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In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants (n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed–grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Replacement studies were conducted under greenhouse conditions to determine if available soil water influences the competitive interaction between soybean and Florida beggarweed. Stomatal conductance and leaf water potential were determined for both species under different levels of available soil water to identify possible mechanisms involved in changes in the relative competitiveness induced by the water deficits. Soybean leaf area and aboveground biomass were greater than for Florida beggarweed under optimum water, but equal to or less than Florida beggarweed with water stress. Soybean was more competitive than Florida beggarweed when there was adequate soil water but less competitive than Florida beggarweed under water stress. Stomatal conductance was higher for soybean with optimum soil water (at high leaf water potentials) but equal to Florida beggarweed as soil water became limiting (low leaf water potentials). These data indicated that water stress differentially affected soybean and Florida beggarweed.
Increasing evidence shows attachment security influences symptom expression and adaptation in people diagnosed with schizophrenia and other psychoses.
Aims
To describe the distribution of secure and insecure attachment in a cohort of individuals with first-episode psychosis, and to explore the relationship between attachment security and recovery from positive and negative symptoms in the first 12 months.
Method
The study was a prospective 12-month cohort study. The role of attachment, duration of untreated psychosis (DUP), baseline symptoms and insight in predicting and mediating recovery from symptoms was investigated using multiple regression analysis and path analysis.
Results
Of the 79 participants, 54 completed the Adult Attachment Interview (AAI): 37 (68.5%) were classified as insecure, of which 26 (48.1%) were insecure/dismissing and 11 (20.4%) insecure preoccupied. Both DUP and insight predicted recovery from positive symptoms at 12 months. Attachment security, DUP and insight predicted recovery from negative symptoms at 12 months.
Conclusions
Attachment is an important construct contributing to understanding and development of interventions promoting recovery following first-episode psychosis.
The new 1 m f/4 fast-slew Zadko Telescope was installed in June 2008 about 70 km north of Perth, Western Australia. It is the only metre-class optical facility at this southern latitude between the east coast of Australia and South Africa, and can rapidly image optical transients at a longitude not monitored by other similar facilities. We report on first imaging tests of a pilot program of minor planet searches, and Target of Opportunity observations triggered by the Swift satellite. In 12 months, 6 gamma-ray burst afterglows were detected, with estimated magnitudes; two of them, GRB 090205 (z = 4.65) and GRB 090516 (z = 4.11), are among the most distant optical transients imaged by an Australian telescope. Many asteroids were observed in a systematic 3-month search. In September 2009, an automatic telescope control system was installed, which will be used to link the facility to a global robotic telescope network; future targets will include fast optical transients triggered by high-energy satellites, radio transient detections, and LIGO gravitational wave candidate events. We also outline the importance of the facility as a potential tool for education, training, and public outreach.
This study aimed to determine whether patients with post-traumatic stress disorder (PTSD) show difficulty in recruitment of the regions of the frontal and parietal cortex implicated in top-down attentional control in the presence and absence of emotional distracters.
Method
Unmedicated individuals with PTSD (n = 14), and age-, IQ- and gender-matched individuals exposed to trauma (n = 15) and healthy controls (n = 19) were tested on the affective number Stroop task. In addition, blood oxygen level-dependent responses, as measured via functional magnetic resonance imaging, were recorded.
Results
Patients with PTSD showed disrupted recruitment of lateral regions of the superior and inferior frontal cortex as well as the parietal cortex in the presence of negative distracters. Trauma-comparison individuals showed indications of a heightened ability to recruit fronto-parietal regions implicated in top-down attentional control across distracter conditions.
Conclusions
These results are consistent with suggestions that emotional responsiveness can interfere with the recruitment of regions implicated in top-down attentional control; the heightened emotional responding of patients with PTSD may lead to the heightened interference in the recruitment of these regions.
from
Part 3
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Technology for advanced gravitational wave detectors
By
C. Zhao, University of Western Australia,
L. Ju, University of Western Australia,
S. Gras, University of Western Australia,
D. G. Blair, University of Western Australia
Edited by
D. G. Blair, University of Western Australia, Perth,E. J. Howell, University of Western Australia, Perth,L. Ju, University of Western Australia, Perth,C. Zhao, University of Western Australia, Perth
High optical power is essential for improving the sensitivity of advanced detectors. Thermal lensing, Sidles–Sigg instability and parametric instability are three dominant effects that limit the optical power required to achieve the target sensitivity. This chapter summarises these three instabilities and how they can be controlled. In particular, we emphasise parametric instability and its control.
