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Low-intensity psychosocial interventions have been effective in targeting perinatal depression, but relevant mechanisms of change remain unknown.
To examine three theoretically informed mediators of the Thinking Healthy Programme Peer-delivered (THPP), an evidence-based psychosocial intervention for perinatal depression, on symptom severity in two parallel, randomised controlled trials in Goa, India and Rawalpindi, Pakistan.
Participants included pregnant women aged ≥18 years with moderate to severe depression, as defined by a Patient Health Questionnaire 9 (PHQ-9) score ≥10, and were randomised to either THPP or enhanced usual care. We examine whether three prespecified variables (patient activation, social support and mother–child attachment) at 3 months post-childbirth mediated the effects of THPP interventions of perinatal depressive symptom severity (PHQ-9) at the primary end-point of 6 months post-childbirth. We first examined individual mediation within each trial (n = 280 in India and n = 570 in Pakistan), followed by a pooled analysis across both trials (N = 850).
In both site-specific and pooled analyses, patient activation and support at 3 months independently mediated the intervention effects on depressive symptom severity at 6 months, accounting for 23.6 and 18.2% of the total effect of THPP, respectively. The intervention had no effect on mother–child attachment scores, thus there was no evidence that this factor mediated the intervention effect.
The effects of the psychosocial intervention on depression outcomes in mothers were mediated by the same two factors in both contexts, suggesting that such interventions seeking to alleviate perinatal depression should target both social support and patient activation levels.
We use experimental methods to investigate subsidy incidence, the transfer of subsidy payments from intended recipients to other economic agents, in privately negotiated spot markets. Our results show that market outcomes in treatments with a subsidy given to either buyers or sellers are significantly different from both a no-subsidy treatment and the competitive prediction of a 50% subsidy incidence. The disparity in incidence across treatments relative to predicted levels suggests that incidence equivalence does not hold in this market setting. Moreover, we find no statistical difference in market outcomes when benefits are framed as a “subsidy” versus a schedule shift.
A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.
To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).
After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.
This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.
As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.
Declaration of interest
I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.
Oligodeoxynucleotides (ODNs) containing cytosine-phosphate-guanosine sequence (CpG) is considered as an immune stimulator when it is fed to animals. These synthetic molecules mount different immune responses in the animals including mice, chickens, ducks, dogs and horses. CpG ODNs induce specific antigenic immunity against co-administered vaccines and are well tolerated in healthy individuals and are capable of stimulating toll-like receptors (TLRs) such as TLR-9 to activate innate immunity. The CpG ODNs can be used as an adjuvant in different vaccines synthesised specifically for poultry diseases caused by viruses and bacteria. In chickens, CpG ODNs stimulate TLRs involved in humoral immunity. CpG ODNs have been used as mucosal vaccine adjuvants against several pathogens, including avian influenza and Newcastle disease. The CpG ODNs function to protect the chickens from Newcastle disease by producing plasma dendric cells (pDCs) which ultimately produce interferons (INFs). The inoculation of CpG ODNs along with the cationic microparticles and DNA vaccine for infectious bursal disease virus result in the influx of T cells and a reduction of antigen load. When CpG ODNs are used against avian leucosis, they result in significantly higher antibody titres. In many other vaccines e.g., infectious laryngotracheitis, infectious bronchitis, herpes, viral enteritis, Marek's disease virus, E. coli and Salmonella spp. including CpG ODNs exhibit immunostimulatory effects. In conclusion, CpG ODNs may be used as effective adjuvants in viral, bacterial and parasitic vaccines in poultry.
Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C. difficile antigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenic C. difficile colonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22 C. difficile strains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis, C. difficile colonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (both P < 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey. C. difficile colonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.
The aim of this feasibility trial was to evaluate the feasibility and acceptability of the locally adapted Group Problem Management Plus (PM+) intervention for women in the conflict affected settings in Swat, Pakistan.
