Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique ...toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class.
Medline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR),χ2 tests and multivariable regression models were used to analyse for effect size and associations.
We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8–12.9), hypophysitis (OR 6.5, 95% CI 3.0–14.3) and rash (OR 2.0, 95% CI 1.8–2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (OR 6.4, 95% CI 3.2–12.7), hypothyroidism (OR 4.3, 95% CI 2.9–6.3), arthralgia (OR 3.5, 95% CI 2.6–4.8) and vitiligo (OR 3.5, 95% CI 2.3–5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573) showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis.
CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.
•The impact of nozzle density for 3D printed jet cooler is experimentally measured.•A numerical parameter sensitivity study is used to find optimal jet cooler design.•Constant cooling rate/pumping ...power requires different optimal design parameters.•Best design nozzle density is between 30 cm−2 and 300 cm−2 for constant flow rate.•Best design with highest nozzle density is for constant pumping power comparison.
Previous research studies showed that bare die liquid multi-jet impingement coolers with locally distributed outlets using silicon processing, mechanical micromachining, and additive manufacturing technology can achieve high cooling efficiency for high power electronic applications. The nozzle density is a crucial factor for thermal performance as well as for selecting the required fabrication technology. However, general design guidelines for the optimal nozzle density and cavity height are still missing in literature. In this paper, the impact of nozzle density on direct multi-jet impingement jet cooling is investigated using experiments and numerical modeling for an N×N nozzle array. The general scaling analysis with experimentally validated models is investigated based on three independent design parameters: nozzle density (N2/A), nozzle diameter (di) and cavity height (H). The objective is to find the optimal design parameters and to study the scaling trends. The experimental studies show that a very good thermal performance for the 8 × 8 jet array cooler with 1 × 1 mm2 cooling cells has be achieved as low as 0.13 cm2-K/W for a flow rate of 1000 ml/min. The best cooler design, expressed as the cooler with the highest COP value, can be achieved in the middle range of the nozzle density between 30 and 300nozzles per cm2 for the constant flow rate consideration. Comparisons in terms of constant cooler flow rate or constant pumping power will result in different optimal design parameter values.
This paper is to determine an initial value for a time-fractional diffusion-wave equation from the final time data. The regularity of the weak solution for the direct problem is improved. The ...existence and uniqueness of a weak solution for the adjoint problem are proved by using the Fourier method. The Tikhonov regularization method is applied for finding a stable approximate solution. In order to get the minimizer of the Tikhonov regularization functional, we propose a conjugate gradient algorithm based on the strict deductions of the sensitive problem and the adjoint problem. Four numerical examples in one-dimensional and two-dimensional cases are provided to show the effectiveness and stability of the proposed algorithm.
We work out theoretically a mechanism for magnetoelectric (ME) coupling driven by a buildup of an interfacial spiral spin density in ferromagnet (FM)/ferroelectric (FE) composites. We infer an ...intrinsic linear ME coupling that is most pronounced in the vicinity of the FM/FE interface acting within the spin-diffusion length lambdam of the order of nanometers. Our study delivers a strong coupling strength for Co(40 nm)/ BaTiO sub(3) that is in line with experiments. We identify a region of magnetic noncollinearity coupled to dielectric polarization that extends over lambdam around the interface, functionalizing the interface for electric control of magnetotransport and surface magnetic anisotropy.
Lower urinary tract symptoms affect more than half of older men. Options for bothersome symptoms include α-adrenergic-receptor blockers, 5α-reductase inhibitors, phosphodiesterase-5 inhibitor ...therapy, and antimuscarinic therapy.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.
Stage
A 59-year-old man with a history of benign prostatic hyperplasia and lower urinary tract symptoms comes for care. He has been receiving doxazosin at a dose of 4 mg daily (his only medication) for the past 2 years, with minimal improvement. He continues to have nocturia, a weak urinary stream, and urinary frequency (voiding eight times per day). How would you manage this case?
The Clinical Problem
Benign prostatic hyperplasia, a histologic diagnosis, is a condition that occurs with aging; the prevalence increases from 25% among men 40 to 49 years of age to more than 80% among men . . .
Immunotherapy and the role of imaging Carter, Brett W.; Bhosale, Priya R.; Yang, Wei T.
Cancer,
July 15, 2018, Letnik:
124, Številka:
14
Journal Article
We investigate the critical current I_{C} of ballistic Josephson junctions made of encapsulated graphene-boron-nitride heterostructures. We observe a crossover from the short to the long junction ...regimes as the length of the device increases. In long ballistic junctions, I_{C} is found to scale as ∝exp(-k_{B}T/δE). The extracted energies δE are independent of the carrier density and proportional to the level spacing of the ballistic cavity. As T→0 the critical current of a long (or short) junction saturates at a level determined by the product of δE (or Δ) and the number of the junction's transversal modes.
Since the introduction of serum prostate-specific antigen (PSA) screening 25 years ago, prostate cancer diagnosis and management have been guided by this biomarker. Yet, PSA has proven controversial ...as a screening assay owing to several inherent limitations. The next wave of prostate cancer biomarkers has emerged, introducing new assays in serum and urine that may supplement or, in time, replace PSA because of their higher cancer specificity. This expanding universe of biomarkers has been facilitated, in large part, by new genomic technologies that have enabled an unbiased look at cancer biology. Such efforts have produced several notable success stories that involve rapidly moving biomarkers from the bench to the clinic. However, biomarker research has centered on disease diagnostics, rather than prognosis and prediction, which would address disease management. The development of biomarkers to stratify risk of prostate cancer aggressiveness at the time of screening remains the greatest unmet clinical need in prostate cancer. We review the current state of prostate cancer biomarker research, including the PSA revolution, its impact on early cancer detection, the recent advances in biomarker discovery, and the future efforts that promise to improve clinical management of this disease.
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