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This article analyzes the theoretical properties of the hybrid test for superior predictive ability. A simple example reveals that the test may not be size-controlled at common significance levels with rejection rates exceeding $11\%$ at a $5\%$ nominal level. Generalizing this observation, the main results show the pointwise asymptotic invalidity of the hybrid test under reasonable conditions. Monte Carlo simulations support these theoretical findings.

Minerals in groundwater interact with various chemical and biological species including organic matter, proteins, and prevalent oxyanions, resulting in surface coatings and thin films of these different components.

The effects of atmospheric aging on single-particle nascent sea spray aerosol (nSSA) physicochemical properties, such as morphology, composition, phase state, and water uptake, are important to understanding their impacts on the Earth's climate. The present study investigates these properties by focusing on the aged SSA (size range of 0.1-0.6 μm) and comparing with a similar size range nSSA, both generated at a peak of a phytoplankton bloom during a mesocosm study. The aged SSAs were generated by exposing nSSA to OH radicals with exposures equivalent to 4-5 days of atmospheric aging. Complementary filter-based thermal optical analysis, atomic force microscopy (AFM), and AFM photothermal infrared spectroscopy were utilized. Both nSSA and aged SSA showed an increase in the organic mass fraction with decreasing particle sizes. In addition, aging results in a further increase of the organic mass fraction, which can be attributed to new particle formation and oxidation of volatile organic compounds followed by condensation on pre-existing particles. The results are consistent with single-particle measurements that showed a relative increase in the abundance of aged SSA core-shells with significantly higher organic coating thickness, relative to nSSA. Increased hygroscopicity was observed for aged SSA core-shells, which had more oxygenated organic species. Rounded nSSA and aged SSA had similar hygroscopicity and no apparent changes in the composition. The observed changes in aged SSA physicochemical properties showed a significant size-dependence and particle-to-particle variability. Overall, results showed that the atmospheric aging can significantly influence the nSSA physicochemical properties, thus altering the SSA effects on the climate.

We conducted an exploratory study to describe the emotional experience of adults aged 60 and older in the United States practicing social distancing during COVID-19. The survey asked respondents how they were feeling during social distancing. Responses (n=673) were coded into segments by affect and then specific emotional states. A large portion of respondents reported negative emotions (e.g. anxiety, loneliness). A smaller portion reported positive emotions (e.g. optimism, gratitude). Younger respondents (aged 60-70) reported more feelings of anxiousness and fear compared to older respondents (71+). Older respondents were more likely to report negative feelings towards the government. For both age groups, female respondents were significantly more likely to report feeling afraid and having negative feelings about their own health. We conclude that many older adults are vulnerable to negative emotional outcomes during the pandemic. This highlights the importance of interventions targeting vulnerable older adults.

Supplemental Methods and References. Description of additional methods and procedures used in the study. Also includes Supplemental References.

Upregulation of matrix metalloproteinase MMP-14 (MT1-MMP) is associated with poor prognosis in cancer patients, but it is unclear how MMP-14 becomes elevated in tumors. Here, we show that miR-181a-5p is downregulated in aggressive human breast and colon cancers where its levels correlate inversely with MMP-14 expression. In clinical specimens, enhanced expression of MMP-14 was observed in cancer cells located at the invasive front of tumors where miR-181a-5p was downregulated relative to adjacent normal cells. Bioinformatics analyses defined a potential miR-181a-5p response element within the 3′-untranslated region of MMP-14 that was validated in reporter gene experiments. Ectopic miR-181a-5p reduced MMP-14 expression, whereas miR-181a-5p attenuation elevated MMP-14 expression. In support of a critical relationship between these two genes, miR-181a-5p–mediated reduction of MMP-14 levels was sufficient to decrease cancer cell migration, invasion, and activation of pro-MMP-2. Furthermore, this reduction in MMP-14 levels was sufficient to reduce in vivo invasion and angiogenesis in chick chorioallantoic membrane assays. Taken together, our results establish the regulation of MMP-14 in cancers by miR-181a-5p through a posttranscriptional mechanism, and they further suggest strategies to elevate miR-181a-5p to prevent cancer metastasis. Cancer Res; 75(13); 2674–85. ©2015 AACR.

