Nanoscale Three-Dimensional Imaging of Integrated Circuits Using a Scanning Electron Microscope and Transition-Edge Sensor Spectrometer.

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO2 integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed.

A tabletop X-ray tomography instrument for nanometer-scale imaging: reconstructions.

We show three-dimensional reconstructions of a region of an integrated circuit from a 130 nm copper process. The reconstructions employ x-ray computed tomography, measured with a new and innovative high-magnification x-ray microscope. The instrument uses a focused electron beam to generate x-rays in a 100 nm spot and energy-resolving x-ray detectors that minimize backgrounds and hold promise for the identification of materials within the sample. The x-ray generation target, a layer of platinum, is fabricated on the circuit wafer itself. A region of interest is imaged from a limited range of angles and without physically removing the region from the larger circuit. The reconstruction is consistent with the circuit's design file.

Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer.

BACKGROUND: Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this phase 1 trial were to evaluate safety and identify the recommended phase 2 dose of NFV added to concurrent CRT for locally advanced cervical cancer. METHODS: Two dose levels of NFV were evaluated: 875 mg orally twice daily (dose level 1 [DL1]) and 1250 mg twice daily (DL2). NFV was initiated 7 days before CRT and continued through CRT completion. Toxicity, radiographic responses, and pathologic responses were evaluated. Serial tumor biopsies (baseline, after NFV monotherapy, on NFV + CRT, and posttreatment) were evaluated by immunohistochemistry, NanoString, and reverse-phase-protein-array analyses. RESULTS: NFV sensitized cervical cancer cells to radiation, increasing apoptosis and tumor suppression in vivo. Patients (n = 13) with International Federation of Gynecology and Obstetrics stage IIA through IVA squamous cell cervical carcinoma were enrolled, including 7 patients at DL1 and 6 patients at DL2. At DL1, expansion to 6 patients was required after a patient developed a dose-limiting toxicity, whereas no dose-limiting toxicities occurred at DL2. Therefore, DL2 was established as the recommended phase 2 dose. All patients at DL2 completed CRT, and 1 of 6 experienced grade 3 or 4 anemia, nausea, and diarrhea. One recurrence was noted at DL2, with disease outside the radiation field. Ten of 11 evaluable patients remained without evidence of disease at a median follow-up of 50 months. NFV significantly decreased phosphorylated Akt levels in tumors. Cell cycle and cancer pathways also were reduced by NFV and CRT. CONCLUSIONS: NFV with CRT is well tolerated. The response rate is promising compared with historic controls in this patient population and warrants further investigation.

Design of a 3000-Pixel Transition-Edge Sensor X-Ray Spectrometer for Microcircuit Tomography.

Feature sizes in integrated circuits have decreased substantially over time, and it has become increasingly difficult to three-dimensionally image these complex circuits after fabrication. This can be important for process development, defect analysis, and detection of unexpected structures in externally sourced chips, among other applications. Here, we report on a non-destructive, tabletop approach that addresses this imaging problem through x-ray tomography, which we uniquely realize with an instrument that combines a scanning electron microscope (SEM) with a transition-edge sensor (TES) x-ray spectrometer. Our approach uses the highly focused SEM electron beam to generate a small x-ray generation region in a carefully designed target layer that is placed over the sample being tested. With the high collection efficiency and resolving power of a TES spectrometer, we can isolate x-rays generated in the target from background and trace their paths through regions of interest in the sample layers, providing information about the various materials along the x-ray paths through their attenuation functions. We have recently demonstrated our approach using a 240 Mo/Cu bilayer TES prototype instrument on a simplified test sample containing features with sizes of ∼ 1 µm. Currently, we are designing and building a 3000 Mo/Au bilayer TES spectrometer upgrade, which is expected to improve the imaging speed by factor of up to 60 through a combination of increased detector number and detector speed.

Diagnosis and Management of Adenocarcinoma in Situ: A Society of Gynecologic Oncology Evidence-Based Review and Recommendations.

This publication represents an extensive literature review with the goal of providing guidelines for the evaluation and management of cervical adenocarcinoma in situ (AIS). The authors drafted the guidelines on behalf of the Society of Gynecologic Oncology, and the guidelines have been reviewed and endorsed by the ASCCP. These guidelines harmonize with the ASCCP Risk-Based Management Consensus Guidelines and provide more specific guidance beyond that provided by the ASCCP guidelines. Examples of updates include recommendations to optimize the diagnostic excisional specimen, AIS management in the setting of positive compared with negative margins on the excisional specimen, surveillance and definitive management after fertility-sparing treatment, and management of AIS in pregnancy. The increasing incidence of AIS, its association with human papillomavirus-18 infection, challenges in diagnosis owing to frequent origin within the endocervical canal, and the possibility of skip lesions all make AIS a unique diagnosis whose management needs to be differentiated from the management of the more prevalent squamous cell dysplasia.

