To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The Cognitive Abilities Screening Instrument (CASI) is a screening test of global cognitive function used in research and clinical settings. However, the CASI was developed using face validity and has not been investigated via empirical tests such as factor analyses. Thus, we aimed to develop and test a parsimonious conceptualization of the CASI rooted in cognitive aging literature reflective of crystallized and fluid abilities.
Secondary data analysis implementing confirmatory factor analyses where we tested the proposed two-factor solution, an alternate one-factor solution, and conducted a χ2 difference test to determine which model had a significantly better fit.
Data came from 3,491 men from the Kuakini Honolulu-Asia Aging Study.
The Cognitive Abilities Screening Instrument.
Findings demonstrated that both models fit the data; however, the two-factor model had a significantly better fit than the one-factor model. Criterion validity tests indicated that participant age was negatively associated with both factors and that education was positively associated with both factors. Further tests demonstrated that fluid abilities were significantly and negatively associated with a later-life dementia diagnosis.
We encourage investigators to use the two-factor model of the CASI as it could shed light on underlying cognitive processes, which may be more informative than using a global measure of cognition.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Background: Chest tube insertion is a time and safety critical procedure with a significant complication rate (up to 30%). Industry routinely uses Lean and ergonomic methodology to improve systems. This process improvement study used best evidence review, small group consensus, process mapping and prototyping in order to design a lean and ergonomically mindful equipment solution. Aim Statement: By simplifying and reorganising chest tube equipment, we aim to provide users with adequate equipment, reduce equipment waste, and wasted effort locating equipment. Measures & Design: The study was conducted between March 2018 and November 2018. An initial list of process steps from the best available evidence was produced. This list was then augmented by multispecialty team consensus (3 Emergency Physicians, 1 Thoracic Surgeon, 1 medical student, 2 EM nurses). Necessary equipment was identified. Next, two prototyping phases were conducted using a task trainer and a realistic interprofessional team (1 EM Physician, 1 ER Nurse, 1 Medical student) to refine the equipment list and packaging. A final equipment storage system was produced and evaluated by an interprofessional team during cadaver training using a survey and Likert scales. Evaluation/Results: There were 47 equipment items in the pre-intervention ED chest tube tray. After prototyping 21 items were removed while nine critical items were added. The nine items missing from the original design were found in four different locations in the department. Six physicians and seven RNs participated in cadaver testing and completed an evaluation survey of the new layout. Participants preferred the new storage design (Likert median 5, IQR of 1) over the current storage design (median of 1, IQR of 1). Discussion/Impact: The results suggest that the lean equipment storage is preferred by ED staff compared to the current set-up, may reduce time finding missing equipment, and will reduce waste. Future simulation work will quantitatively understand compliance with safety critical steps, user stress, wasted user time and cost.
Introduction: Chest tube insertion, a critical procedure with a published complication rate (30%), is a required competency for emergency physicians. Microskills training has been shown to identify steps that require deliberate practice. Objectives were: 1. Develop a chest tube insertion microskills checklist to facilitate IPE, 2. Compare the microskills checklist with published best available evidence, 3. Develop an educational video based on the process map, 4. Evaluate the video in an interprofessional team prior to cadaver training as a proof of concept. Methods: The study was conducted between March 2018 and November 2018. An initial list of process steps from the best available evidence was produced. This list was then augmented by multispecialty team consensus (3 Emergency Physicians, 1 Thoracic Surgeon, 1 medical student, 2 EM nurses). Two prototyping phases were conducted using a task trainer and a realistic interprofessional team (1 EM Physician, 1 ER Nurse, 1 Medical student). A final microskills list was produced and compared to the procedural steps described in consensus publications. An educational video was produced and evaluated by an interprofessional team prior to cadaver training using a survey and Likert scales as a proof of concept. Participants were 7 EM RNs and 6 ATLS trained physicians. Participants were asked to fill out a nine-question survey, using a 5-point Likert Scale (1-strongly disagree to 5 strongly agree). Results: The final process map contained 54 interdisciplinary steps, compared to ATLS that describes 14 main steps and peer reviewed articles that describe 9 main steps. The microskills checklist described, in more detail, the steps that relate to team interaction and the operational environment. Physicians rated the training video were able to apply what they learned in the video with an average of 4.67 (median of 5, mode of 5, and an IQR of 0.75). Conclusion: The development of the process maps and microkills checklists provides interprofessional teams with more information about chest tube insertion than instructions described in commonly available courses and procedural steps derived by consensus.
Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are subverted by GBM. Immunotherapies have proven incredibly successful in cancers such as melanoma, but not against GBM in part because GBM-associated MMs are not well understood. We hypothesized the content and inflammatory phenotype of MMs in GBM is variable between patients. We suspect MMs in IDH-wildtype and –mutant GBMs display divergent inflammatory phenotypes that helps explain the latter's better prognosis. Understanding GBM-associated MM heterogeneity will allow for better immunotherapy development and selection. Methods: MMs were isolated from untreated human IDH-wildtype and -mutant GBMs using flow cytometry and cultured for collection of conditioned media and analysis of secretory products. Automated segmentation with a high-content analysis system was used to quantitate MM content and inflammatory phenotype in frozen sections. New bioinformatics techniques allowed the comparison of MM profiles in publicly available single-cell RNA-sequencing databases with IDH-wildtype and -mutant GBMs. Results: Surprisingly marked variation in MM content exists between GBMs ranging from ~0-70%. A mixture of pro- and anti-inflammatory MMs are found in each GBM. Interestingly, IDH-mutant GBM-associated MMs were more activated than MMs in IDH-wildtype GBMs. Conclusions: Taken together, the highly variable MM content and phenotype of GBMs suggests the success of immunotherapies hinges on taking a precision medicine approach. MM-rich GBMs would benefit more from therapies that target them. MM activation in IDH-mutant GBMs may contribute to better patient prognoses.
Ni-based bulk metallic glasses and composites with high absolute densities exceeding 11 g/cm3 were synthesized via spark plasma sintering of Ni45Co10Ta25Nb20 powders produced from pulverized, melt-spun amorphous ribbons. Optimizing the synthesis via selection of sintering temperature, uniaxial load pressure, and powder mechanical screening yielded samples with relative densities of nearly 100% and hardness values in excess of 12.5 GPa without cracking. Mechanical testing included Weibull modulus determination for hardness and compression testing at 10-3 s-1 and 103 s-1 strain rates. The capability of using spark plasma sintering to fabricate high hardness, high density, large scale metallic glasses is demonstrated. The mechanical properties of these compacted comminuted melt-spun glass ribbons are presented.
Spintronics utilizes spin or magnetism to provide new ways to store and process information and is primarily associated with the utilization of spin polarized currents in memory and logic devices. With the end of silicon transistor technology in sight, spintronics can provide new paradigms for information processing and storage. Compared to charge based electronics, the advantages of magnetism/spin based devices are nonvolatility and ultra low power. In particular, magnetoresistive random access memories (MRAMs) are known to be “Rad Hard” [HXNV0100 64K x 16 Non-Volatile Magnetic RAM (www.honeywell.com/aerospace), S. Gerardin and A. Paccagnella, IEEE Trans. Nucl. Sci.57(6), 3016–3039 (2010), R.R. Katti, J. Lintz, L. Sundstrom, T. Marques, S. Scoppettuolo, and D. Martin, Proceedings of IEEE Radiation Effects Data Workshop, 103–105 (2009)] and are considered to be critical components for space and military systems due to their very low power consumption and nonvolatility. However, advances in the magnetic nanostructures and new materials for the scalability of MRAM and other potential applications require a re-evaluation of their radiation hardness. This review focuses mainly on recent progress in understanding the effects of irradiation on the magnetic materials and magnetic structures that are related to MRAM technology. Up to date, the most pronounced effects on the microstructures and the properties are linked to the displacement damage associated with heavy ion irradiation; however, the thermal effect is also important as it acts as an annealing process to recover the damage partially. Critical metrics for the magnetic tunnel junctions for postmortem characterizations will also be discussed. Finally, with the introduction of new perpendicular magnetic layers and the very thin MgO barrier layer in the next generation MRAM, the effects of the ionization damage shall be studied in the future.
Systematic studies on the outcome of treatment-resistant depression are
To describe the longer-term outcome and predictors of outcome in
Out of 150 patients approached, 118 participants with confirmed
treatment-resistant depression (unipolar, n= 7; bipolar,
n=27; secondary, n=14) treated in a
specialist in-patient centre were followed-up for between 8 and 84 months
The majority of participants attained full remission (60.2%), most of
whom (48.3% of total sample) showed sustained recovery (full remission
for at least 6 months). A substantial minority had persistent
subsyndromal depression (19.5%) or persistent depressive episode (20.3%).
Diagnosis of bipolar treatment-resistant depression and poorer social
support were associated with early relapse, whereas strong social
support, higher educational status and milder level of treatment
resistance measured with the Maudsley Staging Method were associated with
achieving quicker remission. Exploratory analysis of treatment found
positive associations between treatment with a monoamine oxidase
inhibitor (MAOl) in unipolar treatment-resistant depression and attaining
remission at discharge and at final follow-up, and duloxetine use
predicted attainment of remission at final follow-up.
