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After Hurricane Laura struck the southeast coast of Louisiana in August 2020, the National Disaster Medical System (NDMS), a component of the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, deployed several 35-person disaster medical assistance teams in response to requests for medical support at 3 hospital locations that had been severely damaged in the storm. This was the first natural disaster medical deployment for NDMS during the coronavirus disease (COVID-19) pandemic. This article describes the modifications to the standard operating procedures that were made at 1 site to reduce the risk of infection to our patients and NDMS responders, including changes to the physical layout of the tenting, and alterations to the triage and treatment process.

Psychiatric illness is highly prevalent among children with epilepsy and most commonly manifests as attentional deficits, mood dysregulation, and social isolation. While epilepsy surgery is increasingly utilized for seizure control in children with medically refractory epilepsy, its consequences with regard to psychiatric outcomes are still somewhat obscure. Epilepsy surgery may influence psychiatric outcomes in myriad ways, including through improved seizure control, decreased reliance on antiepileptic drugs, and by altering the course of a child's neurodevelopmental trajectory. This review surveys the current literature to elucidate the complex interactions between epilepsy surgery and psychiatric outcomes and attempts to delineate the progression of psychiatric manifestations in surgical patients over time. When compared with medical treatment, epilepsy surgery yields better social and behavioral outcomes in the early postoperative period; however, it is not clear that surgery is superior when assessing long-term social and behavioral metrics. Additionally, epilepsy surgery has shown promise in improving long-term cognitive outcomes, but these effects may not become apparent until several years after surgery. Moreover, longer preoperative seizure duration tends to be associated with worse psychiatric outcomes. Finally, surgical patients may be particularly vulnerable to the deleterious psychiatric effects of ongoing seizures.

A Thesis presented to the Faculty of the Graduate School at the University of Missouri In Partial Fulfillment Of the Requirements for the Degree Master of Arts.

There is growing interest in applying glass as a substrate for 2.5D/3D applications. Glass has many material properties that make it well suited for interposer substrates. Glass based solutions provide significant opportunities for cost reduction by leveraging economies of scale as well as forming substrates at design thickness. A lot of work is being done to validate the value of glass as an interposer substrate. One important area is the electrical performance of glass relative to silicon. Because glass is an insulator, an interposer made with glass should have better electrical performance than one made with silicon. Electrical characterization and electrical models confirm this advantage, and its positive impact on functional performance. Further advantages are anticipated in reliability, driven by the ability to tailor thermal properties such as coefficient of thermal expansion (CTE) of glass. Modeling results will be presented that show how the proper choice of CTE can significantly lower stack warpage. Additionally, significant progress has been made in the demonstration of glass interposer fabrication. Fully patterned wafers and panels with through holes and blind holes are being fabricated today. It is equally important to be able to demonstrate the ability to leverage existing downstream processes for metallization of these substrates. The ability to apply existing downstream processes to make functional glass interposers using both through and blind via technology will be presented.

A new method for quantifying “sparkle” uses a simple measurement which includes a pixelated source, a test sample, and an eye simulator. The degree of sparkle is calculated from the standard deviation of the pixel powers across a portion of the display. Measurements show excellent correlation to human response studies.

Design, test, and performance requirement and analysis for a polarization-mode-dispersion compensator (PMDC) with four degrees of freedom is presented. The performance is analyzed on the basis of time-integrated and time-resolved bit-error ratio (BER) measurements. Signal impairments are generated by both, first- and higher-order emulators. The probability distributions of bit errors measured over many one second intervals exhibit very long tails. Therefore even a PMDC with a good average BER performance may result in a significant total outage time for a given system.

Hierarchical micro- and nanostructured surfaces have previously been made using a variety of materials and methods, including particle deposition, polymer molding, and the like. These surfaces have attracted a wide variety of interest for applications including reduced specular reflection and superhydrophobic surfaces. To the best of our knowledge, this paper reports the first monolithic, hierarchically structured glass surface that combines micro- and nanoscale surface features to simultaneously generate antiglare (AG), antireflection (AR), and superhydrophobic properties. The AG microstructure mechanically protects the AR nanostructure during wiping and smudging, while the uniform composition of the substrate and the micro- and nanostructured surface enables ion exchange through the surface, so that both the substrate and structured surface can be simultaneously chemically strengthened.

