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.

Accu-Beads as a quality control measure for manual and automated methods of measuring sperm concentration-an observational study.

PURPOSE: To determine the precision and accuracy of Accu-Beads and their utility as a quality control product for manual and automated measurements of sperm concentration. METHODS: This observational study was performed at an Assisted Reproductive Technology laboratory in a tertiary-care, university hospital. To simulate sperm concentration, bead concentrations were measured with the use of a manual and an automated method. RESULTS: The manual counts did not vary significantly from the automated counts regardless of the concentration. However, the counts did vary between lots of low concentration of Accu-Beads and between the two different types of fixed counting chambers. The two bead concentrations used in this study were below the 95 % confidence interval for the values listed by the manufacturer. CONCLUSION(S): In our laboratory, Accu-Beads met enough of the requirements of a good control material to be acceptable for daily quality control use, especially if we set our own ranges of acceptability for each vial of Accu-Beads. It is necessary to evaluate each new lot of Accu-Beads when they are received and again if they are used with a different counting chamber.

Evaluation of a New Adolescent Social Communication Assessment: The Transition Pragmatics Interview.

PURPOSE: This study evaluated the psychometric functioning of a new criterion-referenced assessment of adolescent social communication, the Transition Pragmatics Interview (TPI), based on the synthesis model of pragmatics. Two ways of interpreting item difficulty were explored: (a) as a function of the synthesis model elements of social communication ability that items were designed to assess, and (b) as a function of the developmental level required for a successful response based on an adapted situational-discourse-semantics (SDS) model (Norris & Hoffman, 1993). METHOD: Thirty-seven participants aged 14-22 years completed the TPI. Responses were analyzed using Rasch analysis to evaluate the functioning of the scale and to determine item difficulty. Items were coded for the SDS developmental level required for an adequate response. The mean Rasch item difficulty for items at each SDS developmental level was analyzed for the five adapted SDS domains. RESULTS: Consistent with the first approach for interpreting item difficulty, TPI items varied in difficulty as a function of the element of social communication they were designed to assess (p < .001). Interpreting item difficulty based on the adapted SDS model was not supported: Items requiring higher SDS developmental levels were not more difficult than those requiring less (p = .55). CONCLUSIONS: The TPI responses fit the Rasch model, supporting the TPI as a unidimensional measure and supporting the use of all items together to compute a single number that summarizes the level of social communication for each examinee. The item ordering from least to most difficult was consistent with prior findings on adolescent social communication development. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26018545.

The heat is on: room temperature affects laboratory equipment--an observational study.

OBJECTIVE: To evaluate the effect of ambient room temperature on equipment typically used in in vitro fertilization (IVF). DESIGN: We set the control temperature of the room to 20 °C (+/-0.3) and used CIMScan probes to record temperatures of the following equipment: six microscope heating stages, four incubators, five slide warmers and three heating blocks. We then increased the room temperature to 26 °C (+/-0.3) or decreased it to 17 °C (+/-0.3) and monitored the same equipment again. We wanted to determine what role, if any, changing room temperature has on equipment temperature fluctuation. RESULTS: There was a direct relationship between room temperature and equipment temperature stability. When room temperature increased or decreased, equipment temperature reacted in a corresponding manner. Statistical differences between equipment were found when the room temperature changed. What is also noteworthy is that temperature of equipment responded within 5 min to a change in room temperature. CONCLUSIONS: Clearly, it is necessary to be aware of the affect of room temperature on equipment when performing assisted reproductive procedures. Room and equipment temperatures should be monitored faithfully and adjusted as frequently as needed, so that consistent culture conditions can be maintained. If more stringent temperature control can be achieved, human assisted reproduction success rates may improve.

Temperature variations within and between incubators-a prospective, observational study.

