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This paper provides a user’s guide to the general theory of approximate randomization tests developed in Canay, Romano, and Shaikh (2017a. “Randomization Tests under an Approximate Symmetry Assumption.” Econometrica 85 (3): 1013–30) when specialized to linear regressions with clustered data. An important feature of the methodology is that it applies to settings in which the number of clusters is small – even as small as five. We provide a step-by-step algorithmic description of how to implement the test and construct confidence intervals for the parameter of interest. In doing so, we additionally present three novel results concerning the methodology: we show that the method admits an equivalent implementation based on weighted scores; we show the test and confidence intervals are invariant to whether the test statistic is studentized or not; and we prove convexity of the confidence intervals for scalar parameters. We also articulate the main requirements underlying the test, emphasizing in particular common pitfalls that researchers may encounter. Finally, we illustrate the use of the methodology with two applications that further illuminate these points: one to a linear regression with clustered data based on Meng, Qian, and Yared (2015. “The Institutional Causes of china’s Great Famine, 1959–1961.” The Review of Economic Studies 82 (4): 1568–611) and a second to a linear regression with temporally dependent data based on Munyo and Rossi (2015. “First-day Criminal Recidivism.” Journal of Public Economics 124: 81–90). The companion Rand Statapackages facilitate the implementation of the methodology and the replication of the empirical exercises.

As the molecular mechanisms of biological aging become better understood, there is growing interest in identifying interventions that target those mechanisms to promote extended health and longevity. The budding yeast Saccharomyces cerevisiaehas served as a premier model organism for identifying genetic and molecular factors that modulate cellular aging and is a powerful system in which to evaluate candidate longevity interventions. Here we screened a collection of natural products and natural product mixtures for effects on the growth rate, mTOR-mediated growth inhibition, and replicative lifespan. No mTOR inhibitory activity was detected, but several of the treatments affected growth rate and lifespan. The strongest lifespan shortening effects were observed for green tea extract and berberine. The most robust lifespan extension was detected from an extract of Pterocarpus marsupiumand another mixture containing Pterocarpus marsupiumextract. These findings illustrate the utility of the yeast system for longevity intervention discovery and identify Pterocarpus marsupiumextract as a potentially fruitful longevity intervention for testing in higher eukaryotes.

Hydrogen (H2) has the potential to be a transformative technology as an enabler of a low-carbon future and a promoter of renewable energy. When H2is injected and stored in the subsurface, it has the potential to interact with the caprock (usually shale), which overlies and seals the storage reservoir. This study examines the geochemical reactions or changes in surface morphology of Eagle Ford Shale, a proxy for caprock, upon exposure to H2at 50 °C and 10.3 MPa. Exposures were also performed with N2to provide an experimental control. Scanning electron microscopy with energy dispersive spectroscopy, atomic force microscopy, and optical photothermal-infrared spectroscopy were applied to quantify surface changes on the microscale and nanoscale level. Fluid chemistry changes were monitored by ion chromatography and inductively coupled plasma mass spectrometry. Exposure of Eagle Ford Shale to H2gas alone did not result in any chemical alterations to the shale or any changes in the surface morphology. Exposure of Eagle Ford Shale to both H2and water as well as N2and water resulted in changes to the surface morphology because of gypsum dissolution and reprecipitation, thus indicating that H2is not necessary to promote changes. Pure pyrite was the most reactive with H2possibly resulting in a reduction to pyrrhotite. These initial studies suggest that the extent of reactions activated by hydrogen with caprock is minor under the temperature and pressure conditions that would represent underground hydrogen storage.

Introduction:The recently approved COVID-19 vaccine in 2021 provided a glimmer of hope to all people who had isolated, or lost loved ones to the SARS-COVID-19 virus. Clinics were rapidly established in non-traditional settings in order to meet the need in the early phases of the vaccination program. Contractor support provided rapid personnel support to meet the needs of many locations in several states. Consideration of basic infrastructure requirements such as Incident Command, security, HVAC, electricity, water and sanitation were part of a state supported vaccine clinic in an economically challenged neighborhood in downtown Miami, Florida.Method:Topics to be discussed include staffing mixes, language/cultural concerns, handheld EMR applications, patient flow, immunization practices, testing practices, vaccine security, adverse event management, infection control procedures and the ever present supply chain challenges. The discussion will be framed from the perspective of the Chief Nursing Officer in an ever challenging vaccine environment.Results:Over 20,000 vaccines were successfully provided in a little over three months, and a community-based Student Internship program was also implemented.Conclusion:Vaccine administration is possible in a variety of settings. Foundational principles of vaccine security, management of the environment and provision of safety and security for patients and staff will help to ensure a successful public health campaign.