There is growing interest in applying glass as a substrate for 2.5D/3D applications. Glass has many material properties that make it well suited for interposer substrates. Glass based solutions provide significant opportunities for cost benefits by leveraging economies of scale as well as forming substrates at design thickness. A lot of work is being done to validate the value of glass as an interposer substrate. One important area is the electrical performance of glass relative to silicon. Because glass is an insulator, it is expected to have better electrical performance than silicon. Electrical characterization and electrical models demonstrate the advantages of the insulating properties of glass, and its positive impact on functional performance. Further advantages are anticipated in reliability performance, because of the ability to adjust thermal properties such as coefficient of thermal expansion (CTE) of glass. Modeling results demonstrating these improvements will be presented. Additionally, significant progress has been made in the demonstration of glass interposer fabrication. Fully patterned wafers and panels with through holes and blind holes are being fabricated today. Leveraging existing downstream processes for metallization on these substrates is also important for cost effectiveness and ease of transition into production. Progress on demonstrating the ability to leverage existing downstream processes to make functional glass interposers using both through and blind via technology will be presented.

Over the past several years, the semiconductor industry has seen some tremendous developments in using glass as an interposer substrate. Glass has many properties that make it an ideal substrate for interposer substrates such as: ultra-high resistivity, low dielectric constant, ultra-low electrical loss and adjustable coefficient of thermal expansion (CTE) that allows management of 3D-IC stacks. Regardless of technical performance, any glass based solution must also provide significant cost advantages in substrate material, via formation, and subsequent processing. Cost-Effective Solutions In this paper, we will cover how fusion formed glass provides cost-effective solutions for the manufacturing of interposer materials for as-formed 100 μm precision substrate with a pristine surface, without the need for polishing, thus eliminating the manufacturing steps for polishing and thinning. Design Considerations For effective implementation of glass substrates, processing costs for through-glass-vias (TGV) on ultra-thin glass is also a challenge. This paper will reference data from several different designs to demonstrate the impact of design on Corning's TGV process cost relative to silicon solutions. It will also highlight processing lessons learned in fabricating TGV interposers from bare glass into complete packaged test vehicles and their impact on cost. Via Capabilities Furthermore, glasses via formation capabilities have dramatically improved over the past several months. Fully populated wafers with >100,000 through and blind holes (25 μm diameter) are fabricated today with 20μm diameters. We report on the significant enhancements demonstrated on important quality parameters. We will also report on strength parameters measured on TGV wafers and positive implications with respect to product reliability.

Glass has many properties that make it an ideal substrate for important 3D-IC applications such as interposer substrates and glass carrier wafers. Critical material properties such as: ultra-high resistivity, low dielectric constant, ultra-low electrical loss and tailorable CTE, provide unique advantages. Forming processes such as the fusion forming process provide additional advantages around the ability to deliver low total thickness variation (TTV) without downstream grinding and polishing processes providing positive implications on both cost and performance. The ability to scale substrate sizes in size (450 mm wafers, panels) and thickness (down to 100 um) as well as panels provides tremendous advantages for the ability to scale for high volume manufacture. Just as important as being able to provide glass with these important attributes, is the ability to properly characterize them. We provide a summary highlighting the importance of the glass attributes in glass interposer and carrier applications, as well as implications of using the appropriate metrology solution to characterize them.

Through-substrate vias (TSV) are critical for Three-Dimensional Stacked Integrated Circuits (3DS-IC) integration. While silicon traditionally has been used in this application, glass has properties that make it a very intriguing material for through substrate via applications. We note that the term glass describes a broad material set, with a wide range of properties driven by composition. For example, compositional changes allow tailoring of mechanical and thermal properties. Furthermore, novel forming processes available today enable reduction or elimination of time consuming and costly thinning or polishing processes, as well as opportunities to more easily scale the footprint of the substrate. Significant progress has been made to develop techniques to provide suitable through holes for vias in different glass compositions, which leverages the versatility of glass to create a substrate for TSV.

