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Categorically bounded free recall allows generating perceptual and cognitive contents within specific categories while avoiding unrelated intrusions. Previous research suggested that this is implemented via amplification of ultra-slow spontaneous activity fluctuations, initiating a spontaneous recall event. However, the underlying amplification mechanism remains unclear. Here, we demonstrate, using a simulation of a simple random recurrent neuronal network operating near a critical point, that such selective amplification can be generated by a small shift towards this critical point, resulting in a dynamical phenomenon termed “critical slowing down”. By fitting physiological parameters and applying stochastic white noise input, we simulated ultra-slow fluctuations observed during rest and categorically bounded visual recall in the human cortex. Our findings suggest that modulation of spontaneous fluctuations linked to free recall can be explained by a stochastically driven recurrent network near a critical point, providing insight into the rapid and flexible formation of categorical boundaries in human cognition.

The rapid adoption of marriage equality legislation for non-heterosexual individuals in Europe is attributed to many factors, including dramatic shifts in public opinion, the work of transnational activists and changing international norms. Usually, these factors must be filtered through the halls of parliaments where most policy change happens. Given the importance of parliamentarians’ attitudes, it is surprising that we know so little about how attitudes towards same-sex marriage are distributed across political candidates in Europe and what factors shape them. This article fills that gap by using an underutilised dataset on the political preferences of candidates for parliamentary office. We find that beyond attachment to party families, a candidate’s religiosity and practice has a greater effect on a would-be Member of Parliament’s attitudes towards same-sex marriage. The findings suggest that the success of parliamentary action on lesbian, gay, bisexual and transgender rights depends not on the partisan composition of the legislature, but rather on the representation of secular candidates.

Despite a growing population of students being served in Alternative Education Settings (AES) and a severe teacher shortage in AES, most traditional teacher preparation programs do not specifically...

Understanding diversity in the genus Xerocomellus in western North America has been obscured by morphological variability, widespread use of species epithets typified by specimens from Europe and eastern North America, misunderstood phylogenetic relationships, and species complexes. We collected extensively and used genetic and morphological data to establish the occurrence of ten Xerocomellus species in western North America. We generated ITS sequences from five type collections and from vouchered representative collections to clarify our understanding of existing species concepts. We describe three new species (Xerocomellus atropurpureus, X. diffractus, and X. salicicola) and propose two new combinations (X. amylosporus and X. mendocinensis), transfer Boletus coccyginus to Hortiboletus, and provide a dichotomous key to species of Xerocomellus in western North America.

Patients with liver cirrhosis (LC) are at an increased risk for postoperative complications after open inguinal hernia repair (OIHR). It is possible that orthotopic liver transplant (OLT) recipients may have better outcomes, given reversal of liver failure pathophysiology. Therefore, we sought to compare mortality risk, complications, length of stay (LOS), and cost associated with OIHR in OLT recipients versus LC. From the National Inpatient Sample (NIS), using ICD-9 codes, we found 83 OLT recipients and 764 patients with LC who underwent OIHR between 2002 and 2014. We used logistic, negative binomial, and multiple linear regression models to compare peri-operative mortality risk, postoperative complications, and LOS, and cost associated with OIHR in OLT recipients versus LC patients. Models were adjusted for patient demographic and clinical characteristics, and hospital factors. OLT recipients were younger (58 vs 61, p = 0.02), more likely to be privately insured (42.0% vs 24.6%, p = 0.006), less likely to have ascites at time of surgery (5.1% vs 18.9%, p = 0.003), and have surgery at large (84.3% vs 65.2%, p = 0.01) and teaching hospitals (84.2% vs 47.9%, p

The primary aim of this study was to explore different methods of inducing self-compassion in individuals with elevated social anxiety. Three methods of inducing self-compassion were compared as follows: a writing tool, an audio meditation, and an interview. Participants (N = 167; students with high social anxiety) were asked to write about a social situation in which they felt judged and were then randomly assigned to one of the three induction conditions or a control condition. Subsequently, state self-compassion was assessed. Participants reported significantly higher state self-compassion in the written condition than both the interview and control conditions (η2 = 0.10, medium effect). The present study informs future work examining the impact of self-compassion inductions on social anxiety outcomes, suggesting the continued use of written self-compassion inductions.