Purpose: Within earned value management, the cost performance index (CPI) and the critical ratio (CR) are used to generate the estimates at completion (EACs). According to the research in the 1990s, estimating the final contract’s cost at completion (CAC) using EACCRis a quicker predictor of the actual final cost versus using EACCPI. This paper aims to investigate whether this trend stills holds for modern department of defense contracts. Design/methodology/approach: Accessing the Cost Assessment Data Enterprise (CADE) database, 451 contracts consisting of 863 contract line item numbers (CLINs) were initially retrieved and analyzed in three stages. The first replicated the work conducted in 1990s. The second stage entailed calculating 95 per cent confidence intervals and hypothesis tests regarding percentage accuracy of EACs for a contract’s final CAC. Lastly, regression analysis was conducted to characterize major, moderate and minor influencers on EAC reliability. Findings: For modern contracts, EACCRaligns more with EACCPIand no longer demonstrates early accuracy of a contract’s final CAC. Contract percentage completion strongly reduced the per cent error of estimating CAC, while cost-plus-fixed-fee contracts and those with no work breakdown structure greater than Level 2 negatively affected accuracy. Social implications: To militate against optimism of early assessment of a contract's true cost. Originality/value: This paper provides empirical evidence that EACCRbehaves more like EACCPIwith respect to modern contracts, suggesting that today’s contracts have relatively high SPI. Therefore, caution is warranted for program managers when estimating the CAC from contract initiation up to and slightly beyond the mid-point of completion.

Nitric acid, a well-known sink of NOxgases in the atmosphere, has been found to be photoactive while adsorbed on tropospheric particles. When adsorbed onto semiconductive metal oxides, nitrate’s photochemical degradation can be interpreted as a photocatalytic process. Yet, the photolysis of nitrate ions on the surface of aerosols can also be initiated by changes in the symmetry of the ion upon adsorption. In this study, we use quantum chemistry to model the vibrational spectra of adsorbed nitrate on TiO2, a semiconductor component of atmospheric aerosols, and determine the kinetics of the heterogeneous photochemical degradation of nitrate under simulated solar light. Frequencies and geometry calculations suggest that the symmetry of chemisorbed nitrate ion depends strongly on coadsorbed water, with water changing the reactive surface of TiO2. Upon irradiation, surface nitrate undergoes photolysis to yield nitrogen-containing gaseous products including NO2, NO, HONO, and N2O, in proportions that depend on relative humidity (RH). In addition, the heterogeneous photochemistry rate constant decreases an order of magnitude, from (5.7 ± 0.1) × 10–4s–1on a dry surface to (7.1 ± 0.8) × 10–5s–1when nitrate is coadsorbed with water above monolayer coverage. Little is known about the roles of coadsorbed water on the heterogeneous photochemistry of nitrates on TiO2, along with its impact on the chemical balance of the atmosphere. This work discusses the roles of water in the photolysis of surface nitrates on TiO2and the concomitant renoxification of the atmosphere.

The mechanistic target of rapamycin (mTOR) is a central regulator of growth and proliferation and mTOR inhibition is a promising therapy for a variety of diseases and disorders. Inhibition of mTOR complex I (mTORC1) with rapamycin delays aging and increases healthy longevity in laboratory animals and is used clinically at high doses to prevent organ transplant rejection and to treat some forms of cancer. Clinical use of rapamycin is associated with several unwanted side effects, however, and several strategies are being taken to identify mTORC1 inhibitors with fewer side effects. We describe here a yeast-based growth assay that can be used to screen for novel inhibitors of mTORC1. By testing compounds using a wild-type strain and isogenic cells lacking either TOR1or FPR1, we can resolve not only whether a compound is an inhibitor of mTORC1 but also whether the inhibitor acts through a mechanism similar to rapamycin by binding Fpr1. Using this assay, we show that rapamycin derivatives behave similarly to rapamycin, while caffeine and the ATP competitive inhibitors Torin 1 and GSK2126458 are mTORC1 inhibitors in yeast that act independently of Fpr1. Some mTOR inhibitors in mammalian cells do not inhibit mTORC1 in yeast, and several nutraceutical compounds were not found to specifically inhibit mTOR but resulted in a general inhibition of yeast growth. Our screening method holds promise as a means of effectively assaying drug libraries for mTOR-inhibitory molecules in vivo that may be adapted as novel treatments to fight diseases and extend healthy longevity.