PURPOSE: To determine if there is a temperature variation within and between incubators. METHODS: This prospective, experimental trial with external controls was performed at an Assisted Reproductive Technology laboratory in a tertiary-care, university hospital. Temperature values were taken at various locations within and between incubators. RESULTS: Even though they were both set to 37.0 °C, the same make and model incubators had significantly different internal temperatures. Temperatures differed significantly among top, middle and bottom shelves and between fronts and backs of shelves. CONCLUSION(S): We found temperatures differed within and between our front-loading incubators. Thus, laboratory personnel should evaluate their incubators for temperature variations within and between incubators and, if temperatures differ significantly, develop a plan to deal with discrepancies.

Altering the viscoelastic properties of mucus-grown Pseudomonas aeruginosa biofilms affects antibiotic susceptibility.

The viscoelastic properties of biofilms are correlated with their susceptibility to mechanical and chemical stress, and the airway environment in muco-obstructive pulmonary diseases (MOPD) facilitates robust biofilm formation. Hyperconcentrated, viscoelastic mucus promotes chronic inflammation and infection, resulting in increased mucin and DNA concentrations. The viscoelastic properties of biofilms are regulated by biopolymers, including polysaccharides and DNA, and influence responses to antibiotics and phagocytosis. We hypothesize that targeted modulation of biofilm rheology will compromise structural integrity and increase antibiotic susceptibility and mucociliary transport. We evaluate biofilm rheology on the macro, micro, and nano scale as a function of treatment with a reducing agent, a biopolymer, and/or tobramycin to define the relationship between the viscoelastic properties of biofilms and susceptibility. Disruption of the biofilm architecture is associated with altered macroscopic and microscopic moduli, rapid vector permeability, increased antibiotic susceptibility, and improved mucociliary transport, suggesting that biofilm modulating therapeutics will improve the treatment of chronic respiratory infections in MOPD.

Delivery Characterization of SPL84 Inhaled Antisense Oligonucleotide Drug for 3849 + 10 kb C- > T Cystic Fibrosis Patients.

Recent advances in the therapeutic potential of RNA-related treatments, specifically for antisense oligonucleotide (ASO)-based drugs, have led to increased numbers of ASO regulatory approvals. In this study, we focus on SPL84, an inhaled ASO-based drug, developed for the treatment of the pulmonary disease cystic fibrosis (CF). Pulmonary drug delivery is challenging, due to a variety of biological, physical, chemical, and structural barriers, especially when targeting the cell nucleus. The distribution of SPL84 throughout the lungs, penetration into the epithelial cells and nucleus, and structural stability are critical parameters that will impact drug efficacy in a clinical setting. In this study, we demonstrate broad distribution, as well as cell and nucleus penetration of SPL84 in mouse and monkey lungs. In vivo and in vitro studies confirmed the stability of our inhaled drug in CF patient-derived mucus and in lung lysosomal extracts. The mobility of SPL84 through hyperconcentrated mucus was also demonstrated. Our results, supported by a promising preclinical pharmacological effect of full restoration of cystic fibrosis transmembrane conductance regulator channel activity, emphasize the high potential of SPL84 as an effective drug for the treatment of CF patients. In addition, successfully tackling the lung distribution of SPL84 offers immense opportunities for further development of SpliSense's inhaled ASO-based drugs for unmet needs in pulmonary diseases.

Changes in long luteal protocol affects the number of days of stimulation: evolution of an assisted reproductive technology practice.

OBJECTIVE: To determine if the types of drugs used in controlled ovarian hyperstimulation influence the number of days of stimulation. STUDY DESIGN: This retrospective study of couples presenting at an assisted reproductive technology (ART) facility January 1997 through December 2007 included patients who were < 40 years of age, had a body mass index (BMI) of 20-35, used fresh sperm or oocytes, had > or = 3 embryos available on day 3, never had previous ART, and did not use a gestational carrier. Data analysis was limited to patients treated with long luteal stimulation. Data were separated into two groups: patients stimulated with urinary drugs and those stimulated with recombinant drugs. RESULTS: The groups were not different in age and day 3 follicle-stimulating hormone values, but were different in BMI, diagnoses, and fertilization methods. There were a significantly greater number of days of stimulation, total number of follicles produced, and peak estradiol level in the recombinant group. The recombinant group had less drug given per day, less endometrial thickness, and fewer embryos transferred. CONCLUSION: A change in our long luteal stimulation protocol appears to have lengthened the days of stimulation for our patients without altering pregnancy rate.

