Advances in photonics and nanotechnology have the potential to revolutionize humanity's ability to communicate and compute. To pursue these advances, it is mandatory to understand and properly model ...interactions of light with materials such as silicon and gold at the nanoscale, i.e., the span of a few tens of atoms laid side by side. These interactions are governed by the fundamental Maxwell's equations of classical electrodynamics, supplemented by quantum electrodynamics.This book presents the current state-of-the-art in formulating and implementing computational models of these interactions. Maxwell's equations are solved using the finite-difference time-domain (FDTD) technique, pioneered by the senior editor, whose prior Artech House books in this area are among the top ten most-cited in the history of engineering. You discover the most important advances in all areas of FDTD and PSTD computational modeling of electromagnetic wave interactions.This cutting-edge resource helps you understand the latest developments in computational modeling of nanoscale optical microscopy and microchip lithography. You also explore cutting-edge details in modeling nanoscale plasmonics, including nonlocal dielectric functions, molecular interactions, and multi-level semiconductor gain. Other critical topics include nanoscale biophotonics, especially for detecting early-stage cancers, and quantum vacuum, including the Casimir effect and blackbody radiation.
Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more ...complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms.
Advances in our understanding of tumor biology now permit greater personalization of radiotherapy for early-stage breast cancer. De-escalation of radiotherapy is an important opportunity that exists ...due to improvements in breast imaging, surgery, pathology, and systemic therapy. These modern tools, in addition to molecular subtype and prediction assays, have allowed us to select certain patients with breast cancer based on favorable biology who are at sufficiently low-risk of local recurrence that they may reasonably consider the omission of radiotherapy to reduce toxicity and burden. For decades, clinical trials have been conducted to try to identify the population of patients in whom the risk of recurrence in the absence of radiotherapy is sufficiently small that omission of adjuvant radiotherapy might acceptably be considered after breast conserving surgery. Trials to date have largely included patients with estrogen receptor-positive breast cancer selected based upon clinicopathologic characteristics alone and have yet to identify a patient population for whom radiotherapy is not effective. They have, however, identified women with lower absolute risks of locoregional recurrence with radiotherapy omission, and current guidelines do recognize this patient population as candidates for radiotherapy omission after breast conserving surgery. Studies that assess not just clinicopathologic features but predictive molecular biomarkers of the underlying biology are currently ongoing. This manuscript will briefly review historical trials evaluating the role of radiotherapy after breast conserving surgery as well as discuss the exciting ongoing trials in hormone receptor-positive disease leveraging our growing appreciation of tumor biology and molecular prediction to identify a population of patients who may reasonably consider omitting radiotherapy after breast conserving surgery.
Tumor cell migration toward and intravasation into capillaries is an early and key event in cancer metastasis, yet not all cancer cells are imbued with the same capability to do so. This ...heterogeneity within a tumor is a fundamental property of cancer. Tools to help us understand what molecular characteristics allow a certain subpopulation of cells to spread from the primary tumor are thus critical for overcoming metastasis. Conventional in vitro migration platforms treat populations in aggregate, which leads to a masking of intrinsic differences among cells. Some migration assays reported recently have single-cell resolution, but these platforms do not provide for selective retrieval of the distinct migrating and non-migrating cell populations for further analysis. Thus, to study the intrinsic differences in cells responsible for chemotactic heterogeneity, we developed a single-cell migration platform so that individual cells' migration behavior can be studied and the heterogeneous population sorted based upon chemotactic phenotype. Furthermore, after migration, the highly chemotactic and non-chemotactic cells were retrieved and proved viable for later molecular analysis of their differences. Moreover, we modified the migration channel to resemble lymphatic capillaries to better understand how certain cancer cells are able to move through geometrically confining spaces.
Many resident physicians struggle with effective interprofessional collaboration (IPC), but characterization of their challenges is not well known. This study examines gaps in IPC skills for ...graduating medical students entering residency. A needs assessment was completed to evaluate factors that impact resident physicians' ability to effectively collaborate with other healthcare professionals. This study included online surveys of 123 recent medical school graduates, 21 semi-structured interviews of residency program directors, and 3 focus groups of healthcare professionals who interacted with residents. Survey results were analyzed for means and narratives from surveys, interviews, and focus groups were analyzed for themes. We found that graduates felt they did not have a strong understanding of other providers' roles and did not feel well prepared to handle conflict with other providers or navigate interprofessional team dynamics. Themes emerging from narrative data generally aligned with the Interprofessional Education Collaborative core competencies including understanding team roles, communicating effectively, and working effectively in a team, but these interviews also elucidated an additional theme, overcoming system barriers. Data from this work can inform curricula in preparation for the transition to residency. The authors also offer an educational framework for learning effective IPC as a new team member.
