A novel indole derivative, 2-{3-[1-(benzylsulfonyl)piperidin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone, suppresses hedgehog signaling and drug-resistant tumor growth.

The Hedgehog (Hh) signaling pathway plays important roles in various physiological functions. Several malignancies, such as basal cell carcinoma (BCC) and medulloblastoma (MB), have been linked to the aberrant activation of Hh signaling. Although therapeutic drugs have been developed to inhibit Hh pathway-dependent cancer growth, drug resistance remains a major obstacle in cancer treatment. Here, we show that the newly identified, 2-{3-[1-(benzylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone analog (LKD1214) exhibits comparable potency to vismodegib in suppressing the Hh pathway activation. LKD1214 represses Smoothened (SMO) activity by blocking its ciliary translocation. Interestingly, we also identified that it has a distinctive binding interface with SMO compared with other SMO-regulating chemicals. Notably, it maintains an inhibitory activity against the SmoD477H mutant, as observed in a patient with vismodegib-resistant BCC. Furthermore, LKD1214 inhibits tumor growth in the mouse model of MB. Collectively, these findings suggest that LKD1214 has the therapeutic potential to overcome drug-resistance in Hh-dependent cancers.

Effect of multiple quantum well periods on structural properties and performance of extended short-wavelength infrared LEDs.

We present research on the role of multiple quantum well periods in extended short-wavelength infrared InGaAs/InAsPSb type-I LEDs. The fabricated LEDs consisted of 6, 15, and 30 quantum well periods, and we evaluated the structural properties and device performance through a combination of theoretical simulations and experimental characterization. The strain and energy band offset was precisely controlled by carefully adjusting the composition of the InAsPSb quaternary material, achieving high valence and conduction band offsets of 350 meV and 94 meV, respectively. Our LEDs demonstrated a high degree of relaxation of 94-96 %. Additionally, we discovered that the temperature-dependent dark current characterization attributed to generation-recombination and trap-assign tunneling, with trap-assign tunneling being more dominant at lower current injections. Electroluminescence analysis revealed that the predominant emission mechanism of the LEDs originated from localized exciton and free exciton radiative recombination, which the 30 quantum wells LED exhibited the highest contribution of the localized exciton/free exciton radiative recombination. We observed that increasing the quantum well periods from 6 to 15 led to an increase in the 300 K electroluminescence intensity of the LED. However, extending the quantum well period to 30 resulted in a decline in emission intensity due to the degradation of the epitaxial film quality.

Improving infra-red polarized imaging efficiency in a bilayer wire-grid polarizer.

The optical, plasmonic, and imaging performance of an infra-red polarized system exceeds that of a conventional infra-red detector due to its high resolution and precision. The wire-grid polarizer has large potential for use in an infra-red polarized imaging device owing to its large polarization efficiency. In this study, we theoretically and experimentally investigate a method to improve the polarization efficiency of a wire-grid polarizer. Here, we demonstrated a high-performance wire grid polarizer with a maximum extinction ratio (ER) of 355 using a bilayer structure and dielectric material in the mid-wavelength infra-red (MWIR) region (3000 nm-5000 nm), which is a 4 times higher ER value than that of the monolayer structure. More interestingly, we were able to improve the performance of the bilayer wire-grid polarizer by devising a method to improve the surface roughness using Ar ion milling. The ER for the after-milled sample was 1255, which was markedly larger than that of the before-milled sample. The results of transmittance measurement confirmed that the improvement in the ER was due to the Fabry-Perot (F-P) phenomenon caused by constructive or destructive interference in the bilayer wire-grid structure and the enhancement of the surface smoothness. These results will help design a polarizer structure that will maximize the polarization efficiency and realize a high-performance infrared polarized imaging system.

Polarization-Sensitive and Wide Incidence Angle-Insensitive Fabry-Perot Optical Cavity Bounded by Two Metal Grating Layers.

Infrared (IR) polarimetric imaging has attracted attention as a promising technology in many fields. Generally, superpixels consisting of linear polarizer elements at different angles plus IR imaging array are used to obtain the polarized target signature by using the detected polarization-sensitive intensities. However, the spatial arrangement of superpixels across the imaging array may lead to an incorrect polarimetric signature of a target, due to the range of angles from which the incident radiation can be collected by the detector. In this article, we demonstrate the effect of the incident angle on the polarization performance of an alternative structure where a dielectric layer is inserted between the nanoimprinted subwavelength grating layers. The well-designed spacer creates the Fabry-Perot cavity resonance, and thereby, the intensity of transverse-magnetic I-polarized light transmitted through two metal grating layers is increased as compared with a single-layer metal grating, whereas transverse-electric (TE)-transmitted light intensity is decreased. TM-transmittance and polarization extinction ratio (PER) of normally incident light of wavelength 4.5 µm are obtained with 0.49 and 132, respectively, as the performance of the stacked subwavelength gratings. The relative change of the PERs for nanoimprint-lithographically fabricated double-layer grating samples that are less than 6% at an angle of incidence up to 25°, as compared to the normal incidence. Our work can pave the way for practical and efficient polarization-sensitive elements, which are useful for many IR polarimetric imaging applications.