Although many patients with treatment-resistant depression experience
persistent symptomatology even after intensive, specialist treatment,
most can achieve remission. The choice of treatment and presence of good
social support may affect remission rates, whereas those with low social
support and a bipolar diathesis should be considered at higher risk of
early relapse. We suggest that future work to improve the long-term
outcome in this disabling form of depression might focus on social
interventions to improve support, and the role of neglected
pharmacological interventions such as MAOIs.
Carers of patients with psychiatric disorders show high levels of anxiety and depression, possibly mediated through disruption of the hypothalamo–pituitary–adrenal (HPA) axis. Among carers of patients with treatment-resistant depression (TRD), we set out to determine the psychological and physiological (HPA axis) consequences of caring, and the association of these consequences with long-term outcome in patients.
Thirty-five informal carers of patients with severe TRD requiring in-patient treatment were recruited and compared with 23 controls. HPA-axis activity was assessed by measuring post-awaking salivary cortisol. The Involvement Evaluation Questionnaire (IEQ) and the General Health Questionnaire-12 (GHQ-12) were administered to measure carer burden and psychiatric caseness respectively. Independent t tests were used to compare differences between carers and controls and a linear regression model was used to determine the association of post-awakening cortisol with carer status while controlling for confounding variables. Data on long-term patient outcome (12 to 83 months), measured using the Hamilton Depression Rating Scale (HAMD), were also obtained and linear regression was used to determine the association between cortisol output in carers and remission status in patients.
Carers experienced high carer burden and high psychiatric caseness. Carers showed reduced cortisol output after awakening, calculated as the area under the curve with respect to ground (AUCg), which remained significant after controlling for potential confounders. In a linear regression model, non-remission in patients was associated with reduced cortisol output in carers.
Caring for patients with TRD is associated with adverse psychological and physiological changes suggesting hypocortisolism post-awakening. These changes are associated with poor patient outcome.
The group G streptococcus has generally not been considered a prominent pathogen. In a 1982 study of the colonization rate by β-haemoly tic streptococci in apparently healthy children, age 5–11 years, 25 of 69 isolates belonged to group G. This surprisingly high rate of group G colonization (14·3%) led to a retrospective study of school surveys in 1967 which showed that the colonization rate with this organism was 2·3% (range 1·3–3·5%). A review of bacitracin-sensitive streptococcal isolates from hospital admissions of patients with acute glomerulonephritis (AGN), rheumatic fever, and their siblings, between January 1967 and July 1980, was conducted. Of 1063 bacitracin-sensitive isolates, 63 were group G, and 52 of these were isolated from AGN patients and their siblings, i.e. 7 from skin lesions of AGN patients, 40 from the throats of siblings and only 5 from the skins of the siblings. The other 11 group G isolates were from rheumatic-fever patients and their siblings. Thus, the group G colonization rate fluctuates in the population. The isolation of only group G streptococci from skin lesions of patients with AGN suggests a possible association between group G streptococcal pyoderma and acute post-streptococcal glomerulonephritis.
People with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function.
To obtain a physiological assessment of hypothalamic–pituitary–adrenal (HPA) axis feedback status in an in-patient sample with depression and to relate this to prospectively determined severe treatment resistance.
The prednisolone suppression test was administered to 45 in-patients with depression assessed as resistant to two or more antidepressants and to 46 controls, prior to intensive multimodal in-patient treatment.
The patient group had higher cortisol levels than controls, although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ. Nonresponse to in-patient treatment was predicted by a more dysfunctional HPA axis (higher cortisol levels postprednisolone and lower percentage suppression).
In patients with severe depression, HPA axis activity is reset at a higher level, although feedback remains intact. However, prospectively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone.
Measures of episodic memory are often used to identify Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The Neuropsychological Assessment Battery (NAB) List Learning test is a promising tool for the memory assessment of older adults due to its simplicity of administration, good psychometric properties, equivalent forms, and extensive normative data. This study examined the diagnostic utility of the NAB List Learning test for differentiating cognitively healthy, MCI, and AD groups. One hundred fifty-three participants (age: range, 57–94 years; M = 74 years; SD, 8 years; sex: 61% women) were diagnosed by a multidisciplinary consensus team as cognitively normal, amnestic MCI (aMCI; single and multiple domain), or AD, independent of NAB List Learning performance. In univariate analyses, receiver operating characteristics curve analyses were conducted for four demographically-corrected NAB List Learning variables. Additionally, multivariate ordinal logistic regression and fivefold cross-validation was used to create and validate a predictive model based on demographic variables and NAB List Learning test raw scores. At optimal cutoff scores, univariate sensitivity values ranged from .58 to .92 and univariate specificity values ranged from .52 to .97. Multivariate ordinal regression produced a model that classified individuals with 80% accuracy and good predictive power. (JINS, 2009, 15, 121–129.)