Introduction
The first generation laser interferometer gravitational wave detectors (LIGO, Chapter 6 and Virgo, Chapter 7) have achieved their target design sensitivity, and yet this sensitivity is estimated to be only sufficient to detect large rare gravitational wave signals. To achieve detection of signals from predicted sources, a ten-fold improvement in sensitivity is required. For LIGO, this would increase the sensitive range from ~ 14 Mpc today to about ~ 200 Mpc, leading to event rates of many per year (Cutler and Thorne, 2002). To achieve this improvement the Advanced LIGO (Fritschel, 1994) and other second generation detectors require a ~ 100-fold increase in circulating laser power, in addition to improvement in the interferometer configuration, test mass thermal noise, and vibration isolation. Such high power levels create three significant challenges. The first is the control of thermal lensing in the core optics substrates and dielectric coating layers. The second is the control of parametric instabilities in the form of radiation pressure mediated opto-mechanical oscillation. The third is the control of Sidles–Sigg instabilities, which are the angular instabilities of the suspended test mass that result from radiation pressure induced optical torque.
The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)
Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using ‘preventive chemotherapy’ can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.
Wistar-Furth strain male rats and CFW strain male mice were immunized against Trichinella spiralis using an antegenic fraction derived from a cell-free homogenate of mature muscle larvae.
In rats, animlas immunized with 250 μg of antigen harboured singnificantly fewer (135000) muscle larvae 30 days after oral challenge than controls (231000). Furhter 7-day-old adult worms derived from immunized rats shed 48% fewer (P < 0·001) newborn larvae over a 24 h period in vitro than adult worms from non-immunized animals.
Mice were injected with either 10 or 100 μg of antigen. In comparison with non-immunized controls, mice immunized with 100μg of antigen harboured significantly fewer adult worms at days 7 and 9 after oral challenge infection, while female worms recovered from immune mice on days 6–10 after challenge shed fewer newborn larvae in vitro. Finally, mice immunized with 100μg of antigen harboured significantly fewer (10391) muscle larvae at 30 days after challenge than did controls (47750).
Immunization of mice with 10μ of antigen did not induce a statistically significant reduction in adult worms at either days 7 or 9 after challenge (P < 0·5). However, adult female worms from mice receiving 10μg of antigen still shed fewer larvae than did adults from control mice (P < 0·05). Mice immunized with 10μg of antigen harboured significantly fewer (13700) recoverable muscle larvae than did controls at 30 days after challenge (39000).
The recent development of low-risk imaging technologies, such as functional magnetic resonance imaging (fMRI), have had a significant impact on the investigation of psychopathologies in children and adolescents. This review considers what we can infer from fMRI work regarding the development of conduct disorder (CD) and oppositional defiant disorder (ODD). We make two central assumptions that are grounded in the empirical literature. First, the diagnoses of CD and ODD identify individuals with heterogeneous pathologies; that is, different developmental pathologies can receive a CDD or ODD diagnosis. This is indicated by the comorbidities associated with CD/ODD, some of which appear to be mutually exclusive at the biological level (e.g., posttraumatic stress disorder [PTSD] and psychopathic tendencies). Second, two populations of antisocial individuals can be identified: those that show an increased risk for only reactive aggression and those that show an increased risk for both reactive and instrumental aggression. We review the fMRI data indicating that particular comorbidities of CD/ODD (i.e., mood and anxiety conditions such as childhood bipolar disorder and PTSD) are associated with either increased responsiveness of neural regions implicated in the basic response to threat (e.g., the amygdala) or decreased responsiveness in regions of frontal cortex (e.g., ventromedial frontal cortex) that are implicated in the regulation of the basic threat response. We suggest why such pathology would increase the risk for reactive aggression and, in turn, lead to the association with a CD/ODD diagnosis. We also review the literature on psychopathic tendencies, a condition where the individual is at significantly elevated risk for both reactive and instrumental aggression. We show that in individuals with psychopathic tendencies, the functioning of the amygdala in stimulus-reinforcement learning and of the ventromedial frontal cortex in the representation of reinforcement expectancies is impaired. We suggest why such pathology would increase the risk for reactive and instrumental aggression and thus also lead to the association with a CD/ODD diagnosis.
We present results on the room temperature mechanical quality factor of single crystal calcium fluoride (CaF2) grown by the Bridgman-Stockbarger method. Resonant mode Q-factors are measured in the frequency range 20 to 76 kHz using tungsten wire loop suspensions. In spite of indications of only moderate crystal purity, we observed 6 modes with Q-factor > 107, and one with $Q = 4.5 \times10^{7}$, more than an order of magnitude higher than previously reported results.