Validating the Persian Intuitive Eating Scale-2 Among Breast Cancer Survivors Who Are Overweight/Obese.

Women with breast cancer are at risk of being overweight/obese which may consequently increase mortality. Intuitive eating is an adaptive eating behavior which might be beneficial for weight outcomes. The present study validated the Persian Intuitive Eating Scale-2 (IES-2) among overweight/obese Iranian females with breast cancer. Women who were overweight/obese with breast cancer (n = 762; mean ± SD age = 55.1 ± 5.7 years) completed the following questionnaires: IES-2, General Self-Efficacy Scale (GSE-6), Hospital Anxiety and Depression Scale (HADS), Short Form-12 (SF-12), Weight Bias Internalization Scale (WBIS), Body Appreciation Scale-2 (BAS-2), and Eating Attitudes Test (EAT-26). Confirmatory factor analysis (CFA) and Rasch analysis were applied to examine the psychometric properties of the IES-2. Associations between IES-2 score and other scale scores were assessed. CFA and Rasch analysis suggested that the Persian IES-2 had robust psychometric properties and all IES-2 items were meaningful in their embedded domains. The four-factor structure of the Persian IES-2 was confirmed. Concurrent validity was supported by the positive correlations between the IES-2 score and scores on the GSE-6, SF-12 mental component, and BAS-2. Negative correlations were found between the IES-2 score and the HADS (anxiety and depression subscales), WBIS, and EAT-26. The present study demonstrated that the Persian IES-2 is a well-designed instrument and is applicable for women who are overweight/obese with breast cancer.

Rasch Analysis for Instrument Development: Why, When, and How?

This essay describes Rasch analysis psychometric techniques and how such techniques can be used by life sciences education researchers to guide the development and use of surveys and tests. Specifically, Rasch techniques can be used to document and evaluate the measurement functioning of such instruments. Rasch techniques also allow researchers to construct "Wright maps" to explain the meaning of a test score or survey score and develop alternative forms of tests and surveys. Rasch techniques provide a mechanism by which the quality of life sciences-related tests and surveys can be optimized and the techniques can be used to provide a context (e.g., what topics a student has mastered) when explaining test and survey results.

Effects of Panax ginseng, zearalenol, and estradiol on sperm function.

BACKGROUND: Estrogen signaling pathways are modulated by exogenous factors. Panax ginseng exerts multiple activities in biological systems and is classified as an adaptogen. Zearalenol is a potent mycoestrogen that may be present in herbs and crops arising from contamination or endophytic association. The goal of this study was to investigate the impact of P. ginseng, zearalenol and estradiol in tests on spermatozoal function. METHODS: The affinity of these compounds for estrogen receptor (ER)-alpha and beta (ERα and ERß)-was assessed in receptor binding assays. Functional tests on boar spermatozoa motility, movement and kinematic parameters were conducted using a computer-assisted sperm analyzer. Tests for capacitation, acrosome reaction (AR), and chromatin decondensation in spermatozoa were performed using microscopic analysis. RESULTS: Zearalenol-but not estradiol (E2)- or ginseng-treated spermatozoa-decreased the percentage of overall, progressive, and rapid motile cells. Zearalenol also decreased spontaneous AR and increased chromatin decondensation. Ginseng decreased chromatin decondensation in response to calcium ionophore and decreased AR in response to progesterone (P4) and ionophore. CONCLUSION: Zearalenol has adverse effects on sperm motility and function by targeting multiple signaling cascades, including P4, E2, and calcium pathways. Ginseng protects against chromatin damage and thus may be beneficial to reproductive fitness.