Causal effect of obesity on gynecologic malignancies.

INTRODUCTION: Gynecologic malignancies are estimated to affect 110,070 women and will be the cause of death in approximately 32,120 in 2018. Endometrial cancer is among the most prevalent with 63,320 estimated new cases and approximately 11,350 deaths, followed by ovarian cancer with an estimate of 22,000 new cases and 14,000 deaths annually. Obesity is one of the most modifiable risk factors. Providers should engage in a multifaceted approach to patient education and healthcare to decrease the projected cases of obesity-related cancers. BACKGROUND: The literature demonstrates a significant link between obesity and the development of certain malignancies such as endometrial, pancreatic, and renal cancer. Specific mechanisms found to play a role in the development of these malignancies include alterations of the metabolic pathway attributed to lipid accumulation as well as a chronic inflammatory process. Obesity also predisposes patients to other medical comorbidities as well as a poorer prognosis once a diagnosis of cancer is established. Factors contributing to poorer prognosis include challenges with treatment planning, specifically pertaining to inappropriate chemotherapy dosing and delivery of radiation therapy. Surgical approach and perioperative management are similarly challenging in obese patients and are associated with increased risk of complications. CONCLUSION: Obesity is a modifiable factor which is associated with an increased risk of cancer and poorer outcomes. Providers should educate patients on all health hazards of obesity, including increased risk of cancer, and encourage them to participate in a structured weight loss plan.

Promoting knowledge of cancer prevention and screening in an underserved Hispanic women population: a culturally sensitive education program.

This article aims to measure the baseline knowledge of cancer prevention, screening, and early detection practices, to understand the barriers to cancer screening and sources of health information; and to evaluate the effectiveness of a culturally sensitive education program in an underserved Hispanic women population. A total of 180 women participated. Pre- and postsurveys were administered. Multivariate analysis was used to analyze the impact of program on knowledge and to determine factors affecting learning. Results showed Significant overall improvement in knowledge of cancer symptoms (1.85 baseline vs. 3.67 postintervention, p < .001), knowledge of risk-reducing behaviors (2.71 vs. 4.81, p < .001); and effect on planned behavior (89% planned to follow screening guidelines). Higher incomes and younger age are associated with better learning. Major barriers to cancer screening were financial limitations and lack of knowledge. The intervention was effective in promoting awareness and knowledge of cancer screening and prevention. Programs aimed at reducing cancer incidence and mortality should recognize the importance of cultural sensitivity and facilitating access to screening tests.

Ethnic minorities exhibit reduction in door-to-balloon time comparable to whites with a newly-implemented emergency physician activation protocol (Code-STEMI).

BACKGROUND: Studies have shown significant differences in door-to-balloon times (D2B) for ethnic minority patients (minorities) undergoing angioplasty for ST-elevation myocardial infarction (STEMI) compared to white patients (white). In this study, we evaluated the D2B for these groups before and after modification of the emergency protocol for STEMI. METHODS: We compared D2B for 51 consecutive STEMIs during 2006, (serial activation protocol, SAP) with D2B times for 72 consecutive STEMI patients during 2007 when a "Code STEMI" (concurrent activation) protocol was instituted. Outcomes were D2B times in whites versus minorities, pre- and post-Code-STEMI, length of stay (LOS) and peak troponin I levels. RESULTS: The median D2B time in the SAP group was 113 (whites) vs. 122 (minorities) minutes (p = 0.324), as compared to 74 (whites) vs. 78 (minorities) minutes (p = 0.324) in the Code STEMI group. The D2B for both groups was significantly reduced (p < 0.0001) with the use of Code STEMI. The median peak troponin I in the SAP group was 97 ng/mL (whites) vs. 78 ng/mL (minorities) (p = 0.084), as compared to 54 ng/mL (whites) vs. 29 ng/mL (minorities) (p = 0.084) for the Code STEMI group. LOS was 4.88 days (whites) vs. 4.39 days (minorities) (p = 0.84) in the SAP group, as compared to 3.7 days (whites) vs. 3.4 days (minorities) (p = 0.84) for the Code STEMI group, a significant change (p = 0.012) for both groups. CONCLUSION: No ethnic disparity was observed in the mean D2B time, LOS and peak troponin I levels between whites and minorities; both groups demonstrated comparable improvement in all outcomes evaluated.

A leiomyoma in a cachectic woman presenting as a giant abdominal mass.

Fibroids are the most common gynecologic tumors. Our case discusses the outcome of a 47-year-old woman who presented to our clinic with cachexia, and a giant abdominal mass. An initial diagnostic imaging workup consisted of X-Ray, CT, and ultrasound and indicated a possible diagnosis of leiomyosarcoma. However, after surgical evaluation, she was diagnosed pathologically with an atypical presentation of a uterine leiomyoma. Our case reviews the epidemiology and presentation of both pathologies, along with the imaging workup, and the operative correlation in our patient.