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For around half of the couples who have trouble conceiving the cause of infertility is sperm-related. Intracytoplasmic sperm injection (ICSI) is the most common and successful treatment for male infertility. Here, the pioneers for the technique, along with authorities in the field, describe the underlying science of ICSI and other micromanipulation techniques. Practical advice for performing the techniques is covered in depth, including sperm selection, laser-assisted ICSI, and the use of piezo in ICSI. Examining the safety of ICSI in animal models as well as the impact of ICSI on the health and well-being of the children conceived through the procedure is discussed. This manual is an essential resource for clinical embryologists and laboratory personnel wishing to refine or develop techniques and improve outcomes.
This essential reference for students and scholars in the input-output research and applications community has been fully revised and updated to reflect important developments in the field. Expanded coverage includes construction and application of multiregional and interregional models, including international models and their application to global economic issues such as climate change and international trade; structural decomposition and path analysis; linkages and key sector identification and hypothetical extraction analysis; the connection of national income and product accounts to input-output accounts; supply and use tables for commodity-by-industry accounting and models; social accounting matrices; non-survey estimation techniques; and energy and environmental applications. Input-Output Analysis is an ideal introduction to the subject for advanced undergraduate and graduate students in many scholarly fields, including economics, regional science, regional economics, city, regional and urban planning, environmental planning, public policy analysis and public management.
Several recent reports have raised concern that infected coworkers may be an important source of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) acquisition by healthcare personnel. In a suspected outbreak among emergency department personnel, sequencing of SARS-CoV-2 confirmed transmission among coworkers. The suspected 6-person outbreak included 2 distinct transmission clusters and 1 unrelated infection.
Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.
We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.
Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).
In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.
The British Columbia Farmers’ Market Nutrition Coupon Program (FMNCP) provides low-income households with coupons valued at $21/week for 16 weeks to purchase healthy foods in farmers’ markets. Our objective was to explore FMNCP participants’ experiences of accessing nutritious foods, and perceived programme outcomes.
The current study used qualitative description methodology. Semi-structured interviews were conducted with FMNCP participants during the 2019 farmers' market season. Directed content analysis was used to analyse the data, whereby the five domains of Freedman et al.’s framework of nutritious food access provided the basis for an initial coding scheme. Data that did not fit within the framework’s domains were coded inductively.
One urban and two rural communities in British Columbia, Canada.
Twenty-eight adults who were participating in the FMNCP.
Three themes emerged: autonomy and dignity, social connections and community building, and environmental and programmatic constraints. Firstly, the programme promoted a sense of autonomy and dignity through financial support, increased access to high-quality produce, food-related education and skill development and mitigating stigma and shame. Secondly, shopping in farmers' markets increased social connections and fostered a sense of community. Finally, participants experienced limited food variety in rural farmers' markets, lack of transportation and challenges with redeeming coupons.
Participation in the FMNCP facilitated access to nutritious foods and enhanced participants’ diet quality, well-being and health. Strategies such as increasing the amount and duration of subsidies and expanding programmes may help improve participants’ experiences and outcomes of farmers' market food subsidy programmes.
Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.
Colleges and universities around the world engaged diverse strategies during the COVID-19 pandemic. Baylor University, a community of ˜22,700 individuals, was 1 of the institutions which resumed and sustained operations. The key strategy was establishment of multidisciplinary teams to develop mitigation strategies and priority areas for action. This population-based team approach along with implementation of a “Swiss Cheese” risk mitigation model allowed small clusters to be rapidly addressed through testing, surveillance, tracing, isolation, and quarantine. These efforts were supported by health protocols including face coverings, social distancing, and compliance monitoring. As a result, activities were sustained from August 1 to December 8, 2020. There were 62,970 COVID-19 tests conducted with 1435 people testing positive for a positivity rate of 2.28%. A total of 1670 COVID-19 cases were identified with 235 self-reports. The mean number of tests per week was 3500 with approximately 80 of these positive (11/d). More than 60 student tracers were trained with over 120 personnel available to contact trace, at a ratio of 1 per 400 university members. The successes and lessons learned provide a framework and pathway for similar institutions to mitigate the ongoing impacts of COVID-19 and sustain operations during a global pandemic.