Reflective journaling is common practice in teacher preparation and often utilized as a tool to cultivate teacher candidates’ dispositional development. This paper details a study that implemented ...

Histone variants play a crucial role in chromatin structure organization and gene expression. Trypanosomatids have an unusual H2B variant (H2B.V) that is known to dimerize with the variant H2A.Z generating unstable nucleosomes. Previously, we found that H2B.V protein is enriched in nonreplicative life forms of Trypanosoma cruzi, suggesting that this variant may contribute to the differences in chromatin structure and global transcription rates observed among parasite life forms. Here, we performed the first genome-wide profiling of histone localization in T. cruzi using replicative and nonreplicative life forms, and we found that H2B.V was preferentially located at the edges of divergent switch regions, which encompass putative transcriptional start regions; at some tDNA loci; and between the conserved and disrupted genome compartments, mainly at trans-sialidase, mucin and MASP genes. Remarkably, the chromatin of nonreplicative forms was depleted of H2B.V-enriched peaks in comparison to replicative forms. Interactome assays indicated that H2B.V associated specifically with H2A.Z, bromodomain factor 2, nucleolar proteins and a histone chaperone, among others. Parasites expressing reduced H2B.V levels were associated with higher rates of parasite differentiation and mammalian cell infectivity. Taken together, H2B.V demarcates critical genomic regions and associates with regulatory chromatin proteins, suggesting a scenario wherein local chromatin structures associated with parasite differentiation and invasion are regulated during the parasite life cycle.Author SummaryTrypanosomatids have to adapt to different environmental conditions, changing their morphology, gene expression and metabolism. These organisms have many unique features in terms of gene expression regulation. The genomic organization includes polycistronic regions with the absence of well-defined transcription start sites. In T. brucei, histone variants mark the start and ending sites of transcription; however, little is known about whether these proteins change their genome location, expression levels and interactors along life forms and what the impact is of these changes on parasite differentiation and infection. In T. cruzi, the causative agent of Chagas disease, we previously found that the histone variant of H2B is enriched in nonreplicative and infective forms, suggesting that this variant may contribute to the differences in chromatin structure and global transcription rates observed among these life forms. Here, we aimed to go one step further and performed the first histone ChIP-seq analysis in T. cruzi, in which we found that H2B.V was enriched at divergent strand switch regions, some tDNA loci and other critical genomic regions associated with T. cruzi genome compartments. We found that H2B.V interacts with a bromodomain factor, suggesting an intricate network involving chromatin acetylation around H2B.V enriched sites. Moreover, parasites expressing reduced H2B.V levels were associated with higher rates of differentiation and mammalian cell infectivity.

The Employment Equality Framework Directive (EED) is the first and still the only EU law that requires EU member states to combat sexual orientation discrimination. It requires states to change employment laws or draft news ones that prevent employers and coworkers from discriminating against gay and lesbian employees. Implementation of the EED was problematic, despite strong support for the law among many EU member states and their publics. An analysis of the EED’s provisions shows that in countries where religious organizations provide a substantial share of a country’s social services, governments are more likely to transpose the directive incorrectly. These findings are based on an innovative research design that addresses one legal subject matter within a directive. Contradicting earlier research showing it has little to no role, public opinion about an EU law can affect compliance. This article also sheds more light on how religious organizations and beliefs affect European integration, comparatively understudied in the literature. These findings also have important implications for the future of lesbian, gay, bisexual and transgender (LGBT) human rights legislation at the EU level.

Replicated clinical trials have demonstrated rapid and robust antidepressant effects with ketamine in treatment resistant mood disorders. Sex (biological) and gender differences in therapeutic effects for any new intervention is an important consideration, however, the differential efficacy, safety and tolerability of ketamine in males versus females remains underexplored. The objective of the present systematic review is to identify and qualitatively synthesize all published clinical studies relevant to the sex differential effects of ketamine for mood disorders. A systematic search of PubMed, Medline, and PsycInfo from inception until January 20, 2021, yielded 27 reports including 1715 patients (742 males and 973 females) that met inclusion criteria. Results from the vast majority of studies (88.8%) do not support significant sex differences in antidepressant response, tolerability or safety of ketamine. Nine (33.3%) of the reports included a bioanalytical component in the analysis and only one reported on sex differences. Evidence from the present review does not support clinically or statistically significant sex differences in therapeutic effects with ketamine. Nevertheless, future studies should continue to consider sex and biological sex differences in study design and data analytic plans.

