To save 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 saving content to .
To save content items to your Kindle, first ensure email@example.com
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
Nanocrystalline oxides are mainly responsible for Ni-base oxide dispersion strengthened (ODS) superalloys excellent thermo-mechanical properties. To establish the microstructural correlations between the metallic matrix and various oxide dispersoids, we report here the atomic-scale structure and chemistry of the complex nano-oxide dispersoids. Ultrahigh-resolution Cs-aberration-corrected scanning transmission electron microscopy (STEM) based techniques have been used to resolve nano-dispersoids in the Alloy 617 ODS. These nano-oxides, interestingly, possess a variety of high-angle annular dark-field (HAADF) contrasts, that is, bright, dark, and bi-phases. Both the light and heavy atoms have been found to be present in Y–Al–O complex-oxide nanostructures in varying quantities and forming a characteristic interface with the metallic matrix. In overcoming the limitation of conventional STEM-HAADF imaging, the integrated differential phase-contrast imaging technique was employed to investigate the oxygen atoms along with other elements in the dispersoids and its interface with the matrix. The most intriguing aspect of the study is the discovery of a few atoms thick Al2O3 interlayer (shell) around a monoclinic Y–Al–O core in the Ni-matrix. On the other hand, when the dispersoid is a hexagonal type Y–Al–O complex, the interface energy is already low, maintaining a semi-coherent interface and it was devoid of a shell.
Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
Binaural hearing is facilitated by neural interactions in the auditory pathway. Ageing results in impairment of localisation and listening in noisy situations without any significant hearing loss. The present study focused on comparing the binaural encoding of a speech stimulus at the subcortical level in middle-aged versus younger adults, based on speech-evoked auditory brainstem responses.
Thirty participants (15 young adults and 15 middle-aged adults) with normal hearing sensitivity (less than 15 dB HL) participated in the study. The speech-evoked auditory brainstem response was recorded monaurally and binaurally with a 40-ms /da/ stimulus. Fast Fourier transform analysis was utilised.
An independent sample t-test revealed a significant difference between the two groups in fundamental frequency (F0) amplitude recorded with binaural stimulation.
The present study suggested that ageing results in degradation of F0 encoding, which is essential for the perception of speech in noise.
Introduction: The Maximizing Aging Using Volunteer Engagement in the ED (MAUVE + ED) program connects specially trained volunteers with older patients whose personal and social needs are not always met within the busy ED environment. The objective of this study was to describe the development and implementation of the MAUVE + ED program and the activities performed with older patients by its volunteers. Methods: The MAUVE + ED program was implemented in the ED (annual census 65,000) of a large academic tertiary hospital in Toronto, Ontario. Volunteers were trained to identify and approach older patients and others at greater risk for adverse outcomes, including poor patient experience, in the ED and invite such patients to participate in the program. The program is available to all patients >65 years, and those with confusion, patients who were alone, those with mobility issues, and patients with increased length of stay in the ED. Volunteers documented their activities after each patient encounter using a standardized paper-based data collection form. Results: Over the program's initial 6-month period, the MAUVE + ED volunteers reported a total of 896 encounters with 718 unique patients. The median (IQR) time a MAUVE volunteer spent with a patient was 10 (5, 20) minutes, with a range of 1 to 130 minutes. The median (IQR) number of patients seen per shift was 7 (6, 9), with a range of 1 to 16 patients per shift. The most common activities the volunteer assisted with were therapeutic activities/social visits (n = 859; 95.9%), orientation activities (n = 501; 55.9%), and hydration assistance (n = 231; 25.8%). The least common were mobility assistance (n = 36; 4.0%), and vision/hearing assistance (n = 13; 1.5%). Conclusion: Preliminary data suggest the MAUVE + ED volunteers were able to enrich the experience of older adults and their families/carers in the ED.