ABSTRACT IMPACT: The pathophysiologic features of a metabolomic endotype that predicts patient outcomes due to sepsis have the potential to direct new therapies that target immune dysregulation and bioenergetic insufficiency. OBJECTIVES/GOALS: Acute respiratory failure (ARF) requiring mechanical ventilation is a frequent complication of sepsis and other disorders. It is associated with high morbidity and mortality. Despite its severity and prevalence, little is known about metabolic and bioenergetic changes that accompanying ARF. METHODS/STUDY POPULATION: In this study, semiquantitative and quantitative ultrahigh performance liquid chromatography mass spectrometry (UHPLC MS) analysis was performed on patient serum collected from the Trial with Acute Respiratory failure patients: evaluation of Global Exercise Therapies (TARGET). Serum from survivors (n=15) and nonsurvivors (n=15) was collected at day 1 and day 3 after admission to the medical intensive care unit as well as at discharge in survivors. Pathway analysis of the biochemical changes was performed to determine whether the disruption in specific metabolic pathways can identify the bioenergetic and metabolomic profile of these patients. RESULTS/ANTICIPATED RESULTS: Significant metabolomic differences were related to biosynthetic intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, and decreased acyl-glycerophosphocholines in nonsurvivors compared to survivors. The metabolites associated with poor outcomes are substrates of enzymatic processes dependent on NAD(P), while the abundance of NAD cofactors rely on the bioavailability of dietary vitamins B1, B2 and B6. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with an alteration of the glutathione-dependent drug metabolism as characterized by the substantial differences observed in the acetaminophen metabolome. DISCUSSION/SIGNIFICANCE OF FINDINGS: This metabolomic endotype represents a previously unappreciated association between severity of outcomes and micronutrient deficiency, thus pointing to new pharmacologic targets and highlighting the need for nutritional remediation upon hospitalization to improve patient outcomes due to ARF.
ABSTRACT IMPACT: This study provides insight into how MED2 impacts the immune cells surrounding glioblastoma that help it to grow and spread; having a more complete understanding of how MED2 works will help us better develop therapies that may one day enter the clinic to improve patient outcomes in glioblastoma. OBJECTIVES/GOALS: The purpose of this study was to determine whether the phosphorylation state of the MED2 peptide impacts its biological activity in GBM and macrophages. MED2 variants include the phosphorylatable wild-type (MED2), pseudo-phosphorylated (MED2-PP), non-phosphorylatable (MED2-NP) and control length (CTL2) peptides. METHODS/STUDY POPULATION: MED2, MED2-NP, MED2-PP, and CTL2 were screened against a panel of molecularly characterized glioblastoma patient derived xenografts and IL4/13 stimulated M2-like THP-1 macrophages. The luminescent cell viability assay, CellTiter-Glo, was used to determine viability. RESULTS/ANTICIPATED RESULTS: The proneural lines XD456 and X1441 were highly sensitive to 5 µM MED2 and 5 µM MED2NP compared to 5 µM MED2PP (p<0.001). There was no statistically significant difference between untreated, 5 µM CTL2, and 5 µM MED2PP groups or between the MED2NP and MED2 treated groups. M2-like THP-1 macrophages were highly sensitive to 10 µM MED2NP compared to 10 µM CTL2 (p<0.01) and 10 µM MED2PP (p<0.01) No statistically significant difference was observed between untreated, 10 µM MED2, 10 µM MED2PP, and 10 µM CTL2 groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The phosphorylation state of MED2 determines its toxicity. When MED2 is phosphorylated, it is nontoxic to GBM or M2-like macrophages. The non-phosphorylatable version is toxic to both GBM and M2-like macrophages. The wild-type peptide is toxic to GBM but not M2-like macrophages, suggesting that MED2 may be phosphorylated in M2-like macrophages.
Before coronavirus disease 2019 (COVID-19), few hospitals had fully tested emergency surge plans. Uncertainty in the timing and degree of surge complicates planning efforts, putting hospitals at risk of being overwhelmed. Many lack access to hospital-specific, data-driven projections of future patient demand to guide operational planning. Our hospital experienced one of the largest surges in New England. We developed statistical models to project hospitalizations during the first wave of the pandemic. We describe how we used these models to meet key planning objectives. To build the models successfully, we emphasize the criticality of having a team that combines data scientists with frontline operational and clinical leadership. While modeling was a cornerstone of our response, models currently available to most hospitals are built outside of their institution and are difficult to translate to their environment for operational planning. Creating data-driven, hospital-specific, and operationally relevant surge targets and activation triggers should be a major objective of all health systems.