Plasmonic-Layered InAs/InGaAs Quantum-Dots-in-a-Well Pixel Detector for Spectral-Shaping and Photocurrent Enhancement.

The algorithmic spectrometry as an alternative to traditional approaches has the potential to become the next generation of infrared (IR) spectral sensing technology, which is free of physical optical filters, and only a very small number of data are required from the IR detector. A key requirement is that the detector spectral responses must be engineered to create an optimal basis that efficiently synthesizes spectral information. Light manipulation through metal perforated with a two-dimensional square array of subwavelength holes provides remarkable opportunities to harness the detector response in a way that is incorporated into the detector. Instead of previous experimental efforts mainly focusing on the change over the resonance wavelength by tuning the geometrical parameters of the plasmonic layer, we experimentally and numerically demonstrate the capability for the control over the shape of bias-tunable response spectra using a fixed plasmonic structure as well as the detector sensitivity improvement, which is enabled by the anisotropic dielectric constants of the quantum dots-in-a-well (DWELL) absorber and the presence of electric field along the growth direction. Our work will pave the way for the development of an intelligent IR detector, which is capable of direct viewing of spectral information without utilizing any intervening the spectral filters.

Deterministic Nanoassembly of Quasi-Three-Dimensional Plasmonic Nanoarrays with Arbitrary Substrate Materials and Structures.

Guided manipulation of light through periodic nanoarrays of three-dimensional (3D) metal-dielectric patterns provides remarkable opportunities to harness light in a way that cannot be obtained with conventional optics yet its practical implementation remains hindered by a lack of effective methodology. Here we report a novel 3D nanoassembly method that enables deterministic integration of quasi-3D plasmonic nanoarrays with a foreign substrate composed of arbitrary materials and structures. This method is versatile to arrange a variety of types of metal-dielectric composite nanoarrays in lateral and vertical configurations, providing a route to generate heterogeneous material compositions, complex device layouts, and tailored functionalities. Experimental, computational, and theoretical studies reveal the essential design features of this approach and, taken together with implementation of automated equipment, provide a technical guidance for large-scale manufacturability. Pilot assembly of specifically engineered quasi-3D plasmonic nanoarrays with a model hybrid pixel detector for deterministic enhancement of the detection performances demonstrates the utility of this method.

Association of Inadequate Caloric Supplementation with 30-Day Mortality in Critically Ill Postoperative Patients with High Modified NUTRIC Score.

Modified NUTRIC (mNUTRIC) score is a useful assessment tool to determine the risk of malnutrition in patients on mechanical ventilation (MV). We identified associations between postoperative calorie adequacy, 30-day mortality, and surgical outcomes in patients with high mNUTRIC scores. Medical records of 272 patients in the intensive care unit who required MV support for >24 h after emergency gastro-intestinal (GI) surgery between January 2007 and December 2017 were reviewed. Calorie adequacy in percentage (Calorie intake in 5 days ÷ Calorie requirement for 5 days × 100) was assessed in patients with high (5⁻9) and low (0⁻4) mNUTRIC scores. In the high mNUTRIC score group, patients with inadequate calorie supplementation (calorie adequacy <70%) had higher 30-day mortality than those with adequate supplementation (31.5% vs. 11.1%; p = 0.010); this was not observed in patients with low mNUTRIC scores. This result was also confirmed through Kaplan⁻Meier survival curve (p = 0.022). Inadequate calorie supplementation in the high mNUTRIC score group was not associated with Intra-abdominal infection (p = 1.000), pulmonary complication (p = 0.695), wound complication (p = 0.407), postoperative leakage (p = 1.000), or infections (p = 0.847). Inadequate calorie supplementation after GI surgery was associated with higher 30-day mortality in patients with high mNUTRIC scores. Therefore, adequate calorie supplementation could contribute to improved survival of critically ill postoperative patients with high risk of malnutrition.

