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Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Mariella G Filbin, Dominik Sturm
Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features...
February 2018: Seminars in Neurology
Elizabeth R Gerstner, Kristian W Pajtler
Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades...
February 2018: Seminars in Neurology
Anna S Berghoff, Priscilla K Brastianos
Brain metastases (BMs) reflect an area of high clinical need, as up to 40% of patients with metastatic cancer will develop this morbid and highly fatal complication. Historically, treatment strategies have relied on local approaches including radiosurgery, whole-brain radiotherapy, and neurosurgical resection. Recently, targeted and immune-modulating therapies have shown promising responses and have been introduced in the clinical management of patients with BMs. Recent improvements in genomic technologies have enriched our understanding of BMs and have demonstrated that BMs present with significant genetic divergence from the originating primary tumor, such that potentially targetable genetic alterations are detected only in the BMs...
February 2018: Seminars in Neurology
Sarah Löw, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma limited to the brain, spinal cord, leptomeninges, and eyes. The majority of patients are immunocompetent, with a median age of 65 years at diagnosis. Historically, whole-brain radiation therapy (WBRT) was the first and sole treatment for PCNSL. Today, due to the recognized neurotoxicity of WBRT, this modality is usually avoided in the treatment. Most chemotherapy regimens are based on high-dose methotrexate plus the anti-CD20 monoclonal antibody rituximab, leading to high response rates, but 5-year survival is still poor at approximately 30% compared with other extranodal lymphomas...
February 2018: Seminars in Neurology
Scott R Plotkin, Antje Wick
Neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis are a group of related classically inherited but often times sporadic tumor suppressor syndromes. Neuro-oncologists should recognize these syndromes, initiate necessary tests in patients with a clinical suspicion, and support genetic counseling of patients and families. In this review, clinical presentation, diagnostic criteria, day-to-day management including supportive care as well as updates on genetics, and experimental treatment strategies are discussed...
February 2018: Seminars in Neurology
Michael Platten, David A Reardon
Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined...
February 2018: Seminars in Neurology
Darshan Khangura, L Romayne Kurukulasuriya, Adam Whaley-Connell, James R Sowers
The presence of hypertension in individuals with type 2 diabetes augments the risk for cardiovascular morbidity and mortality. In this regard, data support that management of hypertension in this high-risk population is a critical risk reduction strategy. In recent years, a number of work groups have redefined hypertension, management strategies, and targets. In this context, there is still considerable discussion on an appropriate target for blood pressure in the diabetic population. However, despite this discussion on target blood pressure, it is widely recognized that there is considerable residual risk for heightened cardiovascular events in the hypertensive, diabetic population despite widespread awareness and treatment...
March 14, 2018: American Journal of Hypertension
Marco Armando, Corrado Sandini, Maelle Chambaz, Marie Schaer, Maude Schneider, Stephan Eliez
Converging evidence suggests that psychosis emerges from the complex interaction of genetic and environmental factors. Stressful life events (SLEs) play a prominent role in combination with coping strategies and with a dysfunctional hypothalamus-pituitary-adrenal axis (HPAA). It has been proposed that the framework of schizotypy might help disentangle the interaction between genetic and environmental factors in the pathogenesis of psychosis. Similarly, 22q11.2 deletion syndrome (22q11DS) is considered as a genetic model of psychosis vulnerability...
March 14, 2018: Schizophrenia Bulletin
Kaitlin C Maguire, Douglas J Shinneman, Kevin M Potter, Valerie D Hipkins
Unique responses to climate change can occur across intraspecific levels, resulting in individualistic adaptation or movement patterns among populations within a given species. Thus, the need to model potential responses among genetically distinct populations within a species is increasingly recognized. However, predictive models of future distributions are regularly fit at the species level, often because intraspecific variation is unknown or is identified only within limited sample locations. In this study, we considered the role of intraspecific variation to shape the geographic distribution of ponderosa pine (Pinus ponderosa), an ecologically and economically important tree species in North America...
March 14, 2018: Systematic Biology
A Hillary Steinhart
No abstract text is available yet for this article.
March 14, 2018: Inflammatory Bowel Diseases
Farnaz Foolad, Brandie D Taylor, Samuel A Shelburne, Cesar A Arias, Samuel L Aitken
VRE are associated with ∼1300 deaths per year in the USA. Recent literature suggests that daptomycin, a cyclic lipopeptide antibiotic with concentration-dependent bactericidal activity, is the preferred treatment option for VRE bacteraemia, yet the optimal dosing strategy for this indication has not been established. In vitro evidence suggests that higher-than-labelled doses of daptomycin are required to optimally treat VRE bacteraemia and to inhibit the development of resistance. However, concern of dose-dependent toxicities, notably increases in creatine phosphokinase and the development of rhabdomyolysis, are a barrier to initiating high-dose schemes in clinical practice...