Many eukaryotic organisms are diploid or even polyploid, i.e. they harbour two or more independent copies of each chromosome. Yet, to date most reference genome assemblies represent a mosaic consensus sequence in which the homologous chromosomes have been collapsed into one sequence. This procedure generates sequence artefacts and impedes analyses of allele-specific mechanisms. Here, we report the allele-specific genome assembly of the diploid unicellular protozoan parasite Trypanosoma brucei.As a first step, we called variants on the allele-collapsed assembly of the T. brucei Lister 427 isolate using short-read error-corrected PacBio reads. We identified 96 thousand heterozygote variants across the genome (average of 4.2 variants / kb), and observed that the variant density along the chromosomes was highly uneven. Several long (>100 kb) regions of loss-of-heterozigosity (LOH) were identified, suggesting recent recombination events between the alleles. By analysing available genomic sequencing data of multiple Lister 427 derived clones, we found that most LOH regions were conserved, except for some that were specific to clones adapted to the insect lifecycle stage. Surprisingly, we also found that some Lister 427 clones were aneuploid. We found evidence of trisomy in chromosome five (chr 5), chr 2, chr 6 and chr 7. Moreover, by analysing RNA-seq data, we showed that the transcript level is proportional to the ploidy, evidencing the lack of a general expression control at the transcript level in T. brucei.As a second step, to generate an allele-specific genome assembly, we used two powerful datatypes for haplotype reconstruction: raw long reads (PacBio) and chromosome conformation (Hi-C) data. With this approach, we were able to assign 99.5% of all heterozygote variants to a specific homologous chromosome, building a 66 Mb long T. brucei Lister 427 allele-specific genome assembly. Hereby, we identified genes with allele-specific premature termination codons and showed that differences in allele-specific expression at the level of transcription and translation can be accurately monitored with the fully phased genome assembly.The obtained reference-grade allele-specific genome assembly of T. brucei will enable the analysis of allele-specific phenomena, as well as the better understanding of recombination and evolutionary processes. Furthermore, it will serve as a standard to ‘benchmark’ much needed automatic genome assembly pipelines for highly heterozygous wild species isolates.

Title PageManuscript TitleComment on: “A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib”Authors:Alana Slomovic, M.D., Pediatric Resident, Department of Pediatrics, Cohen Children’s Medical CenterTerry Amaral, M.D., Associate Chief - Division of Orthopedic Surgery, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellIgor Lobko, M.D., Chief – Division of Vascular/ Interventional Radiology, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellDavid Siegel, M.D., Executive Vice Chairman – Department of Radiology, Long Island Jewish Medical Center, Associate Professor, Zucker School of Medicine at Hofstra/ NorthwellRachelle Goldfisher, M.D., Division of Pediatric Radiology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellRachel Kessel, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCarolyn Fein Levy, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCorresponding Author: Carolyn Fein Levy, M.D.269-01 76th Avenue, Suite 255New Hyde Park, NY 11040Phone: (718) 470 3460Fax: (718) 343 4642 email: clevy4@northwell.eduMain text word count: 564 wordsNumber of figures: 1Short running title: Infantile fibrosarcoma treated with larotrectinibKey Words: Infantile fibrosarcoma, Larotrectinib, NTRK fusionAbbreviations Key

Posté le 28 janvier 2020 sur BioRxiv https://www.biorxiv.org/content/10.1101/2020.01.27.921452v1; Highly selective gene expression is a key requirement for antigenic variation in several pathogens, allowing evasion of host immune responses and maintenance of persistent infections. African trypanosomes, parasites that cause lethal diseases in humans and livestock, employ an antigenic variation mechanism that involves monogenic antigen expression from a pool of >2500 antigen coding genes. In other eukaryotes, the expression of individual genes can be enhanced by mechanisms involving the juxtaposition of otherwise distal chromosomal loci in the three-dimensional nuclear space. However, trypanosomes lack classical enhancer sequences or regulated transcription initiation and the monogenic expression mechanism has remained enigmatic. Here, we show that the single expressed antigen coding gene displays a specific inter-chromosomal interaction with a major mRNA splicing locus. Chromosome conformation capture (Hi-C), revealed a dynamic reconfiguration of this inter-chromosomal interaction upon activation of another antigen. Super-resolution microscopy showed the interaction to be heritable and splicing dependent. We find that the two genomic loci are connected by the antigen exclusion complex, whereby VEX1 associated with the splicing locus and VEX2 with the antigen coding locus. Following VEX2 depletion, loss of monogenic antigen expression was accompanied by increased interactions between previously silent antigen genes and the splicing locus. Our results reveal a novel mechanism to ensure monogenic expression, requiring the spatial integration of antigen transcription and mRNA splicing in a dedicated compartment. These findings suggest a new means of post-transcriptional gene regulation.