The wavelength tunable 1060-nm distributed Bragg reflector (DBR) laser chip consists of three sections: a gain section for lasing, and phase and DBR sections for wavelength control. A micro-heater is lithographically integrated on the top of the DBR section to tune the emission wavelength. The phase section is designed with either a top heater or by current injection to provide fine tuning of the wavelength. The wavelength tuning efficiency of our DBR laser is approximately 9 nm/W at the laser heat sink temperature of 25°C. Single-mode output powers of 686 mW and 605 mW were obtained at a CW gain drive current of 1.25 A and heat sink temperatures of 25°C and 60°C, respectively. Gain-switching by applying 1.1 GHz sinusoidal signal mixed with 600 mA DC injection current produced approximately 58 ps long optical pulses with 3.1 W peak power and 228 mW average power. The average power increased to 267 mW and pulse width broadened to 70 ps with DC bias of 700 mA. In CW operation, one of the applications for high-power single-mode DBR lasers is for non-linear frequency conversion. The light emitted from the 1060-nm DBR laser chip was coupled into a single-mode periodically poled lithium niobate (PPLN) crystal waveguide. Up to 350 mW optical power at 530 nm with the wall-plug efficiency of up to 15% was demonstrated.

We report a compact green light source consisting of a 1060-nm DBR laser, a periodically poled lithium niobate crystal waveguide and an adaptive optic element consisting of a micro-electro-mechanical system actuator. Up to 350 mW optical power at 530 nm with the wallplug efficiency of up to 15% was demonstrated. The change in the optical power at constant current over the temperature range from 10°C to 70°C was less than 18%.

The United States remains unprepared to cope with the possibility of an attack on a major city by terrorists capable of acquiring and detonating an improvised nuclear device. Long-held anxieties about the non-survivability of nuclear war promulgated during the intense U.S.—Soviet arms race from the late 1940s through the 1980s, and reluctance to consider low probability/high consequence events among local disaster planning priorities, are barriers to developing plans that could dramatically save lives in the event of a terrorist-based nuclear detonation. This paper begins by describing the reality of the threat of nuclear terrorism to the United States and the enormous scale of lives lost and physical destruction that would result from the detonation of even a small improvised nuclear device (IND) in an American city. It then systematically lays out the gross inadequacy of current response capabilities, and highlights the critical unmet need for urgent, deliberate and well-funded planning efforts to address those deficiencies. In the Recommendations section, Columbia University‘s National Center for Disaster Preparedness (NCDP) calls for targeted public health and medical care regional planning and response efforts focused on “gray zones“ —areas where significant life-saving opportunities would exist following an IND detonation, and where preparedness planning and proper training can meaningfully enhance survival and recovery.

This is the third consensus document in an ongoing process to convene experts from the multiple disciplines that are involved in the planning for children affected by disasters.

This thesis addresses the role of subgroups and sub-populations in drug development and regulation and includes the critical appraisal of regulatory guidance.Chapter One introduces clinical trial methodology and describes the current regulatory environment.In Chapter Two, randomisation is reviewed in relation to unbiased estimation of treatment differences and the impact of data exclusion to form subsets is described.Simpson's paradox (SP) is considered in Chapter Three. Randomisation is shown to protect against SP, while a treatment by factor interaction is not required. Balance is redefined for the odds formulation leading to identical unconditional and conditional parameters. The chances of SP (and less extreme inconsistencies) occurring are quantified using simulation, with varying sample size.Chapter Four considers treatment by subgroup interactions. Suggestions regarding the magnitude of a clinically relevant interaction are presented while a simple Bayesian approach to evaluate interactions using margins for the interaction parameter is applied to published data.Chapter Five considers non-inferiority in relation to sub-populations and covariate adjustment for binary outcomes. It is shown that the Per Protocol population is not necessarily conservative and simulation is used to demonstrate the impact on the type I and II errors. Using simulations it is shown that an increase in the type I error occurs if an important covariate is excluded from the logistic model when testing for non-inferiority.Chapter Six is directed towards the sub-population of children. The impact of off-label treatment is discussed in relation to the ethics of placebo-controlled trials, together with the importance of randomisation in evaluating long-term safety.In Chapter Seven, a therapeutic area is selected to ilJustrate the challenges raised during the previous chapters and wording changes to current regulatory guidelines are proposed.The thesis closes with personal thoughts regarding the future potential for individualised treatment.