Comparative efficacy research performed using population registries can be subject to significant bias. There is an absence of objective data demonstrating factors that can sufficiently reduce bias ...and provide accurate results.
MEDLINE was searched from January 2000 to October 2016 for observational studies comparing two treatment regimens for any diagnosis of cancer, using SEER, SEER-Medicare, or the National Cancer Database. Reporting quality and statistical methods were assessed using components of the STROBE criteria. Randomized trials comparing the same treatment regimens were identified. Primary outcome was correlation between survival hazard ratio (HR) estimates provided by the observational studies and randomized trials. Secondary outcomes included agreement between matched pairs and predictors of agreement.
Of 3,657 studies reviewed, 350 treatment comparisons met eligibility criteria and were matched to 121 randomized trials. There was no significant correlation between the HR estimates reported by observational studies and randomized trials (concordance correlation coefficient, 0.083; 95% CI, -0.068 to 0.230). Forty percent of matched studies were in agreement regarding treatment effects (κ, 0.037; 95% CI, -0.027 to 0.1), and 62% of the observational study HRs fell within the 95% CIs of the randomized trials. Cancer type, data source, reporting quality, adjustment for age, stage, or comorbidities, use of propensity weighting, instrumental variable or sensitivity analysis, and well-matched study population did not predict agreement.
We were unable to identify any modifiable factor present in population-based observational studies that improved agreement with randomized trials. There was no agreement beyond what is expected by chance, regardless of reporting quality or statistical rigor of the observational study. Future work is needed to identify reliable methods for conducting population-based comparative efficacy research.
Hyponatremia is the most common electrolyte abnormality in hospitalized patients. When symptomatic (hyponatremic encephalopathy), the overall morbidity is 34%. Individuals most susceptible to death ...or permanent brain damage are prepubescent children and menstruant women. Failure of the brain to adapt to the hyponatremia leads to brain damage. Major factors that can impair brain adaptation include hypoxia and peptide hormones. In children, physical factors--discrepancy between skull size and brain size--are important in the genesis of brain damage. In adults, certain hormones--estrogen and vasopressin (usually elevated in cases of hyponatremia)--have been shown to impair brain adaptation, decreasing both cerebral blood flow and oxygen utilization. Initially, hyponatremia leads to an influx of water into the brain, primarily through glial cells and largely via the water channel aquaporin (AQP)4. Water is thus shunted into astrocytes, which swell, largely preserving neuronal cell volume. The initial brain response to swelling is adaptation, utilizing the Na(+)-K(+)-ATPase system to extrude cellular Na(+). In menstruant women, estrogen + vasopressin inhibits the Na(+)-K(+)-ATPase system and decreases cerebral oxygen utilization, impairing brain adaptation. Cerebral edema compresses the respiratory centers and also forces blood out of the brain, both lowering arterial Po(2) and decreasing oxygen utilization. The hypoxemia further impairs brain adaptation. Hyponatremic encephalopathy leads to brain damage when brain adaptation is impaired and is a consequence of both cerebral hypoxia and peptide hormones.
Sodium has long been considered an alternative active battery cation to lithium because of the chemical similarity and the overwhelming natural abundance of Na compared to Li. In the “early days” of ...poly (ethylene oxide) (PEO) and alkali metal salt complexes proposed as polymer electrolytes, studies of Na-salt/PEO materials were nearly as prevalent as those of lithium analogues. Fast forwarding to the present day, there is growing interest in sodium battery chemistry spurred by the challenges of continued advancement in lithium-based batteries. This article reviews the progress made in sodium-based polymer electrolytes from the early days of PEO to the present time. Other polymeric electrolytes such as gel polymer electrolytes (GPE), including formulations based on ionic liquids (ILs), are also discussed.
The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined.
To determine the effects of immediate vs ...gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure.
A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017.
(1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes.
Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.
Among 1250 randomized participants (mean age, 45 years; 549 women 44%; 958 77% completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million ppm 95% CI, -4.89 to -3.23; P < .0055), 3-HPMA (ratio of geometric means, 0.83 95% CI, 0.77 to 0.88; P < .0055), and PheT (ratio of geometric means, 0.88 95% CI, 0.83 to 0.93; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 95% CI, -4.40 to -2.36; P < .0055), 3-HPMA (ratio of geometric means, 0.81 95% CI, 0.75 to 0.88; P < .0055), and PheT (ratio of geometric means, 0.86 95% CI, 0.81 to 0.92; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 95% CI, -0.31 to 1.67; P = .18), 3-HPMA (ratio of geometric means, 0.98 95% CI, 0.91 to 1.06; P = .64), and PheT (ratio of geometric means, 0.98 95% CI, 0.92 to 1.04; P = .52).
Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control.
clinicaltrials.gov Identifier: NCT02139930.
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