Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration-Resistant Prostate Cancer.

Purpose: PD-L1 is overexpressed by dendritic cells in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on androgen receptor pathway inhibitors. We tested whether checkpoint blockade could enhance antitumor activity in mCRPC.

Patients And Methods: In a multicenter open-label noncomparative randomized phase II study, patients with mCRPC treated with ≤1 prior cytotoxic chemotherapy, with measurable disease and progression on abiraterone and/or enzalutamide, were randomized to durvalumab 1,500 mg intravenously every 4 weeks ±4 doses of tremelimumab 75 mg intravenously.

Correction: Late date of human arrival to North America: Continental scale differences in stratigraphic integrity of pre-13,000 BP archaeological sites.

[This corrects the article DOI: 10.1371/journal.pone.

Rucaparib or Physician's Choice in Metastatic Prostate Cancer.

Background: In a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with a deleterious alteration. Data are needed to confirm and expand on the findings of the phase 2 study.

Methods: In this randomized, controlled, phase 3 trial, we enrolled patients who had metastatic, castration-resistant prostate cancer with a , , or alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI).

Late date of human arrival to North America: Continental scale differences in stratigraphic integrity of pre-13,000 BP archaeological sites.

By 13,000 BP human populations were present across North America, but the exact date of arrival to the continent, especially areas south of the continental ice sheets, remains unclear. Here we examine patterns in the stratigraphic integrity of early North American sites to gain insight into the timing of first colonization. We begin by modeling stratigraphic mixing of multicomponent archaeological sites to identify signatures of stratigraphic integrity in vertical artifact distributions.

Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial.

Background: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting.

Patients And Methods: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria).

Moving forward after cancer: successful implementation of a colorectal cancer patient-centered transitions program.

Purpose: Cancer survivors transitioning between academic comprehensive cancer systems and community general practice settings are vulnerable to discontinuity, inconsistency and variation in care, inappropriate surveillance testing, and a sense of isolation and loss. Though these issues have been well recognized for over a decade and a half in the survivorship, oncologic, and health services literature, there remains a dearth of positive examples of models that have been well received by both the transitioned patient and the providers on either side of the handoff. We herein describe a sustained positive example of a transitions program.

Baseline Edmonton Symptom Assessment System and survival in metastatic renal cell carcinoma.

Background: Baseline symptom burden as measured using the Edmonton Symptom Assessment System (esas), a patient-reported, validated, and reliable tool measuring symptom severity in 9 separate domains, might yield prognostic information in patients receiving treatment for metastatic renal cell carcinoma (mrcc) and might add to the existing prognostic models.

Methods: In this retrospective single-centre cohort study, we included patients receiving first-line sunitinib therapy for mrcc between 2008 and 2012. Baseline variables included information relevant to the pre-existing prognostic models and pre-treatment esas summation scores (added together across all 9 domains), with higher scores representing greater symptom burden.

Atrial Antitachycardia Pacing in Complex Congenital Heart Disease: A Case Series.

Among the congenital heart disease (CHD) population, intra-atrial reentrant tachycardia (IART) is a common sequela resulting from anatomical anomalies and surgical scars that significantly increases morbidity and mortality. Atrial antitachycardia pacing (ATP) delivered by atrial antitachycardia devices (ATDs) has been used to treat IART in the CHD population. However, there remains limited data on the safety and efficacy of ATP, as well as on comparisons of its effects amongst different CHD subtypes.

A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic castration resistant prostate cancer.

Purpose Heat shock protein 27 (Hsp27) is implicated in prostate cancer progression. Apatorsen is a second generation phosphorothioate antisense inhibitor of Hsp27 expression. We evaluated apatorsen in patients with metastatic castration resistant prostate cancer (mCRPC).

Safety and efficacy of atrial antitachycardia pacing in congenital heart disease.

Background: Intra-atrial reentrant tachycardia (IART) is a common sequela in the congenital heart disease (CHD) population, and it significantly increases morbidity and mortality. Atrial antitachycardia devices (ATDs) capable of atrial antitachycardia pacing (ATP) therapy have been used to manage IART in the CHD population, but there are limited data on their safety and efficacy.

Objectives: To determine whether ATD implantation was associated with reduced direct current (DC) cardioversions and to compare ATP success between different CHD diagnoses and ATP programs.

Contralateral axillary lymph node metastasis in second primary Breast cancer: Case report and review of the literature.