We construct smooth, non-symmetric plasma equilibria which possess closed, nested flux surfaces and solve the magnetohydrostatic (steady three-dimensional incompressible Euler) equations with a small force. The solutions are also ‘nearly’ quasisymmetric. The primary idea is, given a desired quasisymmetry direction $\xi$, to change the smooth structure on space so that the vector field $\xi$ is Killing for the new metric and construct $\xi$–symmetric solutions of the magnetohydrostatic equations on that background by solving a generalized Grad–Shafranov equation. If $\xi$ is close to a symmetry of Euclidean space, then these are solutions on flat space up to a small forcing.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
Predictive adaptive responses (PARs) are a form of developmental plasticity in which the developmental response to an environmental cue experienced early in life is delayed and yet, at the same time, the induced phenotype anticipates (i.e., is completely developed before) exposure to the eventual environmental state predicted by the cue, in which the phenotype is adaptive. We model this sequence of events to discover, under various assumptions concerning the cost of development, what lengths of delay, developmental time, and anticipation are optimal. We find that in many scenarios modeled, development of the induced phenotype should be completed at the exact same time that the environmental exposure relevant to the induced phenotype begins: that is, in contrast to our observed cases of PARs, there should be no anticipation. Moreover, unless slow development is costly, development should commence immediately after the cue: there should be no delay. Thus, PARs, which normally have non-zero delays and/or anticipation, are highly unusual. Importantly, the exceptions to these predictions of zero delays and anticipation occurred when developmental time was fixed and delaying development was increasingly costly. We suggest, therefore, that PARs will only evolve under three kinds of circumstances: (i) there are strong timing constraints on the cue and the environmental status, (ii) delaying development is costly, and development time is either fixed or slow development is costly, or (iii) when the period between the cue and the eventual environmental change is variable and the cost of not completing development before the change is high. These predictions are empirically testable.
Summer monsoon rainfall is controlled by a number of factors but in general it is expected to intensify as the Earth becomes warmer. Rainfall is expected to be higher in South Asia, with the exception of Northwest India and Pakistan where drying is predicted. The Indian monsoon will be more prone to significant breaks. More cyclones are expected to make landfall in the Arabian Sea, while in East Asia typhoons will affect eastern China more. Rainfall is not expected to change greatly in China, but higher temperatures will result in more frequent drought especially in North China and the Tibetan Plateau where warming is strongest. Pollution will reduce rainfall, counteracting the effect of higher temperatures. Traditional small-scale farming is more effective at retaining soil moisture and may be more appropriate than large industrial agriculture in coping with the anticipated environmental changes. Sea-level rise is expected to rise approximately 36 cm by 2100, even assuming that CO2 emissions are capped. These rises are expected to more than double the occurrence of major tidal flooding, placing millions of people in jeopardy by the end of the century, especially in Bangladesh and Vietnam.
The Asian summer monsoon provides most of the moisture supply across Asia supporting large populations, controlling the natural vegetation and types of agriculture practiced. Colder conditions at the Glacial Maximum resulted in weaker summer precipitation, with the warmest, wettest conditions peaking around 6000–8000 years ago. We review how temperature, rainfall, changes in river load and course, and sea-level rise have intersected to create the unique agricultural landscape of Asia. Temperatures related to monsoonal pattern dictate the number of growing days for various critical crops, constraining where rice, millet, and wheat can be cultivated. The monsoon also provides water for the major rivers many of which originate in the Tibetan Plateau and which supply waters to the fertile floodplains across the region. Rapid glacial melting at 8200 years ago resulted a sharp drying of the climate in Asia lasting around 400 years. Rainfall particularly declined in peninsular India as well as in North China, now regions of dense population. This event can be used as an analog for potential future warming of the global climate into the twenty-first century.
The farmers who domesticated and grew rice throughout history developed expert knowledge that successfully allowed them to operate farming systems that are the most productive in terms of calories per hectare worldwide. Throughout both the historic and prehistoric record, Asian rice farmers have developed a dazzling array of techniques to deal with the climatic variations and changes in sea level and river evolution. Southern China is less impacted by changes in rainfall and precipitation than Northern China or South Asia. Humans have, however, constructed a unique niche for this aquatic plant, moving it into areas well outside of its natural range. This chapter outlines how humans first domesticated rice and controlled rivers and mastered the irrigation systems that support it.