A great expansion in the number of alloy compositions known to give bulk metallic glasses (BMGs) has occurred in recent years. This progress is reviewed, and factors contributing to glass-forming ability are discussed. Practical strategies for pinpointing compositions with optimum glass-forming ability are presented, with examples of their use. Consideration is also given to the wide range of possibilities for BMG-based composites.
Iron-based bulk metallic glasses (BMGs) are characterized by high fracture strengths and elastic moduli, with some exhibiting fracture strengths near 4 GPa, 2–3 times those of conventional high-strength steels. Among the Fe-based BMGs, the non-ferromagnetic ones, designated “non-ferromagnetic amorphous steel alloys” by two of the present authors [S.J. Poon et al.: Appl. Phys. Lett.83, 1131 (2003)], have glass-forming ability high enough to form single-phase glassy rods with diameters reaching 16 mm. Fe-based BMGs designed for structural applications must exhibit some plasticity under compression. However, the role of alloy composition on plastic and brittle failures in metallic glasses is largely unknown. In view of a recently observed correlation that exists between plasticity and Poisson’s ratio for BMGs, compositional effects on plasticity and elastic properties in amorphous steels were investigated. For the new amorphous steels, fracture strengths as high as 4.4 GPa and plastic strains reaching ∼0.8% were measured. Plastic failure instead of brittle failure was observed as the Poisson’s ratio approached 0.32 from below. Investigation of the relationship between the elastic moduli of the alloys and those of the alloying elements revealed that interatomic interactions in addition to the elastic moduli of the alloying elements must be considered in designing ductile Fe-based BMGs. The prospects for attaining high fracture toughness in Fe-based BMGs are discussed in this article.
The glass formability of high-manganese amorphous steel alloys reported earlier by us has been found to improve upon additions of yttrium and lanthanide elements, enabling the formation of bulk glassy samples with diameter thicknesses reaching 7 mm by casting. Based on extensive studies using different Ln additions and systematic measurements of alloy oxygen contents, the intrinsic roles of Y/Ln in attaining good glass formability in both the high-Mn alloys and previously reported high-Cr alloys are revealed. The yield strengths of the non-ferromagnetic glassy alloys obtained are estimated to be three times those of high-strength stainless steel alloys, and high elastic moduli in the range 150–200 GPa are measured. Furthermore, in the supercooled liquid regions, the glassy rods can be bent into various configurations by hand without fracturing. The observed plastic behavior together with the measured high mechanical strengths suggests that the present Fe–based bulk metallic glasses can potentially be developed as formable non-ferromagnetic amorphous steel alloys.
Report on the clinical results following bilateral globus pallidus interna deep brain stimulation in four patients (one female and three males) with severe cervical dystonia, mean age 48 years (range 37-67).
All four patients had failed extensive medical and botulinum toxin treatment. The mean duration of the disease was nine years (range 4-15 years). Patients were assessed pre and postoperatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Preoperatively, the mean TWSTRS total score was 43.2 (range 28-60.5). Posteroventral pallidal deep brain stimulators were inserted using MRI and microelectrode recording guidance. Last follow-up was 15 months for the four patients.
Mean reduction in the TWSTRS total scores at last follow- up was 73% (range 61- 85%). Improvement in pain occurred soon after deep brain stimulation surgery. Motor improvement was delayed and prolonged over several months. Frequent adjustment in the stimulation parameters was necessary in the first three months.
Bilateral pallidal stimulation is effective in management of selected cases of intractable cervical dystonia.
Fe–Cr–Mo–(Y,Ln)–C–B bulk metallic glasses (Ln are lanthanides) with maximum diameter thicknesses reaching 12 mm have been obtained by casting. The high glass formability is attained despite a low reduced glass transition temperature of 0.58. The inclusion of Y/Ln is motivated by the idea that elements with large atomic sizes can destabilize the competing crystalline phase, enabling the amorphous phase to be formed. It is found that the role of Y/Ln as a fluxing agent is relatively small in terms of glass formability enhancement. The obtained bulk metallic glasses are non-ferromagnetic and exhibit high elastic moduli of approximately 180–200 GPa and microhardness of approximately 13 GPa.
One of the major advantages of multiple-pulses Laser Thermal Annealing (LTA) with moderate energy fluence is that good dopant activation can be achieved without further increases in junction depth by successive pulses. It is demonstrated that when the laser fluence is adjusted to a value that can melt the preamorphization implantation (PAI) layer but not the underlying silicon substrate, PAI layer depths control the junction depths. Hence, it is desirable to operate LTA in this regime since this allows for a tighter process control as opposed to when the junction depth is controlled solely by the laser fluence. High Resolution Transmission Electron Microscopy (HR-TEM) micrographs show that the degree of damage repair depends on the amorphous layer thickness as well as the number of pulses. Our study allows for the evaluation of the maximum allowable PAI depth for a given number of pulses in order to fully remove the damage caused by the PAI.