Changes in the freezing protocol for human zygotes alter embryonic development and pregnancy rates.

OBJECTIVE: To determine the effect of various freezing protocols on postthaw development and pregnancy rates resulting from transfer of human zygotes. DESIGN: Prospective study. SETTING: Tertiary care center. PATIENT(S): Couples undergoing assisted reproductive technology (ART) procedures who wished to have their excess zygotes cryopreserved. INTERVENTION(S): We cryopreserved zygotes with one of three protocols. MAIN OUTCOME MEASURE(S): Post-thaw survival and development of the zygotes as well as pregnancy rate after transfer of these zygotes. RESULT(S): A 3-minute hold time after seeding, followed by a final preplunging temperature of -180 degrees C, resulted in a clinical pregnancy rate of 28.6%. In contrast, a 15-minute postseed hold time and a -30 degrees C final chamber temperature resulted in a 37.3% clinical pregnancy rate. When we combined the protocols to provide a 15-minute postseed holding time and a -180 degrees C before plunging into liquid nitrogen, we achieved a 69.6% clinical pregnancy rate. CONCLUSION(S): By increasing the postseeding hold time and decreasing the temperature of the freezing chamber before plunging the zygotes into liquid nitrogen, significant improvements can be made in postthaw development and pregnancy rates.

Impact of kudzu and puerarin on sperm function.

The goal of this study was to investigate the impact of kudzu (Pueraria mirifica) and the isoflavone puerarin in functional toxicological tests on spermatozoa and to assess the affinity of extracts and pure isoflavones for estrogen receptor (ER)-alpha and -beta (ERα, ERß) in receptor binding assays. Capacitation, acrosome reaction and chromatin decondensation in spermatozoa were analyzed using microscopic analysis. Kudzu, but not puerarin, reduced motility of sperm. Puerarin reduced the percent spontaneous acrosome reaction in spermatozoa. The pathways used by kudzu that affect sperm function are not fully mirrored by puerarin. Puerarin, kudzu and its other phytoestrogenic components displayed preferential affinity for ERß, however the diverse effects of kudzu and puerarin on sperm function implicate the involvement of multiple signaling systems.

Expectations for oocyte fertilization and embryo cleavage after whole sperm versus sperm head intracytoplasmic sperm injection.

OBJECTIVE: To compare oocyte fertilization and embryo development after intracytoplasmic sperm injection (ICSI) with a whole sperm vs. a sperm head. DESIGN: Retrospective study. SETTING: Hospital-based IVF practice. PATIENT(S): Fifty-three women undergoing 54 IVF-embryo transfer plus ICSI procedures between January 1999 and June 2002. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Oocyte fertilization, zygote cleavage, and embryo stage after 72 hours of culture. RESULT(S): A significantly higher fertilization rate was observed using whole sperm (72.2%) than when using sperm heads (56.4%). Zygote cleavage rates for whole sperm vs. sperm head ICSI were 96.4% and 92.7%, respectively. Embryo cell stage after 72 hours of culture for whole sperm vs. sperm head ICSI was 6.5 +/- 2.1 cells and 5.6 +/- 1.8 cells, respectively. Embryo grade at this same time point was not different (2.3 +/- 1.0 and 2.5 +/- 0.9, respectively). CONCLUSION(S): The ICSI using whole sperm produces superior fertilization rates compared to ICSI using sperm heads, but once oocytes were fertilized, zygote cleavage rates were not different between the two sperm sources. Oocytes injected with a whole sperm produced embryos of higher cell stage but equivalent quality compared to oocytes injected with sperm heads. Therefore, having only sperm heads for use in ICSI should not be a deterrent to using this procedure.

Conclusions about the effects on fertilization of time from aspiration to incubation and blood in the aspirate depend on the use of appropriate statistical techniques.