Intellectual disability (ID) is defined as significantly subaverage intellectual functioning with deficits in adaptive behavior. For ∼40% of individuals, cause for disability remains unknown and these are categorized as idiopathic ID (IID). Various behavioral problems co-occur with ID and thus serotonergic neurotransmission, known to control emotion, mood and drive, has received immense attention. Synaptic serotonin (5-HT) level is primarily maintained by metabolizing enzyme MAOA and serotonin transporter (SLC6A4) which helps in reuptake of the neurotransmitter. Since functional genetic polymorphisms have a potency to affect activities of these proteins, in the present investigation polymorphisms in these genes (MAOA-u VNTR, rs6323, 5-HTTLPR and STIN2) have been analyzed in IID individuals associated with various behavioral problems.
Families (N=189) with IID probands were recruited following DSM-IV. After obtaining informed written consent for participation, peripheral blood was collected for isolation of genomic DNA used for PCR-based genotyping of target sites followed by family-based statistical analyses of data.
Significant association of MAOA rs6323 “T” allele with female IID (P=0.016) and a trend towards association with female IID patients exhibiting behavioral problems (P=0.046) was noticed. Non significant over transmission of the 5-HTTLPR “L” allele was also observed in female IID probands with behavioral problems (P=0.076). Synergistic epistatic interaction, with a sex-bias, was noticed between MAOA and 5-HTT (P< 0.05).
From the data obtained it could be summarized that serotonergic system may have some role in the etiology of behavioral problems of female IID individuals.
The prime focus of this work is to estimate stability and control derivatives of an airship in a completely nonlinear environment. A complete six degrees of freedom airship model has its aerodynamic model as nonlinear functions of angle of attack. Estimating the parameters of aerodynamic model in a nonlinear environment is challenging as it demands an exhaustive dataset that could cover the entire regime of operation of airship. In this work, data generation is achieved by simulating the mathematical model of airship for different trim conditions obtained from continuation analysis. The mathematical model is simulated using predicted parameter values obtained using DATCOM methodology. A modular neural network is then trained using back-propagation and Adam optimisation algorithm for each of the aerodynamic coefficients separately. The estimated nonlinear airship parameters are found to be consistent with the DATCOM parameter values which were used for open-loop simulation. This validates the proposed methodology and could be extended to estimate airship parameters from real flight data.
Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.
A cross-sectional study was conducted from 2014 to 2017 in 13 organised pig farms located in eight states of India (Northern, North-Eastern and Southern regions) to identify the risk factors, pathotype and antimicrobial resistance of Escherichia coli associated with pre- and post-weaning piglet diarrhoea. The data collected through questionnaire survey were used to identify the risk factors by univariable analysis, in which weaning status, season, altitude, ventilation in the shed, use of heater/cooler for temperature control in the sheds, feed type, water source, and use of disinfectant, were the potential risk factors. In logistic regression model, weaning and source of water were the significant risk factors. The piglet diarrhoea prevalence was almost similar across the regions. Of the 909 faecal samples collected (North – 310, North-East – 194 and South – 405) for isolation of E. coli, pathotyping and antibiotic screening, 531 E. coli were isolated in MacConkey agar added with cefotaxime, where 345 isolates were extended spectrum β-lactamase (ESBL) producers and were positive for blaCTX-M-1 (n = 147), bla TEM (n = 151), qnrA (n = 98), qnrB (n = 116), qnrS (n = 53), tetA (n = 46), tetB (n = 48) and sul1 (n = 54) genes. Multiple antibiotic resistance (MAR) index revealed that 14 (2.64%) isolates had MAR index of 1. On the virulence screening of E. coli, 174 isolates harboured alone or combination of Stx1, Stx2, eaeA, hlyA genes. The isolates from diarrhoeic and post-weaning samples harboured higher number of virulence genes than non-diarrhoeic and pre-weaning. Alleviating the risk factors might reduce the piglet diarrhoea cases. The presence of multidrug-resistant and ESBL-producing pathogenic E. coli in piglets appears a public health concern.
