A new screener predicts Toddlers' language development from age 2-3: The QUILS:TOD.

Language interventions may yield greater benefits for younger children than their older counterparts, making it critical to evaluate children's language skills as early as possible. Yet, assessing young children's language presents many challenges, such as limited attention spans, low expressive language, and hesitancy to speak with an unfamiliar examiner. To address these challenges, the Quick Interactive Language Screener for Toddlers (QUILS:TOD; for children 24- to 36-months of age) was developed as a quick, tablet-based language screener capable of assessing children's vocabulary, syntax, and word learning skills.

The PIWI/piRNA response is relaxed in a rodent that lacks mobilizing transposable elements.

Transposable elements (TEs) are genomic parasites that can propagate throughout host genomes. Mammalian genomes are typically dominated by LINE retrotransposons and their associated SINEs, and germline mobilization is a challenge to genome integrity. There are defenses against TE proliferation and the PIWI/piRNA defense is among the most well understood.

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE).

Phase 1b Trial of Biweekly Intravenous Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus in Colorectal Cancer.

Fifteen patients with treatment-refractory colorectal cancer were enrolled on a phase 1b study of Pexa-Vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia designed to selectively replicate in cancer cells. Pexa-Vec was administered intravenously every 14 days, at dose levels of 1 × 10(6), 1 × 10(7), or 3 × 10(7) plaque-forming units (pfu)/kg. The primary endpoint was to determine the maximum tolerated dose.

Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer.

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n=30).

Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans.

Efforts to selectively target and disrupt established tumor vasculature have largely failed to date. We hypothesized that a vaccinia virus engineered to target cells with activation of the ras/MAPK signaling pathway (JX-594) could specifically infect and express transgenes (hGM-CSF, β-galactosidase) in tumor-associated vascular endothelial cells in humans. Efficient replication and transgene expression in normal human endothelial cells in vitro required either VEGF or FGF-2 stimulation.

Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans.

The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours.

Sequential therapy with JX-594, a targeted oncolytic poxvirus, followed by sorafenib in hepatocellular carcinoma: preclinical and clinical demonstration of combination efficacy.

JX-594 is a targeted and granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In a phase 1 trial, JX-594 injection into hepatocellular carcinoma (HCC) was well-tolerated and associated with viral replication, decreased tumor perfusion, and tumor necrosis. We hypothesized that JX-594 and sorafenib, a small molecule inhibitor of B-raf and vascular endothelial growth factor receptor (VEGFR) approved for HCC, would have clinical benefit in combination given their demonstrated efficacy in HCC patients and their complementary mechanisms-of-action.

Quantitative imaging test approval and biomarker qualification: interrelated but distinct activities.

Unlabelled: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers.

Alkaline pulping of some eucalypts from Sudan.

Four eucalypts (Eucalyptus camaldulensis, Eucalyptus microtheca, Eucalyptus tereticornis and Eucalyptus citriodora) grown in Sudan were examined for their suitability for pulping and papermaking with different alkaline methods. Their physical, morphological and chemical characteristics are reported. The pulping trials with E.

International investigation of breast MRI: results of a multicentre study (11 sites) concerning diagnostic parameters for contrast-enhanced MRI based on 519 histopathologically correlated lesions.

A multicentre study was undertaken to provide fundamentals for improved standardization and optimized interpretation guidelines of dynamic contrast-enhanced MRI. Only patients scheduled for biopsy of a clinical or imaging abnormality were included. They underwent standardized dynamic MRI on Siemens 1.

Neural blockade for abdominopelvic pain of oncologic origin.

Neural blockade, like other accepted treatments for persistent pain, is not a panacea. Careful assessment is required to elicit the need for complementary interventions, including pharmacological management and psychobehavioral and rehabilitative approaches, combined with attention to the palliation of other symptoms. Celiac and superior hypogastric plexus blocks are well-accepted, effective, and minimally hazardous means for providing palliation of visceral abdominopelvic pain.

Pain and loss of function in head and neck cancer survivors.

Head and neck cancers are relatively uncommon malignancies and the characteristics of pain and functional impairments in survivors are not well studied. To characterize the incidence, location, severity, types and causes of pain; associated functional impairments, and pain management methods, the medical charts of 40 consecutive outpatients with biopsy-proven head and neck cancers were reviewed. Pain was severe in 52% (N = 21), and was located near sites of tumor origin.

Complex renal cysts: findings on MR imaging.

Objective: We retrospectively evaluated our experience with complex cystic renal masses on MR imaging, using T1-weighted, T2-weighted, and gadolinium-enhanced images, to determine whether imaging features could permit distinction between benign and malignant lesions.

Materials And Methods: Thirty-seven patients with complex cystic renal lesions were included in this retrospective study. The patients selected had undergone T1-weighted, T2-weighted, and gadolinium-enhanced MR imaging examinations using 1.

T2-weighted MRI of the uterus: fast spin echo vs. breath-hold fast spin echo.

This study compared one routine T2-weighted fast spin echo (T2FSE) sequence with a breath-hold T2FSE (BH T2FSE) sequence of the female pelvis for image quality, uterine anatomy, lesion detection, and signal intensity measurements. Thirty-two consecutive women (mean age 41.7 years) were imaged at 1.

Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain.

Purpose: Supplemental, "as-needed," administration of an opioid is a common approach to the problem of breakthrough pain in cancer patients. Oral transmucosal fentanyl citrate (OTFC) is undergoing investigation as a new treatment for breakthrough pain. The primary purpose of the study was to demonstrate that a single-unit dose of OTFC can safely and effectively treat breakthrough pain.

Breakthrough pain in cancer patients: characteristics, prevalence, and treatment.

"Breakthrough pain" is a common clinical term that has not been conclusively defined or described. Breakthrough pain is a transitory flare of pain experienced when baseline pain has been reduced to a mild or moderate level. Breakthrough pain may be characterized by its relationship to a fixed around-the-clock (ATC) opioid dose, rapid onset and short duration, precipitating events, predictability, pathophysiology (with nociceptive pain being most easily controlled), and etiology.

Sequential use of ferumoxide particles and gadolinium chelate for the evaluation of focal liver lesions on MRI.

This study describes the sequential use of ferumoxide (superparamagnetic iron oxide) particles and nonspecific extracellular gadolinium chelate (Gd) for evaluation of focal liver lesions on MRI to evaluate order of contrast administration and imaging effect of the first contrast agent on sequences acquired after the second contrast agent. Thirteen patients underwent MR examinations that included ferumoxide and Gd. The order and timing of administration were as follows: separate sessions (three patients; Gd study 4-19 days before ferumoxide study), same session, Gd first (seven patients; Gd study 1-2 hours before ferumoxide study), and same session, ferumoxide first (three patients; ferumoxide administered less than 1 hour before Gd study).

Palliation of intractable cancer pain by MRI-guided cingulotomy.

Case Report: Three cases of intractable pain arising from widespread metastatic cancer with poor response to opioids were treated with MRI-guided cingulotomy.

Results And Conclusions: In most cases, MRI-guided cingulotomy was associated with significant pain relief and reduced opioid use. To provide insight into the role of MRI-guided cingulotomy in oncologic pain refractory to more conservative measures, the relative risks and benefits of cingulotomy are discussed, along with the course of one patient who experienced postoperative cognitive impairment.

Clinical realities and economic considerations: economics of intrathecal therapy.

The estimated annual cost of medical management of chronic back pain is $25 billion. Such management is often ineffective and overly costly. Most physicians who have employed intrathecal pain therapy attest to its efficacy in the management of intractable chronic pain.