OBJECTIVE: To examine the effects of exposure to blood and time from aspiration to incubation on oocyte fertilization. DESIGN: Retrospective, cohort study. SETTING: Hospital-based IVF practice. PATIENT(S): Eighty-two women undergoing IVF procedures. INTERVENTION(S): Patients received a standard gonadotropin protocol or a microdose flare protocol. MAIN OUTCOMES MEASURE(S): Logistic regression was used to estimate odds of nonfertilization, adjusting for maternal age, time from aspiration to incubation, presence of blood in the aspirate, and a time-by-blood interaction. Two statistical methods were used: an analysis that assumed oocytes were independent and an analysis that adjusted for the lack of independence of oocytes within mothers (i.e., cluster-correlated data). RESULT(S): The 82 women contributed 1093 oocytes. In a model with blood dicotomized as present or absent, and with time elapsed and maternal age categorized into quartiles, both time and maternal age were statistically significant when conventional logistic regression was used. In analyses that accounted for clustering within mother, retrieval-to-incubation times more than 4 minutes were associated with an increased risk of nonfertilization, but age and blood were not; there was no evidence of an interaction between time elapsed and blood. CONCLUSION(S): If appropriate statistics are applied, retrieval-to-incubation times more than 4 minutes are associated with increased risk of nonfertilization.

Breeding behavior of the American black bear Ursus americanus.

By means of videotape, we observed and timed courtship, mating, and refractoriness in the American black bear while confined in a semicaptive environment. Sixty-six courtships resulted in mating. During courtship, the male detected estrus and receptivity in the female. Courtship lasted 22.5+/-2.3s (mean+/-S.E.M.). We videotaped and reviewed 61 matings that included mounts, pelvic thrusts, and flutters. Mating lasted 51.6+/-4.2s. Within these 61 matings, there were 24 pelvic thrusts and 14 flutters observed. Pelvic thrusts averaged 2.3+/-0.3 times, while flutters averaged 11.1+/-2.9 times. Of the 61 courtship-mating segments, 28 segments depicted a male refractory period, while 27 segments depicted a female refractory period. The male refractory period lasted 44.9+/-6.1s during which the male sat and licked his genital region. The female walked, ran away, or turned and attacked the male during her 54.2+/-8.3s refractory period. This is the first time a large number of paired ursid matings has been described and timed.

Evidence that bears are induced ovulators.

The objective of this study was to determine if black bears are induced ovulators. We conducted a single experiment with two replicates; each replicate was divided into two arms: females exposed to male bears and females without male exposure. We used laparoscopy to examine ovaries for corpora lutea and measured serum progesterone concentrations. Six of the seven isolated females failed to ovulate, while seven of the eight females exposed to males produced one to four corpora lutea. Furthermore, isolated females had significantly lower progesterone concentrations than females exposed to males. Thus, our data suggest that the American black bear is an induced ovulator. These results may aid biologists in their efforts to reproduce ursids in controlled environments.

Using OSCE-based evaluation: curricular impact over time.

The Objective Structured Clinical Examination (OSCE) is becoming more widely used for performance assessment in dentistry. The department of pediatric dentistry at Baylor College of Dentistry (BCD) began incorporating the OSCE into its curriculum in 1995. This article describes the evolution of the department's use of the OSCE and its impact on teaching and the curriculum. The discussion focuses on logistics and station design, curricular content and order, student anxiety, writing and scoring exams, and curriculum assessment. BCD has found that using an OSCE-based testing format is time-consuming and labor-intensive, but provides unprecedented feedback about students' understanding and pinpoints areas of confusion. The demands of an OSCE-based testing format reveal that students can master, to the level of competency, only a finite amount of information in a given time period. The timed, interactive aspects of the OSCE create high levels of student anxiety that must be addressed. Writing and scoring OSCE items are different from traditional test items. The OSCE is a valuable mechanism to assess the students' progress toward competency. This review of the process of incorporating OSCEs into a curriculum is the foundation for future assessment of the OSCE and its use for curricular improvement.