Initial COVID-19 pandemic research suggests that during the first few weeks of the pandemic women were disproportionately impacted by restrictions compared to men. This study explored whether these gender differences in coping with pandemic restrictions were present among older adults 8-9 months into the COVID-19 pandemic. Data are based on online survey responses (

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 cerevisiae has 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 marsupium and another mixture containing Pterocarpus marsupium extract. These findings illustrate the utility of the yeast system for longevity intervention discovery and identify Pterocarpus marsupium extract as a potentially fruitful longevity intervention for testing in higher eukaryotes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00418-x.

Minimum wage is used as a support for low-wage workers, but it is expected to increase unemployment and cause deterioration of the welfare of the unemployed. While earlier studies identify negative side effects of minimum wage, that may not be the case in the Philippines, where many workers migrate and send home large remittances. This study uses a computable general equilibrium model to examine the impacts of an increase in the domestic minimum wage on unemployment, migration, and output, as well as on welfare and inequality, in the Philippines. Our simulation results show that a minimum wage increase would indeed reduce domestic labor demand and prompt many unemployed workers to migrate out, leaving relatively few unemployed at home. While an increased volume of remittances would improve household welfare, it would also have some unintended effects, such as currency appreciation; decreased domestic production in labor-intensive and export-oriented industries; greater income disparity; and tax base erosion., The authors gratefully acknowledge the financial support of JSPS KAKENHI (No. 19K01622). The usual disclaimers apply, https://www.grips.ac.jp/list/jp/facultyinfo/hosoe_nobuhiro/

Oligodendrocytes exist in a heterogenous state and are implicated in multiple neuropsychiatric diseases including dementia. Cortical oligodendrocytes are a glial population uniquely positioned to play a key role in neurodegeneration by synchronizing circuit connectivity but molecular pathways specific to this role are lacking. We utilized oligodendrocyte-specific translating ribosome affinity purification and RNA-seq (TRAP-seq) to transcriptionally profile adult mature oligodendrocytes from different regions of the central nervous system. Weighted gene co-expression network analysis reveals distinct region-specific gene networks. Two of these mature myelinating oligodendrocyte gene networks uniquely define cortical oligodendrocytes and differentially regulate cortical myelination (M8) and synaptic signaling (M4). These two cortical oligodendrocyte gene networks are enriched for genes associated with dementia including MAPT and include multiple gene targets of the regulatory microRNA, miR-142-3p. Using a combination of TRAP-qPCR, miR-142-3p overexpression in vitro, and miR-142-null mice, we show that miR-142-3p negatively regulates cortical myelination. In rTg4510 tau-overexpressing mice, cortical myelination is compromised, and tau-mediated neurodegeneration is associated with gene co-expression networks that recapitulate both the M8 and M4 cortical oligodendrocyte gene networks identified from normal cortex. We further demonstrate overlapping gene networks in mature oligodendrocytes present in normal cortex, rTg4510 and miR-142-null mice, and existing datasets from human tauopathies to provide evidence for a critical role of miR-142-3p-regulated cortical myelination and oligodendrocyte-mediated synaptic signaling in neurodegeneration.

Women with a history of adverse childhood experiences (ACEs) enter pregnancy and the postpartum with a physiologic system programmed by early life stress, potentially reflected in psychophysiologic reactivity.We enrolled pregnant, psychiatrically healthy women ≥18 years old. Using the ACE Questionnaire, women were categorized as high (≥2 ACEs; n = 77) or low ACE (2 ACEs; n = 72). Participants completed an affective modulation of acoustic startle response (ASR) task during pregnancy and postpartum, in which ASR magnitude was measured while participants viewed pleasant, unpleasant, and neutral pictures. Two types of control trials were included (habituation trials presented at baseline and intertrial interval trials presented when no picture was present).Among high ACE women, ASR was significantly higher postpartum compared with pregnancy in the unpleasant (p = 0.002, β = 0.46, 95% CI [0.18, 0.74], χPhysiological reactivity increased in high ACE women from pregnancy to postpartum, but no change was observed in low ACE women.

