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New cryogenic characterization techniques for exploring the nanoscale structure and chemistry of intact solid–liquid interfaces have recently been developed. These techniques provide high-resolution information about buried interfaces from large samples or devices that cannot be obtained by other means. These advancements were enabled by the development of instrumentation for cryogenic focused ion beam liftout, which allows intact solid–liquid interfaces to be extracted from large samples and thinned to electron-transparent thicknesses for characterization by cryogenic scanning transmission electron microscopy or atom probe tomography. Future implementation of these techniques will complement current strides in imaging of materials in fluid environments by in situ liquid-phase electron microscopy, providing a more complete understanding of the morphology, surface chemistry, and dynamic processes that occur at solid–liquid interfaces.
Psychotherapies for depression are equally effective on average, but individual responses vary widely. Outcomes can be improved by optimizing treatment selection using multivariate prediction models. A promising approach is the Personalized Advantage Index (PAI) that predicts the optimal treatment for a given individual and the magnitude of the advantage. The current study aimed to extend the PAI to long-term depression outcomes after acute-phase psychotherapy.
Data come from a randomized trial comparing cognitive therapy (CT, n = 76) and interpersonal psychotherapy (IPT, n = 75) for major depressive disorder (MDD). Primary outcome was depression severity, as assessed by the BDI-II, during 17-month follow-up. First, predictors and moderators were selected from 38 pre-treatment variables using a two-step machine learning approach. Second, predictors and moderators were combined into a final model, from which PAI predictions were computed with cross-validation. Long-term PAI predictions were then compared to actual follow-up outcomes and post-treatment PAI predictions.
One predictor (parental alcohol abuse) and two moderators (recent life events; childhood maltreatment) were identified. Individuals assigned to their PAI-indicated treatment had lower follow-up depression severity compared to those assigned to their PAI-non-indicated treatment. This difference was significant in two subsets of the overall sample: those whose PAI score was in the upper 60%, and those whose PAI indicated CT, irrespective of magnitude. Long-term predictions did not overlap substantially with predictions for acute benefit.
If replicated, long-term PAI predictions could enhance precision medicine by selecting the optimal treatment for a given depressed individual over the long term.
Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.
Design, setting, participants, and measurements:
We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.
Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.
These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).
To detect modest associations of dietary intake with disease risk, observational studies need to be large and control for moderate measurement errors. The reproducibility of dietary intakes of macronutrients, food groups and dietary patterns (vegetarian and Mediterranean) was assessed in adults in the UK Biobank study on up to five occasions using a web-based 24-h dietary assessment (n 211 050), and using short FFQ recorded at baseline (n 502 655) and after 4 years (n 20 346). When the means of two 24-h assessments were used, the intra-class correlation coefficients (ICC) for macronutrients varied from 0·63 for alcohol to 0·36 for polyunsaturated fat. The ICC for food groups also varied from 0·68 for fruit to 0·18 for fish. The ICC for the FFQ varied from 0·66 for meat and fruit to 0·48 for bread and cereals. The reproducibility was higher for vegetarian status (κ > 0·80) than for the Mediterranean dietary pattern (ICC = 0·45). Overall, the reproducibility of pairs of 24-h dietary assessments and single FFQ used in the UK Biobank were comparable with results of previous prospective studies using conventional methods. Analyses of diet–disease relationships need to correct for both measurement error and within-person variability in dietary intake in order to reliably assess any such associations with disease in the UK Biobank.
Research participants want to receive results from studies in which they participate. However, health researchers rarely share the results of their studies beyond scientific publication. Little is known about the barriers researchers face in returning study results to participants.
Using a mixed-methods design, health researchers (N = 414) from more than 40 US universities were asked about barriers to providing results to participants. Respondents were recruited from universities with Clinical and Translational Science Award programs and Prevention Research Centers.
Respondents reported the percent of their research where they experienced each of the four barriers to disseminating results to participants: logistical/methodological, financial, systems, and regulatory. A fifth barrier, investigator capacity, emerged from data analysis. Training for research faculty and staff, promotion and tenure incentives, and funding agencies supporting dissemination of results to participants were solutions offered to overcoming barriers.
Study findings add to literature on research dissemination by documenting health researchers’ perceived barriers to sharing study results with participants. Implications for policy and practice suggest that additional resources and training could help reduce dissemination barriers and increase the return of results to participants.
Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos.
Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders.
In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02).
It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.