The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods.

Many women with no history of executive dysfunction report difficulties in this domain during the menopause transition. Lisdexamfetamine (LDX) has been suggested to be a safe and effective treatment option for these women. However, the mechanism by which LDX improves executive functioning in these women is not known. Here we investigated the effects of LDX on brain activation and neurochemistry, hypothesizing that LDX would be associated with increased activation and decreased glutamate in executive regions. Fourteen women underwent multimodal neuroimaging at 7T at three time points in this baseline-corrected, double-blind, placebo-controlled, crossover study. Effects of LDX on symptom severity, blood-oxygen-level-dependent (BOLD) signal, and dorsolateral prefrontal cortex (DLPFC) glutamate+glutamine (Glx) were measured using a clinician-administered questionnaire, fMRI during performance of a fractal n-back task, and 1H-MRS, respectively. The effect of treatment (LDX minus baseline vs placebo minus baseline) on these behavioral and neural markers of executive function was examined using repeated measures mixed effects models. LDX treatment was associated with decreased symptom severity, increased activation in the insula and DLPFC, and decreased DLPFC Glx. In addition, the magnitude of LDX-induced improvement in symptom severity predicted both direction and magnitude of LDX-induced change in insular and DLPFC activation. Moreover, symptom severity was positively correlated with Glx concentration in the left DLPFC at baseline. These findings provide novel evidence that the neural mechanisms by which LDX acts to improve self-reported executive functioning in healthy menopausal women with midlife onset of executive difficulties include modulation of insular and DLPFC recruitment as well as decrease in DLPFC Glx concentration.

Patients transferred between hospitals are at high risk of adverse events and mortality. This study aims to identify which components of the transfer handoff process are important predictors of adverse events and mortality.

Health care emergency preparedness has undergone significant changes since the first widespread distribution of federal funds occurred in 2002. Prior to the development of the Health Resources and Service Administration Bioterrorism Preparedness grant, support to hospitals and public health was limited to smaller regional preparedness programs such as the Chemical Stockpile Emergency Preparedness Program. Measurable progress with both the hospital preparedness program and public health emergency preparedness requires development of partnerships, establishment of coalitions, development of measurable objectives, and a community willingness to work together to solve complex preparedness problems.

Fetal adrenal gland volumes on 3‐dimensional sonography have been studied as potential predictors of preterm birth. However, no consistent methodology has been published. This article describes the methodology used in a study that is evaluating the effects of maternal early life stress on fetal adrenal growth to allow other researchers to compare methodologies across studies. Fetal volumetric data were obtained in 36 women at 20 to 22 and 28 to 30 weeks' gestation. Two independent examiners measured multiple images of a single fetal adrenal gland from each sonogram. Intra‐ and inter‐rater consistency was examined. In addition, fetal adrenal volumes between male and female fetuses were reported. The intra‐ and inter‐rater reliability was satisfactory when the mean of 3 measurements from each rater was used. At 20 weeks' gestation, male fetuses had larger average adjusted adrenal volumes than female fetuses (mean, 0.897 versus 0.638; P= .004). At 28 weeks' gestation, the fetal weight was more influential in determining values for adjusted fetal adrenal volume (0.672 for male fetuses versus 0.526 for female fetuses; P= .034). This article presents a methodology for assessing fetal adrenal volume using 3‐dimensional sonography that can be used by other researchers to provide more consistency across studies.

Environmental contextIron, a limiting nutrient of plankton in the ocean, is deposited to the sea from atmospheric aerosols. In particular, atmospheric acidic conditions promote dissolution of iron from fly ash, a by-product of coal-fired power plants. Here, we report that the iron leached from fly ash depends on its source region, and that the type of combustion process may influence the iron species mobilized. AbstractFly ash, an iron-containing by-product of coal-fired power plants, has been observed in atmospheric aerosol plumes. Under the acidic atmospheric conditions resulting from the uptake of atmospheric gases, iron leached from fly ash can impact global biogeochemical cycles. However, the fly ash source region, as well as its generating power plant, plays an important role in the amount, speciation and lability of iron. Yet no comparative studies have been made on iron leached from fly ash from different sources. This study reports the iron mobilisation by proton-promoted dissolution from well-characterised fly ash samples from three distinctive locations: the USA Midwest, north-east India and Europe. In addition, pH dependency was also investigated. Proton-promoted dissolution showed a variability between source regions with a relative iron leach in the order USA Midwestern>north-east Indian>European ash. In addition, the initial rate of iron leach suggests that source region is indeed a determining factor in the iron leaching capacity of fly ash, because dissolution from Midwestern fly ash is also faster than both European and Indian ash. Finally, the combustion process of fly ash proved to be significant for the iron speciation, given that well-combusted fly ash samples leached mostly Fe3+ rather than bioavailable Fe2+. The role of fly ash should therefore be taken into account in order to better understand the effects of combustion particles in atmospheric iron deposition.

We evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant – a neurokinin 1 receptor antagonist.

Introduction:Postpartum depression (PPD) is a common and serious illness that affects up to 14% of women in the first month after childbirth. We present an update on the pharmacologic treatment of PPD, although there continues to be a lack of large, randomized controlled trials (RCTs).Areas covered:A review of the literature on the use of antidepressants, hormonal supplements and omega-3 fatty acids for the prevention and the treatment of PPD published since the original review in 2009 and the authors' opinion on the current status of the pharmacological treatment of PPD are covered. An electronic search was performed by using PubMed, Medline and PsychINFO. Inclusion criteria were: i) empirical articles in peer-reviewed English-language journals; ii) well-validated measures of depression; and iii) a uniform scoring system for depression among the sample.Expert opinion:Since the last Expert Opinion review, four antidepressant treatment studies and one prevention study of PPD have been published. Six RCTs evaluating the use of omega-3 fatty acids (four for prevention and two for treatment) have been published. There continues to be lack of data regarding the pharmacotherapy of PPD. However, serotonin reuptake inhibitors should be considered first-line for women with PPD after it has been determined that the proper diagnosis is not bipolar disorder. It is important to individualize treatment for women with PPD and consider the risks and benefits of treatment while breastfeeding.

Most studies of HLA sensitization after red blood cell transfusion in transplant candidates were done before widespread use of leukoreduced blood and based on relatively insensitive, nonspecific antibody assays. We evaluated the effect of transfusion on the breadth and magnitude of HLA antibody formation using current, sensitive, HLA-specific immunoassays.

Objectives. We identified academic training courses or topics most important to the careers of U.S. public health, environmental, and agricultural laboratory (PHEAL) scientist-managers and directors, and determined what portions of the national PHEAL workforce completed these courses.Methods. We conducted electronic national surveys in 2006 and 2011, and analyzed data using numerical ranking, Chi-square tests comparing rates, and Spearman's formula measuring rank correlation.Results. In 2006, 40 of 50 PHEAL directors identified 56 course topics as either important, useful, or not needed for someone in their position. These course topics were then ranked to provide a list of 31 core courses. In 2011, 1,659 of approximately 5,555 PHEAL scientific and technical staff, using a subset of 25 core courses, evidenced higher core course completion rates associated with higher-level job classification, advanced academic degree, and age. The 2011 survey showed that 287 PHEAL scientist-managers and directors, on average, completed 37.7% (n=5/13) of leadership/managerial core courses and 51.7% (n=6/12) of scientific core courses. For 1,659 laboratorians in all scientific and technical classifications, core-subject completion rates were higher in local laboratories (42.8%, n=11/25) than in state (36.0%, n=9/25), federal (34.4%, n=9/25), and university (31.2%, n=8/25) laboratories.Conclusions. There is a definable range of scientific, leadership, and managerial core courses needed by PHEAL scientist-managers and directors to function effectively in their positions. Potential PHEAL scientist-managers and directors need greater and continuing access to these courses, and academic and practice entities supporting development of this workforce should adopt curricula and core competencies aligned with these course topics.

