Purpose Men with azoospermia and severe testicular atrophy may be counseled to avoid sperm retrieval due to perceived limited success. We evaluated the outcomes of microdissection testicular sperm ...extraction in men with severe testicular atrophy (volume 2 ml or less). Materials and Methods We reviewed the records of 1,127 men with nonobstructive azoospermia who underwent microdissection testicular sperm extraction followed by intracytoplasmic sperm injection. They were classified into 3 groups based on average testicular volume, including 2 ml or less, greater than 2 to less than 10 and 10 or greater. Sperm retrieval, clinical pregnancy and live birth rates were calculated. Clinical features evaluated included age, follicle-stimulating hormone level, cryptorchidism history, Klinefelter syndrome, varicocele and testicular histology on diagnostic biopsy. Results Testicular sperm were successfully retrieved in 56% of the men. The sperm retrieval rate in those with a testicular volume of 2 ml or less, greater than 2 to less than 10 and 10 or greater was 55%, 56% and 55%, respectively. Clinical pregnancy and live birth rates were similar in men in the 3 groups who underwent sperm retrieval (55.2%, 50.0% and 47.0%, and 47.2%, 43.0% and 42.2%, respectively). Of the 106 men with an average testis volume of 2 ml or less those from whom sperm were retrieved were younger (31.1 vs 35.2 years) and more likely to have a history of Klinefelter syndrome (82.2% vs 55.6%) than men in whom sperm were not found (p <0.05). Men in this group had a higher prevalence of Klinefelter syndrome than men with a testis volume of greater than 2 ml (72.6% vs 5.3%, p <0.0001). Men younger than 30 years with Klinefelter syndrome had a higher sperm retrieval rate than men older than 30 years without Klinefelter syndrome (81.8% vs 33%, p <0.01). There was no cutoff point for age beyond which sperm could not be retrieved in men with small testes. On multivariable analysis younger age was the only preoperative factor associated with successful sperm retrieval in men with small testes (2 ml or less). Conclusions Testicular volume does not affect the sperm retrieval rate at our center for microdissection testicular sperm extraction. Of men with the smallest volume testes those who were younger with Klinefelter syndrome had the highest sperm retrieval rate. Severe testicular atrophy should not be a contraindication to microdissection testicular sperm extraction.
Developed and developing economies alike face increased resource scarcity and competitive rivalry. In this context, science and technology appear as an essential source of competitive and sustainable ...advantage at national and regional levels. However, the key determinant of their efficacy is the quality and quantity of entrepreneurship-enabled innovation that unlocks and captures the benefits of the science enterprise in the form of private, public or hybrid goods. Linking basic and applied research with the market, via technology transfer and commercialization mechanisms, including government-university-industry partnerships and capital investments, constitutes the essential trigger mechanism and driving force of sustainable competitive advantage and prosperity. In this volume, the authors define the terms and principles of knowledge creation, diffusion, and use, and establish a theoretical framework for their study. In particular, they focus on the "Quadruple Helix model, through which government, academia, industry, and civil society are seen as key actors promoting a democratic approach to innovation through which strategy development and decision making are exposed to feedback from key stakeholders, resulting in socially accountable policies and practices.