The knee menisci are prone to mechanical fatigue injury from the cyclic tensile stresses that are generated during daily joint loading. Here we characterize the tensile fatigue behavior of human medial meniscus and investigate the effect of aging on fatigue strength. Test specimens were excised from the medial meniscus of young (under 40 years) and older (over 65 years) fresh-frozen cadaver knees. Cyclic uniaxial tensile loads were applied parallel to the primary circumferential fibers at 70%, 50%, 40%, or 30% of the predicted ultimate tensile strength (UTS) until failure occurred or one million cycles was reached. Equations for fatigue strength (S-N curve) and the probability of fatigue failure (unreliability curves) were created from the measured number of cycles to failure. The mean number of cycles to failure at 70%, 50%, 40%, and 30% of UTS were estimated to be approximately 500, 40000, 340000, and 3 million cycles, respectively. The endurance limit, defined as the tensile stress that can be safely applied for the average lifetime of use (250 million cycles), was estimated to be 10% of UTS (∼1.0 MPa). When cyclic tensile stresses exceeded 30% of UTS (∼3.0 MPa), the probability of fatigue failure rapidly increased. While older menisci were generally weaker and more susceptible to fatigue failures at high-magnitude tensile stresses, both young and older age groups had similar fatigue resistance at low-magnitude tensile stresses. In addition, we found that fatigue failures occurred after the dynamic modulus decreased during cyclic loading by approximately 20%. This experimental study has quantified fundamental fatigue properties that are essential to properly predict and prevent injury in meniscus and other soft fibrous tissues.

This paper investigates what affects the views of parliamentary candidates on gay rights, independent of public opinion. Because in most parliamentary systems parties select their candidates, we would expect political ideology to play a strong role in shaping their views. However, drawing on rarely used data on the views and background of thousands of individual parliamentary candidates from countries across Europe and their policy preferences on the issue of same-sex marriage, our results show that political ideology and partisanship do not tell the whole story. Empirically, we demonstrate that parliamentary candidates’ positions on same-sex marriage are determined more by their religious beliefs and other socio-demographic characteristics than by political ideology, even within parties traditional supportive of progressive social values. This study contributes to better understanding how LGBTQ policy change happens in Europe by examining the preferences of the people mainly responsible for it.

The knee meniscus is a soft fibrous tissue with a high incidence of injury in older populations. The objective of this study was to determine the effect of age on the failure behavior of human knee meniscus when applying uniaxial tensile loads parallel or perpendicular to the primary circumferential fiber orientation. Two age groups were tested: under 40 and over 65 years old. We paired high-speed video with digital image correlation to quantify for the first time the planar strains occurring in the tear region at precise time points, including at ultimate tensile stress, when the tissue begins losing load-bearing capacity. On average, older meniscus specimens loaded parallel to the fiber axis had approximately one-third less ultimate tensile strain and absorbed 60% less energy to failure within the tear region than younger specimens (p 0.05). Older specimens also had significantly reduced strength and material toughness when loaded perpendicular to the fibers (p 0.05). These age-related changes indicate a loss of collagen fiber extensibility and weakening of the non-fibrous matrix with age. In addition, we found that when loaded perpendicular to the circumferential fibers, tears propagated near the planes of maximum tensile stress and strain. Whereas when loaded parallel to the circumferential fibers, tears propagated oblique to the loading axis, closer to the planes of maximum shear stress and strain. Our experimental results can assist the selection of valid failure criteria for meniscus, and provide insight into the effect of age on the failure mechanisms of soft fibrous tissue.