Analysis of a recent surge of Morsnevbreen, Svalbard, is used to test predictions of the enthalpy balance theory of surging. High-resolution time series of velocities, ice thickness and crevasse distribution allow key elements of the enthalpy (internal energy) budget to be quantified for different stages of the surge cycle. During quiescence (1936–1990), velocities were very low, and geothermal heat slowly built-up enthalpy at the bed. Measurable mass transfer and frictional heating began in 1990–2010, then positive frictional heating-velocity feedbacks caused gradual acceleration from 2010 to 2015. Rapid acceleration occurred in summer 2016, when extensive crevassing and positive air temperatures allowed significant surface to bed drainage. The surge front reached the terminus in October 2016, coincident with a drop in velocities. Ice plumes in the fjord are interpreted as discharge of large volumes of supercooled water from the bed. Surge termination was prolonged, however, indicating persistence of an inefficient drainage system. The observations closely match predictions of the theory, particularly build-up of enthalpy from geothermal and frictional heat, and surface meltwater, and the concomitant changes in ice-surface elevation and velocity. Additional characteristics of the surge reflect spatial processes not represented in the model, but can be explained with respect to enthalpy gradients.
The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply.
To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid.
A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study.
Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes.
The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Replicate radiocarbon (14C) measurements of organic and inorganic control samples, with known Fraction Modern values in the range Fm = 0–1.5 and mass range 6 μg–2 mg carbon, are used to determine both the mass and radiocarbon content of the blank carbon introduced during sample processing and measurement in our laboratory. These data are used to model, separately for organic and inorganic samples, the blank contribution and subsequently “blank correct” measured unknowns in the mass range 25–100 μg. Data, formulas, and an assessment of the precision and accuracy of the blank correction are presented.
Excess energy intake is recognised as a strong contributing factor to the global rise of being overweight and obese. The aim of this paper was to investigate if oral sensitivity to complex carbohydrate relates to ad libitum consumption of complex carbohydrate foods in a sample group of female adults. Participants’ ((n 51 females): age 23·0 (sd 0·6) years (range 20·0–41·0 years); excluding restrained eaters) sensitivity towards maltodextrin (oral complex carbohydrate) and glucose (sweet taste) was assessed by measuring detection threshold (DT) and suprathreshold intensity perception (ST). A crossover design was used to assess consumption of two different iso-energetic preload milkshakes and ad libitum milkshakes – (1) glucose-based milkshake, (2) maltodextrin-based milkshake. Ad libitum intake (primary outcome) and eating rate, liking, hunger, fullness and prospective consumption ratings were measured. Participants who were more sensitive towards complex carbohydrate (maltodextrin DT) consumed significantly more maltodextrin-based milkshake in comparison with less-sensitive participants (P = 0·01) and this was independent of liking. Participants who had higher liking for glucose-based milkshake consumed significantly more glucose-based milkshake in comparison with participants with lower hedonic ratings (P = 0·049). The results provide support regarding the role of the oral system sensitivity (potentially taste) to complex carbohydrate and the prospective to overconsume complex carbohydrate-based milkshake in a single sitting.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings – regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005–2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.
Recent commercialization of auxin herbicide–based weed control systems has led to increased off-target exposure of susceptible cotton cultivars to auxin herbicides. Off-target deposition of dilute concentrations of auxin herbicides can occur on cotton at any stage of growth. Field experiments were conducted at two locations in Mississippi from 2014 to 2016 to assess the response of cotton at various growth stages after exposure to a sublethal 2,4-D concentration of 8.3 g ae ha−1. Herbicide applications occurred weekly from 0 to 14 weeks after emergence (WAE). Cotton exposure to 2,4-D at 2 to 9 WAE resulted in up to 64% visible injury, whereas 2,4-D exposure 5 to 6 WAE resulted in machine-harvested yield reductions of 18% to 21%. Cotton maturity was delayed after exposure 2 to 10 WAE, and height was increased from exposure 6 to 9 WAE due to decreased fruit set after exposure. Total hand-harvested yield was reduced from 2,4-D exposure 3, 5 to 8, and 13 WAE. Growth stage at time of exposure influenced the distribution of yield by node and position. Yield on lower and inner fruiting sites generally decreased from exposure, and yield partitioned to vegetative or aborted positions and upper fruiting sites increased. Reductions in gin turnout, micronaire, fiber length, fiber-length uniformity, and fiber elongation were observed after exposure at certain growth stages, but the overall effects on fiber properties were small. These results indicate that cotton is most sensitive to low concentrations of 2,4-D during late vegetative and squaring growth stages.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Medical procedures and patient care activities may facilitate environmental dissemination of healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus (MRSA).
Observational cohort study of MRSA-colonized patients to determine the frequency of and risk factors for environmental shedding of MRSA during procedures and care activities in carriers with positive nares and/or wound cultures. Bivariate analyses were performed to identify factors associated with environmental shedding.
A Veterans Affairs hospital.
This study included 75 patients in contact precautions for MRSA colonization or infection.