Abstract Objectives: To assess the methodological quality of intention to treat analysis as reported in randomised controlled trials in four large medical journals. Design: Survey of all reports of ...randomised controlled trials published in 1997 in the BMJ, Lancet, JAMA, and New England Journal of Medicine. Main outcome measures: Methods of dealing with deviations from random allocation and missing data. Results: 119 (48%) of the reports mentioned intention to treat analysis. Of these, 12 excluded any patients who did not start the allocated intervention and three did not analyse all randomised subjects as allocated. Five reports explicitly stated that there were no deviations from random allocation. The remaining 99 reports seemed to analyse according to random allocation, but only 34 of these explicitly stated this. 89 (75%) trials had some missing data on the primary outcome variable. The methods used to deal with this were generally inadequate, potentially leading to a biased treatment effect. 29 (24%) trials had more than 10% of responses missing for the primary outcome, the methodsof handling the missing responses were similar in this subset. Conclusions: The intention to treat approach is often inadequately described and inadequately applied. Authors should explicitly describe the handling of deviations from randomised allocation and missing responses and discuss the potential effect of any missing response. Readers should critically assess the validity of reported intention to treat analyses. Key messages Intention to treat gives a pragmatic estimate of the benefit of a change in treatment policy rather than of potential benefit in patients who receive treatment exactly as planned Full application of intention to treat is possible only when complete outcome data are available for all randomised subjects About half of all published reports of randomised controlled trials stated that intention to treat was used, but handling of deviations from randomised allocation varied widely Many trials had some missing data on the primary outcome variable, and methods used to deal with this were generally inadequate, potentially leading to bias Intention to treat analyses are often inadequately described and inadequately applied
During the infectious process, bacterial pathogens are subject to changes in environmental conditions such as nutrient availability, immune response challenges, bacterial density and physical ...contacts with targeted host cells. These conditions occur in the colonized organs, in diverse regions within infected tissues or even at the subcellular level for intracellular pathogens. Integration of environmental cues leads to measurable biological responses in the bacterium required for adaptation. Recent progress in technology enabled the study of bacterial adaptation in situ using genetically encoded reporters that allow single cell analysis or whole body imaging based on fluorescent proteins, alternative fluorescent assays or luciferases. This review presents a historical perspective and technical details on the methods used to develop transcriptional reporters, protein–protein interaction assays and secretion detection assays to study pathogenic bacteria adaptation in situ. Finally, studies published in the last 5years on gram positive and gram negative bacterial adaptation to the host during infection are discussed. However, the methods described here could easily be extended to study complex microbial communities within host tissue and in the environment.
This essay surveys the destruction of 631 African American schools during the Reconstruction era. Drawing from newspaper reports, congressional testimony, and the archives of the Freedmen's Bureau, ...it provides the most comprehensive account to date of violence against African American education in the postwar South. However, acknowledging that the total number of schools destroyed was probably far higher, the article also explores the forces that obscured evidence of attacks and precluded a more accurate count, particularly a lack of systematic attention to the issue in Freedmen's Bureau reports and the political machinations of congressional Democrats.
Tribolium castaneum and Rhyzopertha dominica are cosmopolitan, destructive postharvest pests. Although research has investigated how high densities of T. castaneum affect attraction to the ...aggregation pheromone by conspecifics, research into the behavioral response of both species to food cues after high density exposure has been lacking despite its importance to foraging ecology. Our goal was to manipulate and observe the effects of crowding on the behavioral response of both species to common food and pheromonal stimuli and to determine how the headspace emission patterns from grain differed under increasing densities. Densities of colonies for both species was altered (10-500 adults) on a fixed quantity of food (10 g of flour or whole wheat), then the behavioral response to common food and pheromonal cues was evaluated in a wind tunnel and release-recapture experiment, while volatiles were examined through gas chromatography coupled with mass spectrometry. Importantly, at least for T. castaneum, crowded conditions attenuate attraction to food-based stimuli, but not pheromonal stimuli. Crowding seemed to have no effect on R. dominica attraction to food and pheromonal stimuli in the wind tunnel, but exposure to high density cues did elicit 2.1-3.8-fold higher captures in traps. The relative composition and abundance of headspace volatiles emitted varied significantly with different densities of beetles and was also species-specific. Overall, our results have implications for expanding our understanding of the foraging ecology of two economically important pests.