Addition of lactic acid levels improves the accuracy of quick sequential organ failure assessment in predicting mortality in surgical patients with complicated intra-abdominal infections: a retrospective study.

Background: The quick sequential organ failure assessment (qSOFA) alone has a poor sensitivity for predicting mortality in patients with complicated intra-abdominal infections, and plasma lactate levels have been shown to have a strong association with mortality in critically ill patients. Therefore, this study aimed to compare the performance of qSOFA with a score derived from a combination of qSOFA and serum lactate levels for predicting mortality in surgical patients with complicated intra-abdominal infections. Methods: This retrospective study was performed at a university hospital. The medical records of 457 patients who presented to the emergency department (ED) between January 2008 and December 2016 and required emergency gastrointestinal surgery for a complicated intra-abdominal infection were reviewed retrospectively. qSOFA criteria, sequential organ failure assessment (SOFA) scores, and plasma lactate levels during their ED stay were collected. We performed area under receiver operating characteristic (AUROC) curve and sensitivity analysis to compare the performance of qSOFA alone with that of a score derived from the use of a combination of the qSOFA and lactate levels for predicting patient mortality. Results: Fifty patients (10.9%) died during hospitalization. The combined qSOFA and lactate level score was superior to qSOFA alone (AUROC = 0.754 vs. 0.717, p = 0.039, respectively) and comparable to the full SOFA score (AUROC = 0.754 vs. 0.795, p = 0.127, respectively) in predicting mortality. Sensitivity and specificity of qSOFA alone were 46 and 86%, respectively, and those of the combined score were 72 and 73%, respectively (p < 0.001). Conclusion: A score derived from the qSOFA and serum lactate levels had better predictive performance with higher sensitivity than the qSOFA alone in predicting mortality in patients with complicated intra-abdominal infections and had a comparable predictive performance to that of the full SOFA score.

A Low-loss Metasurface Antireflection Coating on Dispersive Surface Plasmon Structure.

Over the years, there has been increasing interest in the integration of metal hole array (MHA) with optoelectronic devices, as a result of enhanced coupling of incident light into the active layer of devices via surface plasmon polariton (SPP) resonances. However, not all incident light contributes to the SPP resonances due to significant reflection loss at the interface between incident medium and MHA. Conventional thin-film antireflection (AR) coating typically does not work well due to non-existing material satisfying the AR condition with strong dispersion of MHA's effective impedances. We demonstrate a single-layer metasurface AR coating that completely eliminates the refection and significantly increases the transmission at the SPP resonances. Operating at off-resonance wavelengths, the metasurface exhibits extremely low loss and does not show resonant coupling with the MHA layer. The SPP resonance wavelengths of MHA layer are unaffected whereas the surface wave is significantly increased, thereby paving the way for improved performance of optoelectronic devices. With an improved retrieval method, the metasurface is proved to exhibit a high effective permittivity () and extremely low loss (tan δ ~ 0.005). A classical thin-film AR coating mechanism is identified through analytical derivations and numerical simulations.

Experimental Demonstration of Adaptive Infrared Multispectral Imaging using Plasmonic Filter Array.

In our previous theoretical study, we performed target detection using a plasmonic sensor array incorporating the data-processing technique termed "algorithmic spectrometry". We achieved the reconstruction of a target spectrum by extracting intensity at multiple wavelengths with high resolution from the image data obtained from the plasmonic array. The ultimate goal is to develop a full-scale focal plane array with a plasmonic opto-coupler in order to move towards the next generation of versatile infrared cameras. To this end, and as an intermediate step, this paper reports the experimental demonstration of adaptive multispectral imagery using fabricated plasmonic spectral filter arrays and proposed target detection scenarios. Each plasmonic filter was designed using periodic circular holes perforated through a gold layer, and an enhanced target detection strategy was proposed to refine the original spectrometry concept for spatial and spectral computation of the data measured from the plasmonic array. Both the spectrum of blackbody radiation and a metal ring object at multiple wavelengths were successfully reconstructed using the weighted superposition of plasmonic output images as specified in the proposed detection strategy. In addition, plasmonic filter arrays were theoretically tested on a target at extremely high temperature as a challenging scenario for the detection scheme.

Hospitalized patients' understanding of their plan of care.