March 13, 2018: Journal of Antimicrobial Chemotherapy
Matthew A Psioda, Joseph G Ibrahim
We consider the problem of Bayesian sample size determination for a clinical trial in the presence of historical data that inform the treatment effect. Our broadly applicable, simulation-based methodology provides a framework for calibrating the informativeness of a prior while simultaneously identifying the minimum sample size required for a new trial such that the overall design has appropriate power to detect a non-null treatment effect and reasonable type I error control. We develop a comprehensive strategy for eliciting null and alternative sampling prior distributions which are used to define Bayesian generalizations of the traditional notions of type I error control and power...
March 14, 2018: Biostatistics
Dayna A Johnson, Jana A Hirsch, Kari A Moore, Susan Redline, Ana V Diez Roux
Although dense neighborhood built environments support increased physical activity and lower obesity, these features may also disturb sleep. Therefore, we sought to understand the association between the built environment and objectively measured sleep. From 2010 to 2013, we analyzed data from examination 5 of the Multi-Ethnic Study of Atherosclerosis, a diverse population from 6 US cities. We fit multilevel models that assessed the association between the built environment (Street Smart Walk Score, social engagement destinations, street intersections, and population density) and sleep duration or efficiency from 1-week wrist actigraphy in 1,889 individuals...
March 14, 2018: American Journal of Epidemiology
Clément Niel, Christine Sinoquet, Christian Dina, Ghislain Rocheleau
Motivation: Large scale genome-wide association studies (GWAS) are tools of choice for discovering associations between genotypes and phenotypes. To date, many studies rely on univariate statistical tests for association between the phenotype and each assayed single nucleotide polymorphism (SNP). However, interaction between SNPs, namely epistasis, must be considered when tackling the complexity of underlying biological mechanisms. Epistasis analysis at large scale entails a prohibitive computational burden when addressing the detection of more than two interacting SNPs...
March 14, 2018: Bioinformatics
Rada M Savic, Prasanna Jagannathan, Richard Kajubi, Liusheng Huang, Nan Zhang, Moses Were, Abel Kakuru, Mary K Muhindo, Norah Mwebaza, Erika Wallender, Tamara D Clark, Bishop Opira, Moses Kamya, Diane V Havlir, Philip J Rosenthal, Grant Dorsey, Francesca T Aweeka
Background: Dihydroartemsinin-piperaquine is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies. Methods: HIV-uninfected pregnant women were enrolled in a placebo-controlled trial of IPTp at 12-20 weeks gestation and randomized to: sulfadoxine-pyrimethamine every 8 weeks (n=106), dihydroartemsinin-piperaquine every 8 weeks (n=94), or dihydroartemsinin-piperaquine every 4 weeks (n=100) during pregnancy...
March 14, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Suzanne Grant, Bruce Guthrie
Patient safety is an increasing concern for health systems internationally. The majority of administrative work in UK general practice takes place in the context of organisational routines such as repeat prescribing and test results handling, where high workloads and increased clinician dependency on administrative staff have been identified as an emerging safety issue. Despite this trend, most research to date has focused on the redistribution of the clinical workload between doctors, nurses and allied health professionals within individual care settings...
March 2, 2018: Social Science & Medicine
Zhen-Zhen Cao, Mei-Ling Qin, Xiao-Yan Lin, Zhi-Wei Zhu, Ming-Xue Chen
Sulfur (S) fertilizer application in rice (Oryza sativa L.) is crucial in determining rice grain productivity and quality. However, little information is available concerning the effect of S supply on cadmium (Cd) uptake and translocation in rice. In this study, both hydroponic and soil experiments were conducted to investigate the influence of S supply on Cd accumulation in rice under two Cd levels (0 and 50 μM), combined with three S concentrations (0, 2.64 and 5.28 mM). The moderate and excessive S supply (2...
March 13, 2018: Environmental Pollution
Mahfuza Mubarak, Hyokyung Jeon, Md Shahinul Islam, Cheolho Yoon, Jong-Seong Bae, Seong-Ju Hwang, Won San Choi, Ha-Jin Lee
Herein, Mg/Fe layered double hydroxide (MF-LDH) hollow nanospheres were successfully prepared by a one-step thermal method. After the thermal treatment of MF-LDH nanospheres at 400 °C, the MF-LDH was converted into the corresponding oxide, Mg/Fe layered double oxide (MF-LDO), which maintained the hollow nanosphere structure. The MF-LDO hollow nanospheres exhibited excellent adsorption efficiency for both As(V) and Cr(VI), showing 99% removal within 5 min and providing maximum removal capacities of 178...
March 6, 2018: Chemosphere
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
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