Patients with liver cirrhosis (LC) are at an increased risk for postoperative complications after open inguinal hernia repair (OIHR). It is possible that orthotopic liver transplant (OLT) recipients may have better outcomes, given reversal of liver failure pathophysiology. Therefore, we sought to compare mortality risk, complications, length of stay (LOS), and cost associated with OIHR in OLT recipients versus LC.From the National Inpatient Sample (NIS), using ICD-9 codes, we found 83 OLT recipients and 764 patients with LC who underwent OIHR between 2002 and 2014. We used logistic, negative binomial, and multiple linear regression models to compare peri-operative mortality risk, postoperative complications, and LOS, and cost associated with OIHR in OLT recipients versus LC patients. Models were adjusted for patient demographic and clinical characteristics, and hospital factors.OLT recipients were younger (58 vs 61, p = 0.02), more likely to be privately insured (42.0% vs 24.6%, p = 0.006), less likely to have ascites at time of surgery (5.1% vs 18.9%, p = 0.003), and have surgery at large (84.3% vs 65.2%, p = 0.01) and teaching hospitals (84.2% vs 47.9%, p 0.001). There were no mortalities among OLT recipients, but 19 (2.5%) deaths among LC patients. OLT recipients had a similar risk of overall complications (adjusted odds ratio aOR = 0.71 1.30 2.41) and hospital-associated costs (adjusted cost ratio = 0.71 0.88 1.09). However, LOS was significantly different with OLT recipients having shorter LOS (adjusted LOS ratio = 0.56 0.70 0.89).Delaying OIHR in patients with LC until after OLT decreases LOS and may carry decreased mortality.

Equal treatment for members of the lesbian, gay, bisexual, and transgender (LGBT) community has improved at a rapid pace around the world since the gay rights movement first rose up to become a salient global force for change. With important regional exceptions, laws criminalizing same-sex sexual relations have not only come down in multiple countries, but same-sex couples can now also construct families in many advanced industrialized countries. Public acceptance of homosexuality, even in some non-Western countries, has increased dramatically. Yet, within those general trends hides the remarkable unevenness in the spread and adoption of policies fostering legal, social, and economic equality for LGBTQ communities around the world. Policy change toward more equal treatment for sexual minorities is concentrated in the developed world and within the cisgender gay and lesbian communities in particular. The existing literature in policy change shows the importance of transnational activists, changing international norms, and increasing levels of secularization have made this possible. But the effectiveness of these factors rests on an underlying foundation of socioeconomic factors based on economic and social development that characterizes advanced industrialized states. There is an uneven distribution of resources and interests among pro and anti-LGBT activist groups alike, and the differing levels of economic development in which they operate that explains the decidedly uneven nature of how LGBTQ human rights have advanced in the past 50 years. In addition, new political parties and activist organizations have emerged to lead the backlash against LGBTQ rights, showing progress is neither inevitable nor linear. In addition, serious gaps in what we know about LGBT politics remain because of the overwhelming scholarly focus on advanced industrialized states and policies that benefit the cisgender, gay and lesbian middle class in primarily Western societies. The study of LGBT politics in non-Western and developing countries is woefully neglected, for reasons attributed to the nature of the research community and the subject area. In the developed world, greater attention is needed to inequality within the LGBTQ community and issues beyond same-sex marriage. Finally, issues of intersectionality and how different groups within the LGBT community have enjoyed most of the benefits of the gay rights movement since its takeoff more than 50 years ago.

Why are European Jews migrating to Israel in significant numbers? Israeli leaders and popular press reports suggest that incidents of antisemitism have reached such high levels across Europe, even ...

Although a growing number of European governments have legalized same-sex civil unions (SSU) and same-sex marriage (SSM) in the past two decades, others have moved in the opposite direction by stal...