The rare entity of contra-lateral axillary lymph node metastasis(CAM) has been a debatable topic in the realm of breast cancer management for many years. There remains controversy over whether CAM should be considered distant metastasis or locoregional spread. It is also uncertain why or how CAM occurs.

Tracing social interactions in Pleistocene North America via 3D model analysis of stone tool asymmetry.

Stone tools, often the sole remnant of prehistoric hunter-gatherer behavior, are frequently used as evidence of ancient human mobility, resource use, and environmental adaptation. In North America, studies of morphological variation in projectile points have provided important insights into migration and interactions of human groups as early as 12-13 kya. Using new approaches to 3D imaging and morphometric analysis, we here quantify bifacial asymmetry among early North American projectile point styles to better understand changes in knapping technique and cultural transmission.

Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair.

De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction.

Transgenic rodent assay for quantifying male germ cell mutant frequency.

De novo mutations arise mostly in the male germline and may contribute to adverse health outcomes in subsequent generations. Traditional methods for assessing the induction of germ cell mutations require the use of large numbers of animals, making them impractical. As such, germ cell mutagenicity is rarely assessed during chemical testing and risk assessment.

Remote monitoring of cardiovascular implantable devices in the pediatric population improves detection of adverse events.

With the exponential growth of cardiovascular implantable electronic devices (CIEDs) in pediatric patients, a new method of long-term surveillance, remote monitoring (RM), has become the standard of care. The purpose of this study was to determine the usefulness of RM as a monitoring tool in the pediatric population. A retrospective review was performed of 198 patients at the University of Iowa Children's Hospital who had CIEDs.

No evidence for transgenerational genomic instability in the F1 or F2 descendants of Muta™Mouse males exposed to N-ethyl-N-nitrosourea.

Exposure of male mice to genotoxic agents can increase mutation frequencies in their unexposed descendants. This phenomenon, known as transgenerational genomic instability (TGI), can persist for several generations. However, little is known about the underlying mechanisms.

Simultaneous measurement of benzo[a]pyrene-induced Pig-a and lacZ mutations, micronuclei and DNA adducts in Muta™ Mouse.

In this study we compared the response of the Pig-a gene mutation assay to that of the lacZ transgenic rodent mutation assay, and demonstrated that multiple endpoints can be measured in a 28-day repeat dose study. Muta™Mouse were dosed daily for 28 days with benzo[a]pyrene (BaP; 0, 25, 50 and 75 mg/kg body weight/day) by oral gavage. Micronucleus (MN) frequency was determined in reticulocytes (RETs) 48 hr following the last dose.

A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy.

For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life.

Mutagenicity of carbon nanomaterials.

Carbon nanomaterials such carbon nanotubes, graphene and fullerenes are some the most promising nanomaterials. Although carbon nanomaterials have been reported to possess genotoxic potential, it is imperitive to analyse the data on the genotoxicity of carbon nanomaterials in vivo and in vitro and check the validity and predictability of different assays.

Nonfluoroscopic and radiation-limited ablation of ventricular arrhythmias in children and young adults: a case series.

The purpose of this study was to report the feasibility and procedural technique of minimal or no fluoroscopy in the ablation of ventricular arrhythmias in the pediatric population. A retrospective review was performed of all patients <21 years old who underwent ablation of ventricular arrhythmias using three-dimensional (3D) mapping with no or minimal fluoroscopy at a single institution. Five patients underwent electrophysiology studies for ventricular tachycardia or frequent premature ventricular complexes.

Mutation spectrum in FE1-MUTA(TM) Mouse lung epithelial cells exposed to nanoparticulate carbon black.

It has been shown previously that carbon black (CB), Printex 90 exposure induces cII and lacZ mutants in the FE1-Muta(TM) Mouse lung epithelial cell line and causes oxidatively damaged DNA and the production of reactive oxygen species (ROS). The purpose of this study was to determine the mutation spectrum in the cII gene of Printex 90 exposed cells. Cells exposed to CB have a substantially different mutation spectrum in the cII gene compared with vehicle exposed controls.

Successful transcatheter cryoablation in infants with drug-resistant supraventricular tachycardia: a case series.

Purpose: Drug-resistant supraventricular tachycardia can cause hemodynamic instability, especially in infants. There are no case-series reports of transcatheter cryoablation treatment for infants with drug-resistant supraventricular tachycardia. Our purpose is to report our experience with transcatheter cryoablation in three infants with drug-resistant supraventricular tachycardia.