© Journal of Sports Science and Medicine. The physical demands of fast-medium bowling are increasingly being recognised, yet comparative exploration of the differing demands between competitive formats (i.e. one-day [OD] versus multi-day [MD] matches) remain minimal. The aim of this study was to describe in-match physiological profiles of professional fast-medium bowlers from England across different versions of competitive matches using a multivariable wearable monitoring device. Seven professional cricket fast-medium bowlers wore the Bioharness™ monitoring device during matches, over three seasons (>80 hours in-match). Heart Rate (HR) and Accel-eromety (ACC) was compared across match types (OD, MD) and different in-match activity states (Bowling, Between over bowling, Fielding). Peak acceleration during OD bowling was significantly higher in comparison to MD cricket ([OD vs. MD] 234.1 ± 57.9 vs 226.6 ± 32.9 ct·episode-1, p < 0.05, ES = 0.11-0.30). Data for ACC were also higher during OD than MD fielding activities (p < 0.01, ES = 0.11-.30). OD bowling stimulated higher mean HR responses (143 ± 14 vs 137 ± 16 beats·min-1, p < 0.05, ES = 0.21) when compared to MD matches. This increase in OD cricket was evident for both between over (129 ± 9 vs 120 ± 13 beats·min-1,p < 0.01, ES = 0.11-0.50) and during fielding (115 ± 12 vs 106 ± 12 beats·min-1, p < 0.01, ES = 0.36) activity. The increased HR and ACC evident in OD matches suggest greater acute physical loads than MD formats. Therefore, use of wearable technology and the findings provided give a valuable appreciation of the differences in match loads, and thus required physiological preparation and recovery in fast-medium bowlers.

Objective: Fusobacterium nucleatum (F. nucleatum) is a microbial pathogen that contributes to the initiation and progression of colorectal cancer. Although evidence points to its immunosuppressive effects in colorectal cancer, F. nucleatum has been associated with high-level microsatellite instability (MSI) which is characterized by intense immune response. We hypothesized that the association of F. nucleatum with local immunosuppression might be stronger in tumors with high-level MSI or a high neoantigen load, which is a direct consequence of MSI that influences tumor-immune interactions. Design: We utilized molecular pathological epidemiology database of 1,027 colon and rectal cancer cases in the Nurses’ Health Study and the Health Professionals Follow-up Study. We assessed the association of F. nucleatum (negative, low, or high) with tumor immunity status in strata of MSl status. We measured F. nucleatum DNA in tumor tissue using quantitative PCR. As immunity status, we evaluated hystopathological lymphocytic reaction (tumor-infiltrating lymphocytes [TIL], intratumoral periglandular reaction, peritumoral lymphocytic reaction, or Crohn's-like lymphoid reaction) and measured T cell densities (CD3+, CD8+, CD45RO [PTPRC]+ or FOXP3+ cells) using immunohistochemistry and computer-assisted image analysis. Logistic regression model was used to adjust for potential confounders, including CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Using whole-exome sequencing data (N = 586), we conducted secondary analyses to assess the interaction of F. nucleatum with a neoantigen load. Results: The association between F. nucleatum and TIL differed by MSI status (P for interaction = 0.0017; with the adjusted α level of 0.006). Compared with F. nucleaum-negative cases, F. nucleatum-positive cases were associated with low-level TIL in MSI-high tumors (odds ratio, 0.40 [95% confidence interval, 0.14-1.08] and 0.40 [95% confidence interval, 0.17-0.97] for F. nucleaum low and high cases, respectively), but not in microsatellite stable/MSI-low tumors. We did not find any interaction between F. nucleatum and MSI status in T cell subsets. The association between F. nucleatum and TIL did not differ significantly by levels of a neoantigen load (P for interaction = 0.015). Conclusions: The association of F. nucleatum with the immunosuppressive microenvironment may be stronger in colorectal cancer with high-level MSI. Our findings suggest the interplay between F. nucleatum and MSI status in host immune response to the tumor. Citation Format: Kosuke Mima, Tsuyoshi Hamada, Reiko Nishihara, Jonathan Nowak, Zhi Rong Qian, Keisuke Kosumi, Marios Giannakis, Susan Bullman, Hideo Baba, Curtis Huttenhower, Wendy Garrett, Andrew Chan, Matthew Meyerson, Charles Fuchs, Shuji Ogino. Fusobacterium nucleatum and tumor immunity status according to microsatellite instability in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4560. doi:10.1158/1538-7445.AM2017-4560