This mixed-methods study incorporated a quantitative component consisting of a two arm cluster randomised controlled feasibility trial, and qualitative evaluation of the acceptability of the Group PM+ to a range of stakeholder groups. For the quantitative component, on average from each of the 20 Lady Health Workers (LHWs) catchment area (20 clusters), six women were screened and recruited for the trial with score of >2 on the General Health Questionnaire and score of >16 on the WHO Disability Assessment Schedule. These LHW clusters were randomised on a 1 : 1 allocation ratio using a computer-based software through a simple randomisation method to the Group PM+ intervention or Enhanced Usual Care. The Group PM+ intervention consisted of five weekly sessions of 2 h duration delivered by local non-specialist females under supervision. The primary outcome was individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 7th week after baseline. Secondary outcomes include symptoms of depression, post-traumatic stress disorder (PTSD), general psychological profile, levels of functioning and generalised psychological distress. Intervention acceptability was explored through in-depth interviews.
The results show that lay-helpers with no prior mental health experience can be trained to achieve the desired competency to successfully deliver the intervention in community settings under supervision. There was a good intervention uptake, with Group PM+ considered useful by participants, their families and lay-helpers. The outcome evaluation, which was not based on a large enough study to identify statistically significant results, indicated statistically significant improvements in depression, anxiety, general psychological profile and functioning. The PTSD symptoms and depressive disorder scores showed a trend in favour of the intervention.
This trial showed robust acceptance in the local settings with delivery by non-specialists under supervision by local trained females. The trial paves the way for further adaptation and exploration of the outcomes through larger-scale implementation and definitive randomised controlled trials in the local settings.
The Permian is regarded as one of the most crucial intervals during echinoid evolution because crown group echinoids are first widely known from the Permian. New faunas provide important information regarding the diversity of echinoids during this significant interval as well as the morphological characterization of the earliest crown group and latest stem group echinoids. A new fauna from the Capitanian Lamar Member of the Bell Canyon Formation in the Guadalupe Mountains of West Texas comprises at least three new taxa, including Eotiaris guadalupensis Thompson n. sp. an indeterminate archaeocidarid, and Pronechinus? sp. All specimens represented are silicified and known from disarticulated or semiarticulated interambulacral and ambulacral plates and spines. This assemblage is one of the most diverse echinoid assemblages known from the Permian and, as such, informs the paleoecological setting in which the earliest crown group echinoids lived. This new fauna indicates that crown group echinoids occupied the same environments as stem group echinoids of the Archaeocidaridae and Proterocidaridae. Furthermore, the echinoids described herein begin to elucidate the order of character transitions that likely took place between stem group and crown group echinoids. At least one of the morphological innovations once thought to be characteristic of early crown group echinoids, crenulate tubercles, was in fact widespread in a number of stem group taxa from the Permian as well. Crenulate tubercles are reported from two taxa, and putative cidaroid style U-shaped teeth are present in the fauna. The presence of crenulate tubercles in the archaeocidarid indicates that crenulate tubercles were present in stem group echinoids, and thus the evolution of this character likely preceded the evolution of many of the synapomorphies that define the echinoid crown group.
The loss of information resulting from taphonomic degradation could represent a significant bias in the study of morphological diversity. This potential bias is even more concerning given the uneven effect of taphonomy across taxonomic groups, depositional facies, and stratigraphic successions and in response to secular changes through the Phanerozoic. The effect of taphonomic degradation is examined using character-based morphological data sets describing disparity in Paleozoic crinoids and blastozoans. Characters were sequentially excluded from the analyses following progressive taphonomic loss to determine how morphologic metrics, such as the relative distribution of taxa in morphospace and partial disparity, changed with increasing taphonomic alteration. Blastozoans showed very little change in these metrics with decreasing preservational quality, which is a result of characters that create distance in morphospace being recognizable in isolated plates. The opposite result is present in crinoids as the characters that are important in structuring the morphospace require intact modules (i.e., the calyx) to accurately assess. Temporal and stratigraphic trends produced encouraging results in that patterns could be largely recovered even with exaggerated taphonomic biases. However, certain parts of a stratigraphic sequence should be avoided and morphological outliers could potentially play a larger role through time, though both of these biases can be easily identified and avoided. The methods presented in this study provide a way to assess potential taphonomic biases in character-based studies of morphological diversity.