The Employment Equality Directive expands protections for, among others, gays and lesbians from discriminatory employment practices. This directive has been implemented poorly in Ireland, the UK, and Germany, because religious organizations believed their core ideological and material interests were threatened by extending these protections, even though degrees of policy fit vary among all three countries. Furthermore, the European Commission’s enforcement measures have not been effective in securing compliance. The European Commission has permitted noncompliance to continue in Ireland and the UK. Only change in the partisan make-up of the government led to compliance. This article speaks to ongoing debates about the causes of noncompliance with European Union law and how religious groups, not often considered in the scholarly literature, are now trying to limit the effects of European integration

Objective To determine the impact of skin-to-tumor (STT) distance on the risk for treatment failure following percutaneous cryoablation (PCA). Methods We retrospectively reviewed patients who underwent PCA with documented T1a recurrent renal cell carcinoma (RCC) at 2 academic centers between 2005 and 2015. Patient demographics, tumor characteristics, and perioperative and postoperative course variables were collected. Additionally, we measured the STT distance by averaging the distance from the skin to the center of the tumor at 0°, 45°, and 90° on preoperative computed tomography imaging. Results We identified 86 patients with documented T1a RCC. The mean age at the time of surgery was 69 years (range: 37-91 years), and the mean tumor size was 2.7 cm (range: 1.0-4.0 cm). With a mean follow-up of 24 months (range: 3-63 months), 11 (12.8%) treatment failures occurred. Patients with treatment failure had significantly higher mean STT distance than those without: 11.0 cm (range: 6.3-20.1 cm) compared to 8.4 cm (range: 4.4-15.2 cm), respectively (P = .002). STT distance was an independent predictor of treatment failure (odds ratio: 1.32, 95% confidence interval: 1.04-1.69, P = .029). STT distance greater than 10 cm had a fourfold increased risk of tumor treatment failure (odds ratio: 4.43, 95% confidence interval: 1.19-16.39, P = .018). Tumor size, R.E.N.A.L. Nephrometry score, and number of cryoprobes placed were not associated with treatment failure. Conclusion STT, an easily measured preoperative variable, may inform the risk of RCC treatment failure following PCA.

Students with disabilities continue to be denied literacy rich experiences with their non-disabled peers. Throughout this article the authors explore how narrow, ability-focused teacher dispositions can perpetuate low expectations and can preemptively deny students with disabilities access to meaningful literacy experiences. Hence, the development of an inclusive literacy disposition is crucial to providing access to robust learning experiences for students with disabilities. The authors describe a research study that utilizes journal writing and a role-play intervention with pre-service general educators in a graduate literacy methods course. Analysis of post-intervention data suggests it is possible to shift narrow, ability-orientated dispositions to broader and more inclusive conceptualizations that support students with disabilities. Implications for both research and practice are discussed.

This retrospective study presents three consecutive patients who underwent bilateral ureteral occlusion using the Amplatzer vascular plugs and N-butyl cyanoacrylate glue sandwich method. The patients were 63- and 65-year-old males and a 79-year-old female. Indications for the procedure included severe cystitis and complex vesicular fistulas unresponsive to urinary diversion. All three patients had immediate resolution of urinary leakage, resulting in symptom relief throughout the follow-up period. There were no procedure-related complications or side effects.

Intrahepatic portosystemic venous shunts (IPSVSs) are rare vascular malformations. They can be asymptomatic or present with various symptoms including encephalopathy. We present two cases of IPSVS, one involving a patient presenting with altered mental status and the other discovered incidentally. While there is no question that patients presenting with symptomatic IPSVS should undergo definitive treatment, there is no consensus regarding elective therapy for asymptomatic lesions.

Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health.We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis.Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment.Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management.

AUR = acute urinary retention, BOO = bladder outlet obstruction, BPH = benign prostatic hyperplasia, FDA = U.S. Food and Drug Administration, IDE = investigational device exemption, IPSS = International Prostate Symptom Score, LUTS = lower urinary tract symptoms, PAE = prostatic artery embolization, PV = prostate volume, QOL = quality of life, TUMT = transurethral microwave thermotherapy, TURP = transurethral resection of the prostate, RCP = research consensus panel, UTI = urinary tract infection