BackgroundReflex Cryptococcal antigen (CrAg) testing in HIV-positive patients is done routinely at 47 laboratories in South Africa on samples with a confirmed CD4 count ObjectiveThis study aimed to verify the diagnostic performance of newer CrAg LFA assays against the predicate method.MethodsRemnant CD4 samples collected between February and June 2019, with confirmed predicate LFA CrAg results, were retested on settled plasma with the (i) IMMY CrAg semi-quantitative (SQ) LFA; (ii) Bio-Rad RDT CryptoPS SQ; and (iii) Dynamiker CrAg SQ assays, within 24 hours of predicate testing. Sensitivity/ specificity analyses were conducted comparing predicate versus the newer assays, with McNemar’s test’s p-values reported for comparative results (p values ResultsOf the 254 samples tested, 228 had comparative CrAg results across all assays. The predicate method reported 85 CrAg positive (37.2%), compared to between 35.08 and 37.28% for the Bio-Rad, IMMY SQ and Dynamiker assays. The IMMY CrAg SQ grading (+1 to +5) showed 67% of CrAg positive results had a grading ≥3, indicative of higher CrAg concentration (infection severity). False-negative results across all assays were 95% for all. False-positive results were highest for the Dynamiker LFA (14%) with a specificity of 77% (p=0.001). IMMY SQ and Bio-Rad assays specificities exceeded 90% (p=0.6 and 0.12). Internal quality control showed 100% accuracy for all assays.ConclusionPerformance verification of newer CrAg LFA assays under typical laboratory conditions varied, with best results by IMMY SQ and Bio-Rad. The high burden of HIV and cryptococcal disease in South Africa requires high specificity and - sensitivity (>90%) to prevent unnecessary treatment/hospitalization. The added value of positivity grading for patient management needs confirmation.

Atmospheric combustion particles, such as fly ash emitted from coal-fired power plants, are a potential source of atmospheric iron, with significant implications in climate and global biogeochemica...

Indoor surfaces are extremely diverse and their interactions with airborne compounds and aerosols influence the lifetime and reactivity of indoor emissions. Direct measurements of the physical and chemical state of these surfaces provide insights into the underlying physical and chemical processes involving surface adsorption, surface partitioning and particle deposition. Window glass, a ubiquitous indoor surface, was placed vertically during indoor activities throughout the House Observations of Microbial and Environmental Chemistry (HOMEChem) campaign and then analyzed to measure changes in surface morphology and surface composition. Atomic force microscopy-infrared (AFM-IR) spectroscopic analyses reveal that deposition of submicron particles from cooking events is a contributor to modifying the chemical and physical state of glass surfaces. These results demonstrate that the deposition of glass surfaces can be an important sink for organic rich particles material indoors. These findings also show that particle deposition contributes enough organic matter from a single day of exposure equivalent to a uniform film up to two nanometers in thickness, and that the chemical distinctness of different indoor activities is reflective of the chemical and morphological changes seen in these indoor surfaces. Comparison of the experimental results to physical deposition models shows variable agreement, suggesting that processes not captured in physical deposition models may play a role in the sticking of particles on indoor surfaces.

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 R and Stata packages facilitate the implementation of the methodology and the replication of the empirical exercises.

The cell wall of Clavibacter michiganensis subsp. michiganensis VKM Ас-1403Т (family Microbacteriaceae, class Actinobacteria) contains two polysaccharides. The first one is neutral (1 → 6) linked galactofuranan in which every second galactofuranose residue in the main chain substituted at position 3 by side trisaccharide, β-D-GlcpNAc-(1 → 3)-α-L-Rhap-(1 → 2)-α-D-Fucp-(1 →. The second polymer is pyruvylated galactomannan with the repeating unit, →3)-α-D-Galp-(1 → 3)-α-D-[4,6-S-Pyr]-Manp-(1 → 3)-α-D-Manp-(1 →. The cell wall glycopolymer structures were established by chemical and NMR spectroscopic methods. The obtained results provide new data on the cell wall composition of plant pathogenic species of the genus Clavibacter and can promote understanding the molecular mechanisms involved in colonization and infection of plants.

