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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
To validate a system to detect ventilator associated events (VAEs) autonomously and in real time.
Retrospective review of ventilated patients using a secure informatics platform to identify VAEs (ie, automated surveillance) compared to surveillance by infection control (IC) staff (ie, manual surveillance), including development and validation cohorts.
The Massachusetts General Hospital, a tertiary-care academic health center, during January–March 2015 (development cohort) and January–March 2016 (validation cohort).
Ventilated patients in 4 intensive care units.
The automated process included (1) analysis of physiologic data to detect increases in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (FiO2); (2) querying the electronic health record (EHR) for leukopenia or leukocytosis and antibiotic initiation data; and (3) retrieval and interpretation of microbiology reports. The cohorts were evaluated as follows: (1) manual surveillance by IC staff with independent chart review; (2) automated surveillance detection of ventilator-associated condition (VAC), infection-related ventilator-associated complication (IVAC), and possible VAP (PVAP); (3) senior IC staff adjudicated manual surveillance–automated surveillance discordance. Outcomes included sensitivity, specificity, positive predictive value (PPV), and manual surveillance detection errors. Errors detected during the development cohort resulted in algorithm updates applied to the validation cohort.
In the development cohort, there were 1,325 admissions, 479 ventilated patients, 2,539 ventilator days, and 47 VAEs. In the validation cohort, there were 1,234 admissions, 431 ventilated patients, 2,604 ventilator days, and 56 VAEs. With manual surveillance, in the development cohort, sensitivity was 40%, specificity was 98%, and PPV was 70%. In the validation cohort, sensitivity was 71%, specificity was 98%, and PPV was 87%. With automated surveillance, in the development cohort, sensitivity was 100%, specificity was 100%, and PPV was 100%. In the validation cohort, sensitivity was 85%, specificity was 99%, and PPV was 100%. Manual surveillance detection errors included missed detections, misclassifications, and false detections.
Manual surveillance is vulnerable to human error. Automated surveillance is more accurate and more efficient for VAE surveillance.
Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.
Potassium titanyl phosphate crystals in both x-cut and z-cut were irradiated with 185 MeV Au ions. The morphology of the resulting ion tracks was investigated using small angle x-ray scattering (SAXS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). SAXS measurements indicate the presence of cylindrical ion tracks with abrupt boundaries and a density contrast of 1 ± 0.5% compared to the surrounding matrix, consistent with amorphous tracks. The track radius depends on the crystalline orientation, with 6.0 ± 0.1 nm measured for ion tracks along the x-axis and 6.3 ± 0.1 nm for those along the z-axis. TEM images in both cross-section and plan-view show amorphous ion tracks with radii comparable to those determined from SAXS analysis. The protruding hillocks covering the sample surface detected by AFM are consistent with a lower density of the amorphous material within the ion tracks compared to the surrounding matrix. Simulations using an inelastic thermal-spike model indicate that differences in the thermal conductivity along the z- and x-axis can partially explain the different track radii along these directions.
Previous studies suggest that there is a strong association between depression and cognitive decline, and that concurrent depressive symptoms in MCI patients could contribute to a difference in neurocognitive characteristics compared to MCI patients without depression. The authors tried to compare neurocognitive functions between MCI patients with and without depression by analyzing the results of neuropsychological tests.
Participants included 153 MCI patients. Based on the diagnosis of major depressive disorder, the participants were divided into two groups: depressed MCI (MCI/D+) versus non-depressed MCI (MCI/D−). The general cognitive and functional statuses of participants were evaluated. And a subset of various neuropsychological tests was presented to participants. Demographic and clinical data were analyzed using Student t-test or χ2 test.
A total of 153 participants were divided into two groups: 94 MCI/D+ patients and 59 MCI/D− patients. Age, sex, and years of education were not significantly different between the two groups. There were no significant differences in general cognitive status between MCI/D+ and MCI/D− patients, but MCI/D+ participants showed significantly reduced performance in the six subtests (Contrasting Program, Go-no-go task, Fist-edge-palm task, Constructional Praxis, Memory Recall, TMT-A) compared with MCI/D− patients.
There were significantly greater deficits in neurocognitive functions including verbal memory, executive function, attention/processing speed, and visual memory in MCI/D+ participants compared to MCI/D−. Once the biological mechanism is identified, distinct approaches in treatment or prevention will be determined.