Gonadal vein angioembolization is a successful means of primary and salvage treatment for symptomatic varicoceles. We aim to investigate angiographic findings during embolization of primary varicoceles vs those with failed surgical ligation.Between 1992 and 2010, 106 cases referred to our interventional radiologists for primary or salvage varicocelectomy were reviewed. These patients underwent venography and gonadal vein embolization using a combination of embolization coils and vascular plugs. All images were reviewed by an interventional radiologist to determine the anatomic etiology of the varicocele. Primary and salvage embolization cohorts were compared using t test and chi-square analyses for continuous and categorical variables, respectively. Angiographic parameters were analyzed using univariate and multivariable regression models to determine significance in predicting primary vs salvage status.Of the 106 patients, 46 patients (57 testicles) underwent primary and 60 patients (62 testicles) underwent salvage embolization. The salvage cohort of patients was younger (P0.001) and comprised more solely left-sided pathology (P=0.002). An equivalent number of gonadal vein divisions and proportion of patent gonadal veins was found. However, there was a significantly higher proportion (27.8% vs 6.7%) of inguinal collateral vessels and combined presence of inguinal and retroperitoneal collateral veins (8.5% vs 2.1%) identified in the cohort undergoing embolization after failed surgical varicocelectomy. Presence of inguinal collaterals (P=0.008) as well as presence of both inguinal and retroperitoneal collaterals (P=0.038) on multivariable regression analysis revealed both as independent prognosticators of salvage status.Recurrence after surgical varicocelectomy is associated with increased inguinal collaterals. The pitfall presented by this anatomic variant to surgical ligation may be successfully managed with selective gonadal vein embolization.

Biomarkers are important tools for identifying and stratifying diseases, predicting their progression and determining the effectiveness, safety, and doses of therapeutic interventions. This is important for common chronic diseases such as diabetic nephropathy, osteoporosis, and rheumatoid arthritis which affect large numbers of patients worldwide. This article summarizes the current knowledge of established and novel biomarkers for each of these diseases as presented at the 2008 AAPS/ACCP joint symposium “Success Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications,” in Atlanta, Georgia. The advantages and disadvantages of various proteomic, metabolomic, genomic, and imaging biomarkers are discussed in relation to disease diagnosis and stratification, prognosis, drug development, and potential clinical applications. The use of biomarkers as a means to determine therapeutic interventions is also considered. In addition, we show that biomarkers may be useful for adapting therapies for individual needs by allowing the selection of patients who are most likely to respond or react adversely to a particular treatment. They may also be used to determine whether the development of a novel therapy is worth pursuing by informing crucial go/no go decisions around safety and efficacy. Indeed, regulatory bodies now suggest that effective integration of biomarkers into clinical drug development programs is likely to promote the development of novel therapeutics and more personalized medicine.

Percutaneous surgery is an established approach to a spectrum of renal pathology, and hemorrhage is the most concerning complication of this technique. We determined the frequency of postoperative hemorrhage requiring selective angioembolization (sae), the efficacy of this approach, and characterized the angiographic findings.We reviewed our database of 4695 patients who underwent percutaneous renal surgery and identified patients requiring SAE for postoperative hemorrhage. Angiographic findings were recorded and efficacy of SAE documented.Patients undergoing percutaneous stone extraction (PSE; 3685), percutaneous antegrade endopyelotomy (PAE; 850), and upper-tract transitional cell carcinoma (UTTCC) resection (160) were reviewed. We identified 57 patients requiring SAE (1.2%) who underwent 44 PSEs (77.2%), 7 PAEs (12.3%), and 6 UTTCC resections (10.5%). This represented 1.2%, 0.8%, and 3.2% of all PSE, PAE, and UTTCC resections, respectively. Angiography revealed treatable lesions in 94.7% of patients. Overall, 64 angiographic findings were encountered including 30 pseudoaneurysms (53% of patients, 47% of findings), 14 arteriovenous fistulas (AVFs) (25% of patients, 22% of findings), and 14 instances of contrast extravasation (25% of patients, 22% of findings). Two arterial dissections and one instance each of a hypervascular area, a vascular "cut-off" sign, and a fistula between an artery and the percutaneous tract were identified. One bleeding vessel identified at the base of a UTTCC resection was not amenable to embolization. Ten patients (17.5%) hador=1 angiographic finding. Three patients (5.3%) had no angiographic findings to account for hemorrhage. No angioembolization-related complications occurred. Complete resolution of bleeding was observed in 54 patients (95%).Major hemorrhage requiring intervention after percutaneous renal surgery is uncommon. The most common angiographic finding is arterial pseudoaneurysm, followed by arteriovenous fistula, and contrast extravasation. In 95% of cases angiography reveals a demonstrable and treatable etiology. This strongly supports the first-line use of angiography for intractable bleeding in this setting.