ABSTRACTObjective:To document the ability of public health laboratories to respond to radiological emergencies.Methods:The Association of Public Health Laboratories developed, distributed, and analyzed two separate surveys of public health laboratories representing the 50 US states and major nonstate jurisdictions. The 2009 All-Hazards Laboratory Preparedness Survey examined overall laboratory capability and capacity, with a subset of questions on radiation preparedness. A 2011 survey focused exclusively on radiation readiness.Results:The 50 state and District of Columbia public health laboratories responded to the 2009 All-Hazards Laboratory Preparedness Survey, representing a 98% response rate. In addition to the above laboratories, environmental and agricultural laboratories responded to the 2011 Radiation Capabilities Survey, representing a 76% response rate. Twenty-seven percent of the All-Hazards Survey respondents reported the ability to measure radionuclides in clinical specimens; 6% reported that another state agency or department accepted and analyzed these samples via a radioanalytical method. Of the Radiation Capabilities Survey respondents, 60% reported the ability to test environmental samples, such as air, soil, or surface water, for radiation; 48% reported the ability to test nonmilk food samples; 47% reported the ability to test milk; and 56% reported sending data for drinking water to the Environmental Protection Agency.Conclusions:Survey data reveal serious gaps in US radiological preparedness. In 2007, federal experts estimated it would take more than 4 years to screen 100 000 individuals for radiation exposure and 6 years to test environmental samples from a large-scale radiological emergency, relying on existing laboratory assets. Although some progress has been made since 2007, public health laboratory radiological test capabilities and capacities remain insufficient to respond to a major event. Adequate preparation requires significant new investment to build and enhance laboratory emergency response networks, as well as investments in the broader public health system in which public health laboratories function.(Disaster Med Public Health Preparedness. 2011;5:213-217)

This article reviews the literature on the use of antidepressants for symptoms associated with perimenopause. In some perimenopausal women, mood instability, insomnia and vasomotor symptoms cause significant distress. Studies of antidepressants for perimenopausal symptoms are summarized, with a focus on perimenopausal depression and vasomotor symptoms. Antidepressants should be considered as an alternative to hormone therapy for perimenopausal depression and hot flashes, especially when hormone therapy is contraindicated, or as an augmentation strategy for women who are only partially responsive to hormone therapy.

This article reviews the literature on the use of antidepressants for symptoms associated with perimenopause. In some perimenopausal women, mood instability, insomnia and vasomotor symptoms cause significant distress. Studies of antidepressants for perimenopausal symptoms are summarized, with a focus on perimenopausal depression and vasomotor symptoms. Antidepressants should be considered as an alternative to hormone therapy for perimenopausal depression and hot flashes, especially when hormone therapy is contraindicated, or as an augmentation strategy for women who are only partially responsive to hormone therapy.

Modafinil is a novel wake-promoting agent approved for the treatment of excessive sleepiness associated with narcolepsy that holds significant promise as an alternative treatment to traditional psychostimulants for excessive fatigue associated with medical and psychiatric disorders and as augmentation medication for treatment-resistant depression.

Recent changes in the Joint Commission Accrediting Hospital Organization (JCAHO) Environment of Care standards are forcing hospitals to revisit their disaster planning process. Emergency Management, a process that is familiar to municipal and industry planners is now part of hospital disaster planning. A framework for making the necessary changes to the hospital disaster plan is presented. Examples of tools that might be useful in the planning process are also included.

Patients with chronic ataxia resulting from traumatic central nervous system (CNS) damage frequently attain a gait pattern dependent upon upper extremity weight-bearing (UEWB). Traditional attempts to train these patients may perpetuate UEWB dependency, by not allowing optimal facilitation of balance and associated movement control required for independent ambulation. In the present study an ambulation retraining approach designed to facilitate coordination and balance while minimizing UEWB was used. This approach can allow the patient to train outside of the clinic; only about 5% of the actual therapy hours involved a therapist.

Electroconvulsive therapy (ECT) is recommended by the American Psychiatric Association Task Force on ECT as a safe and effective treatment of depression throughout pregnancy. We report here administration of ECT in the third trimester of pregnancy in a 33-year-old patient with severe bipolar depression.

Using a nonclinical, noncollege sample, this study set out to confirm and extend previous findings of a relationship between the cognitive-perceptual features of schizotypal personality and mixed handedness using the Schizotypal Personality Questionnaire (SPQ). Based on previous findings of relationships between nondextrality and thought disorder in schizophrenia, it was predicted that the odd speech subscale of the SPQ would have the strongest relationship with mixed handedness. Mixed-handed adults did have significantly higher scores than right-handed and left-handed adults on the cognitive-perceptual factor and its subscale of odd speech. Similar trends were also observed for the cognitive-perceptual subscales of suspiciousness, eccentric behavior, and unusual perceptual experiences. These results support and extend previous findings, and are broadly consistent with the association between thought disorder and nondextrality in schizophrenia.

The author presents her observations on the difference of Korea's public high schools from those in the U.S. She noticed several differences with respect to the physical appearance of students in Korea, including the girl's uniform. The set-up of the classes in Korean public high school is also different from America's, says the author.