189 research outputs found
Update on options for treatment of metastatic castration-resistant prostate cancer
Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA) testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC), the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16) in CRPC, several newer cytotoxic drugs (epothilones, satraplatin), targeted agents (abiraterone, MDV3100) and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cell
AIDS-Related Non-Hodgkin's Lymphoma in the Era of Highly Active Antiretroviral Therapy
In economically developed countries, AIDS-related lymphoma (ARL) accounts for a large proportion of malignances in HIV-infected individuals. Since the introduction of highly active anti-retroviral therapy (HAART) in 1996, epidemiology and prognosis of ARL have changed. While there is a slight increase in the incidence of Hodgkin's lymphoma in HIV-infected individuals, use of HAART has contributed to a decline in the incidence of non-Hodgkin's lymphoma (NHL) and also a decrease in the overall incidence of ARL. Strategies that employ HAART, improved supportive care, and the use of Rituximab with multi-agent chemotherapy have contributed to improved rates of complete remission and survival of patients with ARL that rival those seen in stage and histology matched HIV negative NHL patients. Most recent clinical trials demonstrate better outcomes with the use of rituximab in ARL. Tumor histogenesis (germinal center vs. non-germinal center origin) is associated with lymphoma-specific outcomes in the setting of AIDS-related diffuse-large B cell lymphoma. High-dose chemotherapy (HDCT) and autologous stem cell rescue (ASCT) can be effective for a subset of patients with relapsed ARL. HIV sero-status alone should not preclude consideration of ASCT in the setting of ARL relapse. Clinical trials investigating the role of allogeneic hematopoietic stem cell transplant in ARL are currently underway
SSI ANALYSIS OF TALL CHIMNEYS WITH ANNULAR RAFT CONSIDERING VARIABLE SOIL PROFILE
SSI analysis of a 200m reinforced concrete chimney with annular raft foundation under along-wind load is carried out in the present study. To study the effect of geometrical properties of chimney, different ratios of height to base diameter(slenderness ratio) are selected. The ratio of outer diameter to thickness of raft were also varied. To understand the effect of flexibility of soil, variable soil profile is considered below the foundation. Three different soil layers were considered below the foundation.Along-wind loads are calculated as per IS:4998-1992. Three dimensional analysis of chimney was carried out using ANSYS software. Lateral tip deflection in chimney and the settlement in raft were obtained in the analysis. The results show that the responses in chimney are affected by the flexibility of soil, slenderness ratio of chimney and thickness of raft
Formulation and Evaluation of Chitosan Based Hydrogel Matrix of Licorice for Targeting Helicobacter Pylori
In present investigation an attempt has been made to formulate and evaluate chitosan based
hydrogel of matrix of Licorice for targeting Helicobacter pylori.
Licorice was evaluated for its physical characteristics, analytical profiles and drug polymer
compatibility study. The prepared Hydrogel granules were evaluated for pre formulation
characteristics like Angle of repose, Bulk density, Tapped density and Carr’s index. The
results obtained were found to be satisfactory and within the specified limits.
A Stomach retentive licorice loaded chitosan hydrogel was prepared successfully by chemical
crosslinking method. Glutaraldehyde was used as chemical crosslinking agent.
After compression parameters like Thickness, Hardness, Weight variation, Friability, content
uniformity and In-Vitro release studies were evaluated.
Mucoadhesive study showed that, licorice loaded hydrogel have good mucoadhesion property
and retained in gastric environment tof stomach for prolonged period of time.
The results of In-vitro studies showed that by chitosan concentration the extent of swelling
and rate of drug release can be modulated.
In the present study the effect of concentration of polymer are studied through In-Vitro drug
release. It shows that increase in concentration of polymer leads to the controlled drug release
from hydrophilic chitosan hydrogelfor12 hrs, which means release rate from hydrophilic
chitosan hydrogel depends on type and concentration of polymer used in the formulation.
Hydrogel formulation (F5), containing chitosan and Crosslinking agent of Glutaraldehyde is
probably showing release upto 96.2±0.65% within 12 hrs.
The hydrogel prepared maintain drug concentration in stomach for prolonged period of time,
can be used as a drug delivery system for treatment of H. pylori infection and in management
of peptic ulcer.
According to stability study it was found that there was no significant change in average
weight, drug content and in vitro dissolution of optimized formulation (F5).
This can be expected to reduced the frequency of administration and decrease the dose
dependent side effects. The efficacy and safety of Licorice hydrogel dosage form are
expected to offer optimum therapeutic efficacy and improved patient compliance
Online Algorithms for Hierarchical Inference in Deep Learning applications at the Edge
We consider a resource-constrained Edge Device (ED), such as an IoT sensor or
a microcontroller unit, embedded with a small-size ML model (S-ML) for a
generic classification application and an Edge Server (ES) that hosts a
large-size ML model (L-ML). Since the inference accuracy of S-ML is lower than
that of the L-ML, offloading all the data samples to the ES results in high
inference accuracy, but it defeats the purpose of embedding S-ML on the ED and
deprives the benefits of reduced latency, bandwidth savings, and energy
efficiency of doing local inference. In order to get the best out of both
worlds, i.e., the benefits of doing inference on the ED and the benefits of
doing inference on ES, we explore the idea of Hierarchical Inference (HI),
wherein S-ML inference is only accepted when it is correct, otherwise the data
sample is offloaded for L-ML inference. However, the ideal implementation of HI
is infeasible as the correctness of the S-ML inference is not known to the ED.
We propose an online meta-learning framework that the ED can use to predict the
correctness of the S-ML inference. In particular, we propose to use the maximum
softmax value output by S-ML for a data sample and decide whether to offload it
or not. The resulting online learning problem turns out to be a Prediction with
Expert Advice (PEA) problem with continuous expert space. We propose two
different algorithms and prove sublinear regret bounds for them without any
assumption on the smoothness of the loss function. We evaluate and benchmark
the performance of the proposed algorithms for image classification application
using four datasets, namely, Imagenette and Imagewoof, MNIST, and CIFAR-10.Comment: The original version was submitted to a journal and was later
revised. The updated version was accepted in a journal and will be published
soon. The 'Journal reference' will be updated as and when the information is
availabl
All-Trans Retinoic Acid-Induced Pseudotumor Cerebri during Induction Therapy for Acute Promyelocytic Leukemia: A Case Report and Literature Review
All-trans retinoic acid (ATRA), a derivative of vitamin A, is an essential component in the treatment of acute promyelocytic leukemia (APL). Though considered to be a relatively safe drug, use of ATRA can lead to several side effects such as retinoic acid syndrome and pseudotumor cerebri (PC). PC is a rare disorder characterized by neurologic and ocular signs and symptoms of increased intracranial pressure, but with normal cerebrospinal fluid composition and normal brain imaging. Most of the previous studies suggest that PC, as a complication of ATRA therapy, occurs predominantly in the pediatric age group. Herein, we report a rare case of ATRA-induced PC in a 38-year-old woman undergoing induction treatment for APL. Symptoms improved with discontinuation of ATRA and treatment with acetazolamide. Concomitant administration of medications such as triazole antifungals which influence the cytochrome P-450 system can exacerbate this potential complication of ATRA. In this paper, we also review the current literature, provide a descriptive analysis of clinical features, and discuss the principles of management of ATRA-induced PC
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