthesis site is the thin 13C pocket, which forms in the core-envelope transition region after each TDU episode. The formation of this 13C pocket is the principal by-product of the introduction of a new algorithm, which shapes the velocity profile of convective elements at the inner border of the convective envelope: both the physical grounds and the calibration of the algorithm are discussed in detail. We find that the pockets shrink (in mass) as the star climbs the AGB, so that the first pockets, the largest ones, leave the major imprint on the overall nucleosynthesis. Neutrons are released by the 13C(α, n)16O reaction during the interpulse phase in radiative conditions, when temperatures within the pockets attain T ~ 1.0 × 108 K, with typical densities of (106-107) neutrons cm–3. Exceptions are found, as in the case of the first pocket of the metal-rich models (Z = 0.0138, Z = 0.006 and Z = 0.003), where the 13C is only partially burned during the interpulse: the surviving part is ingested in the convective zone generated by the subsequent thermal pulse (TP) and then burned at T ~ 1.5 × 108 K, thus producing larger neutron densities (up to 1011 neutrons cm–3). An additional neutron exposure, caused by the 22Ne(α, n)25Mg during the TPs, is marginally activated at large Z, but becomes an important nucleosynthesis source at low Z, when most of the 22Ne is primary. The final surface compositions of the various models reflect the differences in the initial iron-seed content and in the physical structure of AGB stars belonging to different stellar populations. Thus, at large metallicities the nucleosynthesis of light s-elements (Sr, Y, Zr) is favored, whilst, decreasing the iron content, the overproduction of heavy s-elements (Ba, La, Ce, Nd, Sm) and lead becomes progressively more important. At low metallicities (Z = 0.0001) the main product is lead. The agreement with the observed [hs/ls] index observed in intrinsic C stars at different [Fe/H] is generally good. For the solar metallicity model, we found an interesting overproduction of some radioactive isotopes, like 60Fe, as a consequence of the anomalous first 13C pocket. Finally, light elements (C, F, Ne, and Na) are enhanced at any metallicity.

Factorization constraints for soft anomalous dimensions in QCD scattering amplitudes

Abstract: We study the factorization of soft and collinear singularities in dimensionally- regularized fixed-angle scattering amplitudes in massless gauge theories. Our factorization is based on replacing the hard massless partons by light-like Wilson lines, and defining gauge-invariant jet and soft functions in dimensional regularization. In this scheme the factorized amplitude admits a powerful symmetry: it is invariant under rescaling of indi- vidual Wilson-line velocities. This symmetry is broken by cusp singularities in both the soft and the eikonal jet functions. We show that the cancellation of these cusp anomalies in any multi-leg amplitude imposes all-order constraints on the kinematic dependence of the corresponding soft anomalous dimension, relating it to the cusp anomalous dimension. For amplitudes with two or three hard partons the solution is unique: the constraints fully determine the kinematic dependence of the soft function. For amplitudes with four or more hard partons we present a minimal solution where the soft anomalous dimension is a sum over colour dipoles, multiplied by the cusp anomalous dimension. In this case additional contributions to the soft anomalous dimension at three loops or beyond are not excluded, but they are constrained to be functions of conformal cross ratios of kinematic variables.