Of 75 patients in contact precautions for MRSA, 55 (73%) had MRSA in nares and/or wounds and 25 (33%) had positive skin cultures. For the 52 patients with MRSA in nares and/or wounds and at least 1 observed procedure, environmental shedding of MRSA occurred more frequently during procedures and care activities than in the absence of a procedure (59 of 138, 43% vs 8 of 83, 10%; P < .001). During procedures, increased shedding occurred ≤0.9 m versus >0.9 m from the patient (52 of 138, 38% vs 25 of 138, 18%; P = .0004). Contamination occurred frequently on surfaces touched by personnel (12 of 38, 32%) and on portable equipment used for procedures (25 of 101, 25%). By bivariate analysis, the presence of a wound with MRSA was associated with shedding (17 of 29, 59% versus 6 of 23, 26%; P = .04).
Environmental shedding of MRSA occurs frequently during medical procedures and patient care activities. There is a need for effective strategies to disinfect surfaces and equipment after procedures.
This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.
Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.
The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).
The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.
Liquid phase analysis dominates the field of blood diagnostics and requires drawing blood volumes of several ml for each test. To achieve acceptable accuracy, each single liquid blood test requires ∼7 mL per blood sample, and repeated blood tests are often needed. Frequent testing ca result in Hospital Acquired Anemia for infants, chronically ill, and critically ill patients. Blood testing methods that can be utilized with small amounts of blood are a critical need to save lives. Theranos claimed to have developed novel methods requiring only a few nL of blood. However, Theranos’ techniques led to errors that exceeded beyond the medically acceptable threshold of 10%. This work investigates solid state blood analysis using low volumes of several µL. The most common blood tests used as first line for diagnostics and monitoring patients’ status, always include blood electrolytes, iron, and in some cases, heavy metals.
The present work investigates the formation of rapidly solidified Homogeneous Thin Solid Films (HTSFs) formed from blood drops, in order to make them suitable for solid state analysis in vacuo and in air. The solidification of ∼5 micro-liter (µL)-sized blood droplets into HTSFs is studied with two goals: achieve reproducible HTSFs optimized for producing accurate analysis, and successfully measure the potential accuracy of measurements made on HTSFs for blood electrolytes Na, K, Mg, Ca, and Cl and heavy metals such as Fe.
The blood volumes selected for this work are in the µL range, one thousandth volumes drawn for current liquid phase analysis. Balanced Saline Solution (BSS) is used as an initial liquid for testing solidification uniformity and a potential calibration material. Next, canine and human blood are studied on two types of HemaDropTM coatings for solidification: super-hydrophilic and hyper-hydrophilic. HTSF formation from BSS and blood drops are compared on both coated and uncoated surfaces.
Three solid state analytical methods are investigated in parallel to probe composition at different depths and test each for reproducibility and accuracy: Ion Beam Analysis (IBA), X-ray Fluorescence (XRF), and X-ray Photoelectron Spectroscopy (XPS). The results show that using solid films of blood yields composition, which can be reproducibly measured by IBA, XPS and XRF to varying degrees. XPS’s depth of analysis, limited to ∼5 nm, probes a small fraction of the HTSF, but provides insights into the range of thickness for homogeneous compositions in HTSFs. Statistical and error analysis help establish whether measurements taken in sets of three typically used in lab fall below the medically accepted error threshold (<10%) for each technique and element detected. Measurements are repeated and taken at various locations and on different HTSFs to establish reproducibility. XRF is of particular interest, because it is fast, accurate, portable and can be conducted in air, making it ideal for areas with limited resources.
Chemical bonding in native oxides of GaAs, before and after etching, is detected by X-Ray Photoelectron Spectroscopy (XPS). It is correlated with surface energy engineering (SEE), measured via Three Liquid Contact Angle Analysis (3LCAA), and oxygen coverage, measured by High Resolution Ion Beam Analysis (HR-IBA).
Before etching, GaAs native oxides are found to be hydrophobic with an average surface energy, γT, of 33 ± 1 mJ/m2, as measured by 3LCAA. After dilute NH4OH etching, GaAs becomes highly hydrophilic and its surface energy, γT, increases by a factor 2 to a reproducible value of 66 ± 1 mJ/m2. Using HR-IBA, oxygen coverage on GaAs is found to decrease from 7.2 ± 0.5 monolayers (ML) to 3.6 ± 0.5 ML. The 1.17 ratio of Ga to As, measured by HR-IBA, remains constant after etching.
XPS is used to measure oxidation of Ga and As, as well as surface stoichiometry on two locations of several GaAs(100) wafers before and after etching. The relative proportions of Ga and As are unaffected by adventitious carbon contamination. The 1.16 Ga:As ratio, measured by XPS, matches HR-IBA analysis. The proportions of oxidized Ga and As do not change significantly after etching. However, the initial ratio of As2O5 to As2O3, within the oxidized As, significantly decreases after etching from approximately 3:1 to 3:2.
Absolute oxygen coverage, as a function of surface processing, is determined within 0.5 ML by HR-IBA. XPS offers insight into these modifications by detecting electronic states and phase composition changes of GaAs oxides. The changes in surface chemistry are correlated to changes in hydro-affinity and surface energies measured by 3LCAA.