Background Deep transcranial magnetic stimulation (dTMS) with the H7-coil was FDA cleared for obsessive-compulsive disorder (OCD) in August 2018 based on multicenter sham-controlled studies. Here we look at the efficacy of dTMS for OCD in real world practices. Methods All dTMS clinics were asked to supply their data on treatment details and outcome measures. The primary outcome measure was response, defined by at least a 30% reduction in the Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline to endpoint. Secondary outcome measures included first response, defined as the first time the YBOCS score has met response criteria, and at least one-month sustained response. Analyses included response rate at the endpoint (after 29 dTMS sessions), number of sessions and days required to reach first response and sustained response. Results Twenty-two clinical sites with H7-coils provided data on details of treatment and outcome (YBOCS) measures from a total of 219 patients. One-hundred-sixty-seven patients who had at least one post-baseline YBOCS measure were included in the main analyses. Overall first and sustained response rates were 72.6% and 52.4%, respectively. The response rate was 57.9% in patients who had YBOCS scores after 29 dTMS sessions. First response was achieved in average after 18.5 sessions (SD = 9.4) or 31.6 days (SD = 25.2). Onset of sustained one-month response was achieved in average after 20 sessions (SD = 9.8) or 32.1 days (SD = 20.5). Average YBOCS scores demonstrated continuous reduction with increasing numbers of dTMS sessions. Conclusions In real-world clinical practice, the majority of OCD patients benefitted from dTMS, and the onset of improvement usually occurs within 20 sessions. Extending the treatment course beyond 29 sessions results in continued reduction of OCD symptoms, raising the prospect of value for extended treatment protocols in non-responders.

Nitric acid, a well-known sink of NO x gases 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) × 10-4 s-1 on a dry surface to (7.1 ± 0.8) × 10-5 s-1 when 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 TiO2 and the concomitant renoxification of the atmosphere.

Studies conducted at the beginning of Covid-19 precautions suggested that older adults were stressed, but hopeful. Less is known how coping has changed for older adults after experiencing months-long pandemic precautions. We explore differences in coping between the initial pandemic declaration in March 2020, and 9 months later, via an internet survey fielded in November 2020 (n= 781). We present summary data, using chi-square tests for subgroup analyses. A majority of respondents (aged M=66 yrs, range 60-89) were women (64%) and White (94%). When asked to compare their feelings to the beginning of the pandemic, 44.8% were more frustrated, 38.7% were more stressed, and 32.7% were more anxious. However, 38.3% were more appreciative. Women were significantly more likely than men to report increases in feeling frustrated, angry, scared, stressed, sad, and hopeless. Introverts were significantly more likely than extroverts to report an increase in loneliness and stress. Since the first few weeks of the pandemic, respondents reported more communication through video calls (45.2%), texting (40.2%), and phone calls (28.8%). Additionally, 61.5% spent more time on computers/tablets, 47.2% spent more time watching TV, and 24.5% spent more time praying. Extroverts were significantly more likely than introverts to report an increase in time with TV, phones, and computers/tablets. Women were significantly more likely than men to report increased texting and praying. These data provide further understanding of the impact of long-term pandemic precautions on older adults and suggest particular subgroups of older adults may benefit from public health and mental health interventions.

The cell wall glycopolymer structures of plant-associated strains Clavibacter sp. VKM Ac-1371, Clavibacter sp. VKM Ac-1372 and Clavibacter sp. VKM Ac-1374, members of three putative new species (family Microbacteriaceae, class Actinobacteria) were studied. Each strain was found to contain two glycopolymers, neutral and acidic ones. The main chain of neutral polymer, identical in all three strains, is (1 → 6)-linked β- d -galactofuranan with every second galactofuranose residue substituted at position 2 by side disaccharide, α- d -Manp-(1 → 2)-α- d -Ribf-(1 → . The second, acidic polymer, is pyruvate-containing galactomannan with the repeating unit, →3)-α- d -Galp-(1 → 3)-α- d -[4,6-S-Pyr]-Manp-(1 → 3)-α- d -Manp-(1 → . Reducing mannopyranose residues of the acidic polysaccharides repeating unit from strains VKM Ac-1372 and VKM Ac-1374 bear O-acetyl residues additionally. The cell wall glycopolymer structures were established by chemical and NMR spectroscopic methods with using one- and two-dimensional techniques 1H,1H COSY, TOCSY, ROESY and 1H,13C HSQC, HMBC. The results obtained provide new data on diversity of the bacterial cell wall glycopolymers and may prove valuable for microbial taxonomy and insight into the molecular mechanisms of interactions between bacteria and plants and also of bacterial adaptation to survival in desert systems.