ABSTRACT
The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular ...histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular Ca2+i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nacht‐, LRR‐, and PYD‐domains‐containing protein 3 (NLRP3) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in Ca2+i, as wellas defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction.—Kalbitz, M., Grailer, J. J., Fattahi, F., Jajou, L., Herron, T. J., Campbell, K. F., Zetoune, F. S., Bosmann, M., Sarma, J. V., Huber‐Lang, M., Gebhard, F., Loaiza, R., Valdivia, H. H., Jalife, J., Russell, M. W., Ward, P. A. Role of extracellular histones in the cardiomyopathy of sepsis. FASEB J. 29, 2185‐2193 (2015). www.fasebj.org
In operational data assimilation, observation errors are generally assumed to be uncorrelated, though some observations, such as satellite data, have correlated errors. We show that, if ...observation‐error correlations are correctly accounted for, an observing instrument with spatially correlated errors is better able to resolve small scales than an instrument with the same error variance and uncorrelated errors. We explore the disadvantages of falsely assuming uncorrelated observation errors, investigating two methods of compensating for such mis‐specification by either observation‐error inflation or data thinning. We identify scenarios in which correctly specifying the covariance reduces small‐scale error by over 99%.
Evaluating effectiveness of speech/phrase recognition software in critically ill patients with speech impairments.
Prospective study.
Tertiary hospital critical care unit in the northwest of England.
...14 patients with tracheostomies, 3 female and 11 male.
Evaluation of dynamic time warping (DTW) and deep neural networks (DNN) methods in a speech/phrase recognition application. Using speech/phrase recognition app for voice impaired (SRAVI), patients attempted mouthing various supported phrases with recordings evaluated by both DNN and DTW processing methods. Then, a trio of potential recognition phrases was displayed on the screen, ranked from first to third in order of likelihood.
A total of 616 patient recordings were taken with 516 phrase identifiable recordings. The overall results revealed a total recognition accuracy across all three ranks of 86% using the DNN method. The rank 1 recognition accuracy of the DNN method was 75%. The DTW method had a total recognition accuracy of 74%, with a rank 1 accuracy of 48%.
This feasibility evaluation of a novel speech/phrase recognition app using SRAVI demonstrated a good correlation between spoken phrases and app recognition. This suggests that speech/phrase recognition technology could be a therapeutic option to bridge the gap in communication in critically ill patients.
Communication can be attempted using visual charts, eye gaze boards, alphabet boards, speech/phrase reading, gestures and speaking valves in critically ill patients with speech impairments.
Deep neural networks and dynamic time warping methods can be used to analyse lip movements and identify intended phrases.
Our study shows that speech/phrase recognition software has a role to play in bridging the communication gap in speech impairment.
The number of subduction zones that facilitated the northward translation of the Anatolide‐Tauride continental terrane derived from Gondwana to the southern margin of Eurasia at the longitude of ...western Turkey is debated. We hypothesized that if two north dipping subduction zones facilitated incipient collision in western Turkey, a late Cretaceous arc would have formed within the Neotethys and along the southern margin of Eurasia. To determine if an island arc formed within the Neotethys we investigated the sedimentary record of the Central Sakarya basin, which was deposited along the southern margin of Eurasia from 85 to 45 million years ago. Detrital zircon deposited within the lower levels of the Central Sakarya basin (the Değirmenözü Formation) are associated with south to north‐directed paleocurrents and exhibit a unimodal late Cretaceous age peak sourced from isotopically juvenile mantle melts. Zircon maximum depositional ages from the Değirmenözü Formation cluster between 95 and 90 Ma and are 5–10 Myr older than biostratigraphic depositional ages. Between 95 and 80 Ma, a 12‐unit shift from mantle to crustal derived εHf values occurs in the overlying Yenipazar Formation. We explain the absence of Paleozoic, Eurasian‐sourced detrital zircon, the rapid shift from mantle to crustal derived εHf values, and lag time in terms of passive margin subduction within an isolated intra‐oceanic subduction zone, whose island arc was reworked from south to north into the Central Sakarya basin during incipient collision. Thus, widely outcropping late Cretaceous plutonic rocks within Eurasia must have belonged to an additional convergent margin.
Key Points
We leveraged the isotopic signature of subducted passive margin to test incipient collision models in northwest Turkey
Passive margin subduction resulted in the development of an isolated intra‐oceanic basin
Two north dipping subduction zones facilitated incipient collision in the region
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