A cross-sectional study on six dairy farms was conducted to ascertain the occurrence of carbapenem-resistant Escherichia coli in calves. Two-hundred and seventy-nine isolates of E. coli were recovered from 90 faecal samples from apparently healthy (45) and diarrhoeal (45) calves. The isolates were screened for phenotypic susceptibility to carbapenems and production of metallo β-lactamase, as well as five carbapenemase resistance genes by PCR, and overexpression of efflux pumps. Eighty-one isolates (29.03%) were resistant to at least one of three carbapenem antibiotics [meropenem (23.30%), imipenem (2.15%) and ertapenem (1.43%)], and one isolate was positive for the blaVIM gene which was located on an Incl1 plasmid of a novel sequence type (ST 297) by multilocus sequence typing. The majority (83.95%) of isolates had an active efflux pump. Calves housed on concrete floors were approximately seven times more likely to acquire meropenem-resistant isolates than those housed on earthen floors (95% CI 1.27–41.54). In India, carbapenem drugs are not used in food animal treatment, hence carbapenem-resistant strains in calves possibly originate from the natural environment or human contact and is of public health importance. To our knowledge, this is the first report of blaVIM carbapenemases gene in calves from India.
A novel microfilarial sheath protein (MfP) of the human filarial parasite Wuchereria bancrofti and its proinflammatory activity on host macrophages were identified recently. MfP is a homolog of the nematode bestrophin-9 superfamily that acts as a ligand of macrophage Toll-like receptor 4 (TLR4) to induce inflammation through NF-κB activation. Therefore, the presence and functional implication of this novel protein in adult-stage parasites were open questions to answer. In this study, the bovine filarial parasite Setaria cervi was used to simulate adult W. bancrofti. We detected the presence of MfP in adult-stage S. cervi through clear immunological cross-reactivity and immunolocalization employing an anti-MfP antibody developed in mice. Therefore, our findings put forward S. cervi as a cost-effective source of immunodominant filarial antigen MfP to simulate its future utilization in the immunotherapeutic intervention of lymphatic filariasis.
The U.S. federal government awards a priority review voucher (“PRV”) to a pharmaceutical manufacturer after the Food and Drug Administration (“FDA”) approves a product for one of a list of voucher-eligible indications. The voucher, which can be transferred or sold, allows the company to accelerate the review timeline of another product for any indication. The PRV program was proposed in 2006 as an incentive for research and development for neglected diseases, such as dengue and leishmaniasis.
Neglected tropical diseases (“NTDs”) predominantly affect the world’s poorest populations and are associated with significant morbidity and mortality. Despite their global public health importance, neglected diseases were estimated to account for less than 1% of pharmaceutical research and development expenditures. The voucher program was intended to address this gap between investment and disease burden: “[t]he major obstacle to stimulating the R&D of new medicines for neglected diseases is lowincome nations' inability to pay for such medicines.” The voucher would provide an additional financial incentive to fund clinical development of these products without requiring additional appropriations from Congress.
This case series aimed to describe clinicoradiological, electromyographic, and etiological spectra in palatal tremor (essential=1; symptomatic=26). Patients with symptomatic palatal tremor had 2 to 10 Hz arrhythmic electromyographic bursts, a spectrum of changes in inferior olivary nucleus, with/without lesions in Guillain Mollaret triangle, and varied etiologies (genetic=9, vascular=6, trauma=3, infections=3). Exome sequencing showed variations in POLG, WDR81, NDUFS8, TENM4, and EEF2. Clinical phenotypes of patients with POLG, WDR81, and NDUFS8 variations were consistent with that described in literature. We highlight salient magnetic resonance imaging features, electrophysiological observations, and diverse etiologies in a large cohort of palatal tremor.
Chronic osteomyelitis, a bone infection caused by bacteria, requires extensive parenteral treatments. With an aim to develop bioactive glass with antibacterial properties to resist such infections, bioactive glasses with bismuth oxide as the dopant in various amounts up to 8 wt% were prepared. X-ray diffraction patterns and Fourier-transform infrared spectra of glass samples after immersion in simulated body fluid showed the presence of hydroxyapatite (HAp) and hydroxyl carbonate apatite for all samples except with the one having Bi2O3 substitution of 8 wt%. In vitro cell proliferation by MTT assay studies using a mouse fibroblast cell line (NIH3T3) have also been carried out. Primary antimicrobial activity of the glass particles was analyzed against Escherichia coli (E. coli) using broth microdilution method which exhibited bacteriostatic effects and bactericidal properties in selected samples. The combination of bioactivity, cell proliferation, and antibacterial properties of selected Bismuth-containing bioactive glasses could be exploited in treating bone-related infections.
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.