The heterojunctions formed between solution phase grown Cu2ZnSn(SxSe1- x)4 (CZTS,Se) and a number of important buffer materials including CdS, ZnS, ZnO, and In2S3, were studied using femtosecond ultraviolet photoemission spectroscopy (fs-UPS) and photovoltage spectroscopy. With this approach we extract the magnitude and direction of the CZTS,Se band bending, locate the Fermi level within the band gaps of absorber and buffer and measure the absorber/buffer band offsets under flatband conditions. We will also discuss two-color pump/probe experiments in which the band bending in the buffer layer can be independently determined. Finally, studies of the bare CZTS,Se surface will be discussed including our observation of mid-gap Fermi level pinning and its relation to Voc limitations and bulk defects.
The 3D morphological evolution of titanium foams as they undergo a two-step fabrication process is quantitatively characterized through x-ray micro- and nano-tomography. In the first process step, a Cu–Ti–Cr–Zr prealloy is immersed in liquid Mg, where Cu is alloyed with Mg while a skeleton of crystalline Ti–Cr–Zr is created. In the second step, the Mg–Cu phase is etched in acid, leaving a Ti–Cr–Zr foam with submicron struts. 3D images of these solidified Ti–Cr–Zr/Mg–Cu composites and leached Ti–Cr–Zr foams are acquired after 5, 10, and 30 min exposure to liquid Mg. As the Mg exposure time increases, the Ti–Cr–Zr ligaments grow in size. The tortuosity loosely follows the Bruggeman relation. The interfacial surface distribution of these Ti-foams is qualitatively similar to other nano-porous metal prepared by one-step dealloying. The characteristic length of the Mg–Cu phase and pores are also reported.
Background: We performed a meta-analysis in order to determine which neuropsychological domains and tasks would be most sensitive for discriminating between patients with major depressive disorder (MDD) and healthy controls.
Methods: Relevant articles were identified through a literature search of the PubMed and Cochrane Library databases for the period between January 1997 and May 2011. A meta-analysis was conducted using the standardized means of individual cognitive tests in each domain. The heterogeneity was assessed, and subgroup analyses according to age and medication status were performed to explore the sources of heterogeneity.
Results: A total of 22 trials involving 955 MDD patients and 7,664 healthy participants were selected for our meta-analysis. MDD patients showed significantly impaired results compared with healthy participants on the Digit Span and Continuous Performance Test in the attention domain; the Trail Making Test A (TMT-A) and the Digit Symbol Test in the processing speed domain; the Stroop Test, the Wisconsin Card Sorting Test, and Verbal Fluency in the executive function domain; and immediate verbal memory in the memory domain. The Finger Tapping Task, TMT-B, delayed verbal memory, and immediate and delayed visual memory failed to separate MDD patients from healthy controls. The results of subgroup analysis showed that performance of Verbal Fluency was significantly impaired in younger depressed patients (<60 years), and immediate visual memory was significantly reduced in depressed patients using antidepressants.
Conclusions: Our findings have inevitable limitations arising from methodological issues inherent in the meta-analysis and we could not explain high heterogeneity between studies. Despite such limitations, current study has the strength of being the first meta-analysis which tried to specify cognitive function of depressed patients compared with healthy participants. And our findings may provide clinicians with further evidences that some cognitive tests in specific cognitive domains have sensitivity to discriminate MDD patients from healthy controls.
Rangea is the type genus of the Rangeomorpha, an extinct clade near the base of the evolutionary tree of large, complex organisms which prospered during the late Neoproterozoic. It represents an iconic Ediacaran taxon, but the relatively few specimens previously known significantly hindered an accurate reconstruction. Discovery of more than 100 specimens of Rangea in two gutter casts recovered from Farm Aar in southern Namibia significantly expands this data set, and the well preserved internal and external features on these specimens permit new interpretations of Rangea morphology and lifestyle. Internal structures of Rangea consist of a hexaradial axial bulb that passes into an axial stalk extending the length of the fossil. The axial bulb is typically filled with sediment, which becomes increasingly loosely packed and porous distally, with the end of the stalk typically preserved as an empty, cylindrical cone. This length of the axial structure forms the structural foundation for six vanes arranged radially around the axis, with each vane consisting of a bilaminar sheet composed of a repetitive pattern of elements exhibiting at least three orders of self-similar branching. Rangea was probably an epibenthic frond that rested upright on the sea bottom, and all known fossil specimens were transported prior to their final burial in storm deposits.
Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.
1.6 MeV He+ ions were implanted at room temperature into (0001) 4H-SiC at a dose of 1×1017 cm−2 and then annealed at 1500°C for 30 min. Small bubbles are readily observed in the as-implanted sample but also an amorphous layer. After a 1500°C annealing, recrystallization of the amorphous state occurs and large bubbles or cavities are observed. However their shape strongly depends of their location inside the buried layer. The recrystallization consists of polytypisme, 4H-SiC growth along the c-direction from the substrate, columnar 4H-SiC and epitaxial growth of 3C-SiC.