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We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
To evaluate quality of life and patient preference for schizophrenia treatment in a community based study comparing the use of aripiprazole to the standard of care (SOC).
This open-label, 26-week, multi-centre, randomised study compared aripiprazole with SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26. The outcome research variables included the Preference of Medicine (POM) questionnaire, the Quality of Life Scale (QLS), and the EuroQoL-5D (EQ-5D). The results from these outcome research variables are the focus of this paper addressing quality of life and patient preference.
A total of 555 patients were randomised to receive aripiprazole (n = 284) or SOC (n = 271). The OC data at Week 26, reported that more respondents rated the study medication as ‘much better’ compared with their previous medication in the aripiprazole group versus SOC for patients (59% vs 35%, P < 0.001) and caregivers (58% vs 30%, P = 0.014). The improvement in QLS total score was also significantly greater in the aripiprazole group compared with SOC – mean change from baseline in QLS total score of 16.21 vs 10.01 (P < 0.001) at Week 26 (OC data set). A greater proportion of patients (93% vs 85%; P = 0.005) in the aripiprazole group had a satisfactory response on the EQ-5D Self Care Scale; all other EQ-5D scores were similar.
The study findings suggest that quality of life and patient medication preference measures were better for aripiprazole than for SOC.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Music therapy has been shown to be effective for reducing anxiety and pain in people with a serious illness. Few studies have investigated the feasibility of integrating music therapy into general inpatient care of the seriously ill, including the care of diverse, multiethnic patients. This leaves a deficit in knowledge for intervention planning. This study investigated the feasibility and effectiveness of introducing music therapy for patients on 4 inpatient units in a large urban medical center. Capacitated and incapacitated patients on palliative care, transplantation, medical intensive care, and general medicine units received a single bedside session led by a music therapist.
A mixed-methods, pre-post design was used to assess clinical indicators and the acceptability and feasibility of the intervention. Multiple regression modeling was used to evaluate the effect of music therapy on anxiety, pain, pulse, and respiratory rate. Process evaluation data and qualitative analysis of observational data recorded by the music therapists were used to assess the feasibility of providing music therapy on the units and patients’ interest, receptivity, and satisfaction.
Music therapy was delivered to 150 patients over a 6-month period. Controlling for gender, age, and session length, regression modeling showed that patients reported reduced anxiety post-session. Music therapy was found to be an accessible and adaptable intervention, with patients expressing high interest, receptivity, and satisfaction.
Significance of Results
This study found it feasible and effective to introduce bedside music therapy for seriously ill patients in a large urban medical center. Lessons learned and recommendations for future investigation are discussed.
The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.
Clusters of associated colony fragments discovered weathering out of bedding planes in the Upper Ordovician of the Cincinnati, Ohio, region provide a rare opportunity to quantify intracolony variation in ramose stenolaemate bryozoans. Sixteen colonies were reassembled as completely as possible from 198 fragments, and the following colony-level characters were measured: colony dimensions, branch link length and diameter, and branch order. Results indicate that branch link length and diameter systematically decrease as colonies grow via branch bifurcation. Branching ratio (i.e., the number of distal first-order branches divided by the number of immediately proximal second-order branches) appears to be more genetically than environmentally controlled and to be consistent among orders of stenolaemates and perhaps across the phylum. Colonies with endozones mined out by endoskeletozoans result in broken branches as opposed to pristine growing tips. This varies stratigraphically, perhaps in response to the distribution of the boring animals. The rarity of borers and the systematic proximal increase in branch diameter in these colonies suggest the zooids in the proximal portions of the colonies were alive at the time of colony death. If the time and effort can be invested in reassembling colonies, these morphometric data can then be applied to taxonomic, phylogenetic, and paleoenvironmental studies.
Most research on interventions to counter stigma and discrimination has
focused on short-term outcomes and has been conducted in high-income
To synthesise what is known globally about effective interventions to
reduce mental illness-based stigma and discrimination, in relation first
to effectiveness in the medium and long term (minimum 4 weeks), and
second to interventions in low- and middle-income countries (LMICs).
We searched six databases from 1980 to 2013 and conducted a
multi-language Google search for quantitative studies addressing the
research questions. Effect sizes were calculated from eligible studies
where possible, and narrative syntheses conducted. Subgroup analysis
compared interventions with and without social contact.
Eighty studies (n = 422 653) were included in the
review. For studies with medium or long-term follow-up (72, of which 21
had calculable effect sizes) median standardised mean differences were
0.54 for knowledge and −0.26 for stigmatising attitudes. Those containing
social contact (direct or indirect) were not more effective than those
without. The 11 LMIC studies were all from middle-income countries.
Effect sizes were rarely calculable for behavioural outcomes or in LMIC
There is modest evidence for the effectiveness of anti-stigma
interventions beyond 4 weeks follow-up in terms of increasing knowledge
and reducing stigmatising attitudes. Evidence does not support the view
that social contact is the more effective type of intervention for
improving attitudes in the medium to long term. Methodologically strong
research is needed on which to base decisions on investment in
Spatiopora Ulrich, 1882 is a trepostome bryozoan that is found encrusting living orthoconic nautiloids in the Upper Ordovician (Katian) of North America, as do several other bryozoans. These epizoozoan bryozoans are characterized by possessing thin unilaminate zoaria with rows of elongate maculae, which may be monticulate and aligned coaxially to the host growth axis. These develop a distinctive linear shape in response to growing on a conical host, rather than as a response to channelized water flow along the host. Monticules increase in size and spacing adorally until a maximum inter-macular area is reached that results in a decline in surface water flow efficiency, and a new monticular line is inserted. Orthocones normally swam forward at lower velocities that enabled lophophore eversion and feeding, which would have been impossible at the higher speeds reached when the host jetted backwards during escape. Monticules reduced drag and turbulence acting on the orthocones which allowed for more efficient venting of bryozoan macular excurrents. Characteristic elliptical monticule growth continued even after death of the motile host. A Trypanites-bryozoan-orthoconic nautiloid association shows a complex biological and taphonomic relationship between these organisms.
Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT).
This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery–Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10.
Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo).
These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.
Catecholaminergic polymorphic ventricular tachycardia is a rare life-threatening arrhythmogenic disorder. An association with paroxysmal atrial fibrillation and other atrial arrhythmias has been described, but in all published cases the initial manifestation of the disease was ventricular arrhythmia. This is the first report about a patient who presented with complex atrial tachycardia and sinus node dysfunction about 1 year before the typical ventricular arrhythmias were observed, leading to the diagnosis of catecholaminergic polymorphic ventricular tachycardia. In this girl, a mutation of the ryanodine receptor type 2 gene, which has not been described so far, was discovered.
This study is a randomized, prospective, investigation of the relationships between clinical trial design, patient expectancy and the outcome of treatment with antidepressant medication.
Adult out-patients with major depressive disorder (MDD) were randomized to either placebo-controlled (PC, 50% probability of receiving active medication) or comparator (COMP, 100% probability of receiving active medication) administration of antidepressant medication. Independent-samples t tests and analysis of covariance (ANCOVA) were used to determine whether the probability of receiving active medication influenced patient expectancy and to compare medication response in the PC v. COMP conditions. We also tested the correlations between baseline expectancy score and final improvement in depressive symptoms across study groups.
Subjects randomized to the COMP condition reported greater expectancy of improvement compared to subjects in the PC condition (t = 2.60, df = 27, p = 0.015). There were no statistically significant differences in the analyses comparing antidepressant outcomes between subjects receiving medication in the COMP condition and those receiving medication in the PC condition. Higher baseline expectancy of improvement was correlated with lower final depression severity scores (r = 0.53, p = 0.021) and greater improvement in depressive symptoms over the course of the study (r = 0.44, p = 0.058).
The methods described represent a promising way of subjecting patient expectancy to scientific study. Expectancy of improvement is affected by the probability of receiving active antidepressant medication and seems to influence antidepressant response.
Objectives: The aim of this study was to summarize and assess economic evaluations of poison centers (PCs) from the perspectives of society, the payer, and the healthcare system.
Methods: A systematic review was performed to identify complete economic evaluations regardless of the language or publication status. Two reviewers evaluated the abstracts for eligibility, extracted the data, and assessed the study quality using a standardized tool.
Results: In total, 422 non-duplicated studies were retrieved, but only nine met the eligibility criteria. Five of the eligible studies were published in the 1990s, and four were published in the 2000s. Six studies met at least seven of ten quality criteria. In all studies, the presence of PCs was compared with a scenario of their absence. Eight studies used cost–benefit analyses and one used a cost-effectiveness approach. The cost–benefit ratios ranged from 0.76 to 7.67, which indicates that each United States dollar (USD) spent on poison centers can save almost 8 USD on medical spending. A cost-effectiveness analysis showed that each successful outcome achieved by a PC avoids a minimum of 12,000 USD to 56,000 USD in other healthcare spending.
Conclusions: The data in our review show that PCs are economically viable. PCs improve the efficiency of healthcare expenditure and contribute to the sustainability of the healthcare system. An investment in PCs is a rational public health policy approach that contrasts the current trend of reducing spending on PCs.
Colony-wide feeding currents are a common feature of many bryozoan colonies. These feeding currents are centered on excurrent macular chimneys that expel previously filtered water away from the colony surface. In some bryozoans these macular chimneys consist of a branching channel network that converges at a point in the center of the chimney. The bifurcating channels of the maculae are analogous to a stream channel network in a closed basin with centripetal drainage. The classical methods of stream channel network analysis from geomorphology are here used to quantitatively analyze the number and length of macular channels in bryozoans. This approach is applied to a giant branch of the trepostome bryozoan Tabulipora from the Early Permian Kim Fjelde Formation in North Greenland. Its large size allowed 18 serial tangential peels to be made through the 8-mm-thick exozone. The peels intersected two stellate maculae as defined by contiguous exilapores. The lengths of 1460 channels radiating from the maculae were measured and their Horton-Strahler stream order and Shreve magnitude scored.
We hypothesize that if fossil bryozoan maculae function as excurrent water chimneys, then they should conform to Horton's laws of stream networks and behave like closed basins with centripetal drainage. Results indicate that the stellate maculae in this bryozoan behaved liked stream channel networks exhibiting landscape maturation and stream capture. They conformed to the Law of Stream Number. They have a Bifurcation Ratio that falls within the range of natural stream channel networks. They showed a pattern opposite that expected by the Law of Stream Lengths in response to behavior characteristic of a centripetal drainage pattern in a closed basin. Thus, the stellate maculae in this bryozoan probably functioned as excurrent water chimneys with the radiating channels serving to efficiently collect the previously filtered water, conducting it to the central chimney for expulsion away from the colony surface.
After the January 12, 2010, earthquake in Haiti, Project Medishare and the University of Miami organized, built, and staffed a 200-bed field hospital (the University of Miami Hospital in Haiti [UMHH] ) on the outskirts of Port-au-Prince. We describe the operational challenges of providing a safe environment at the UMHH. Furthermore, we compared how these issues were addressed at this ad hoc hospital with how they were addressed at the field hospital of the Israel Defense Force, a fully deployable hospital with an organization fine-tuned as a result of prior disaster situations, also in Haiti.