OBJECTIVE: To evaluate hospitalized patients' understanding of their plan of care. PATIENTS AND METHODS: Interviews of a cross-sectional sample of hospitalized patients and their physicians were conducted from June 6 through June 26, 2008. Patients were asked whether they knew the name of the physician and nurse responsible for their care and specific questions about 6 aspects of the plan of care for the day (primary diagnosis, planned tests, planned procedures, medication changes, physician services consulted, and the expected length of stay). Physicians were interviewed and asked about the plan of care in the same fashion as for the patients. Two board-certified internists reviewed responses and rated patient-physician agreement on each aspect of the plan of care as none, partial, or complete agreement. RESULTS: Of 250 eligible patients, 241 (96%) agreed to be interviewed. A total of 233 (97%) of 241 physicians completed the interview, although sample sizes vary because of missing data elements. Of 239 patients, 77 (32%) correctly named at least 1 of their hospital physicians, and 143 patients (60%) correctly named their nurses. For each aspect of care, patients and physicians lacked agreement on the plan of care in a large number of instances. Specifically, there was no agreement between patients and physicians on planned tests or procedures for the day in 87 (38%) of 231 [corrected] instances and in 22 (10%) of 231 [corrected] instances. Complete agreement on the anticipated length of stay occurred in only 85 (39%) of 218 instances. CONCLUSION: A substantial portion of hospitalized patients do not understand their plan of care. Patients' limited understanding of their plan of care may adversely affect their ability to provide informed consent for hospital treatments and to assume their own care after discharge.

Impact of localizing physicians to hospital units on nurse-physician communication and agreement on the plan of care.

BACKGROUND: A significant barrier to communication among patient care providers in hospitals is the geographic dispersion of team members. OBJECTIVE: To determine whether localizing physicians to specific patient care units improves nurse-physician communication and agreement on patients' plans of care. METHODS: We conducted structured interviews of a cross-sectional sample of nurses and physicians before and after an intervention to localize physicians to specific patient care units. Interviews characterized patterns of nurse-physician communication and assessed understanding of patients' plans of care. Two internists reviewed responses and rated nurse-physician agreement on six aspects of the plan of care as none, partial, or complete agreement. RESULTS: Three hundred eleven of 342 (91%) and 291 of 294 (99%) patients' nurses and 301 of 342 (88%) and 285 of 294 (97%) physicians completed the interview during the pre- and post-localization periods. Two hundred nine of 285 (73%) patients were localized to physicians' designated patient care units in the post-localization period. After localization, a higher percentage of patients' nurses and physicians was able to correctly identify one another (93% vs. 71%; p < 0.001 and 58% vs. 36%; p < 0.001, respectively). Nurses and physicians reported more frequent communication after localization (68% vs. 50%; p < 0.001 and 74% vs. 61%; p < 0.001, respectively). Nurse-physician agreement was significantly improved for two aspects of the plan of care: planned tests and anticipated length of stay. CONCLUSIONS: Although nurses and physicians were able to identify one another and communicated more frequently after localizing physicians to specific patient care units, there was little impact on nurse-physician agreement on the plan of care.

Knowledge and awareness of congenital cytomegalovirus among women.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. METHODS: Women were surveyed about newborn infections at 7 different geographic locations. RESULTS: Of the 643 women surveyed, 142 (22%) had heard of congenital CMV. Awareness increased with increasing levels of education (P<.0001). Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus 16%, P <.0001). Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%), but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. CONCLUSION: Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies.

Fetal heart rate reactivity differs by women's psychiatric status: an early marker for developmental risk?

OBJECTIVE: To determine whether there are differences in fetal heart rate (FHR) reactivity associated with women's psychiatric status. METHOD: In 57 women in their 36th to 38th week of pregnancy (mean age 27 +/- 6 years), electrocardiogram, blood pressure (BP), respiration (RSP), and FHR were measured during baseline and a psychological challenge (a Stroop color-word matching task). Subjects underwent the Structured Clinical Interview for DSM-IV (SCID) and completed the Spielberger State-Trait Anxiety Inventory prior to testing. RESULTS: There was a significant main effect of maternal diagnostic group on FHR reactivity during the Stroop task even after controlling for birth weight and women's BP reactivity (F4,44 = 2.68, p =.04). Fetuses of depressed women had greater heart rate increases compared to fetuses of women with anxiety disorders and those of healthy, low-anxiety women (post hoc comparisons using the Fisher protected least significant difference test; t = 4.12, p <.05; t = 4.72, p <.01, respectively). There was a similar pattern comparing fetuses of healthy, high-anxiety women to the same two groups (t = 3.29, p <.05; t = 3.99, p <.05, respectively). There were no group differences in FHR during a resting baseline period (F4,52 = 1.2, p =.35). CONCLUSIONS: Maternal mood disturbance is associated with alterations in children's physiological reactivity prior to birth.