A major goal of biological classification is to provide a system that conveys phylogenetic relationships while facilitating lucid communication among researchers. Phylogenetic taxonomy is a useful framework for defining clades and delineating their taxonomic content according to well-supported phylogenetic hypotheses. The Crinoidea (Echinodermata) is one of the five major clades of living echinoderms and has a rich fossil record spanning nearly a half billion years. Using principles of phylogenetic taxonomy and recent phylogenetic analyses, we provide the first phylogeny-based definition for the Clade Crinoidea and its constituent subclades. A series of stem- and node-based definitions are provided for all major taxa traditionally recognized within the Crinoidea, including the Camerata, Disparida, Hybocrinida, Cladida, Flexibilia, and Articulata. Following recommendations proposed in recent revisions, we recognize several new clades, including the Eucamerata Cole 2017, Porocrinoidea Wright 2017, and Eucladida Wright 2017. In addition, recent phylogenetic analyses support the resurrection of two names previously abandoned in the crinoid taxonomic literature: the Pentacrinoidea Jaekel, 1918 and Inadunata Wachsmuth and Springer, 1885. Last, a phylogenetic perspective is used to inform a comprehensive revision of the traditional rank-based classification. Although an attempt was made to minimize changes to the rank-based system, numerous changes were necessary in some cases to achieve monophyly. These phylogeny-based classifications provide a useful template for paleontologists, biologists, and non-experts alike to better explore evolutionary patterns and processes with fossil and living crinoids.
The extraxial axial theory is used to investigate homology of ambulacral and oral plating because it predicts terminal branching and terminal addition of plates in the axial skeleton, although exceptions to the former may occur in some Paleozoic echinoderms. The variety of morphological designs and anomalous individuals also provide tests of plate homology. Homology of ambulacra is generally accepted, with the hydropore and/or single gonopore in Carpenter’s CD interray. In the 2-1-2 ambulacral pattern the unbranched ambulacrum is always in Carpenter’s A ray. All ambulacral morphology requires just three instructions: ‘grow,’ ‘branch,’ and ‘stop.’ The range of variation in echinoderms with fewer than five ambulacra implies that both the ‘branch’ and ‘stop’ instructions acted independently in all five rays. Numbers of ambulacra may or may not correlate with numbers of orals. Two basic patterns of ‘cystoid’ oral plating occur; with a single radial (circum-oral, CO) plate from each ambulacrum plus a sixth in the CD interray, and with all six interradial peri-oral (PO) plates, with two in the CD interambulacrum. Five ‘orals’ may involve loss of PO3 or PO6. Erect ambulacral structures are lost first in taphonomy and so poorly known. All ambulacral skeletal elements bear the same topological relationship to ambulacral soft tissues. Where branched ambulacra occur, the trunk or flooring plates are often modified first brachiolars or pinnulars. Both brachioles and pinnules may arise from facets developed on one or two flooring plates. Terminal addition of plates, spacing of brachioles/pinnules, and lack of musculature to open cover plates all suggest that ‘cystoids’ had extensions of the water vascular system in their ambulacra.
The subclass Camerata (Crinoidea, Echinodermata) is a major group of Paleozoic crinoids that represents an early divergence in the evolutionary history and morphologic diversification of class Crinoidea, yet phylogenetic relationships among early camerates remain unresolved. This study conducted a series of quantitative phylogenetic analyses using parsimony methods to infer relationships of all well-preserved Ordovician camerate genera (52 taxa), establish the branching sequence of early camerates, and test the monophyly of traditionally recognized higher taxa, including orders Monobathrida and Diplobathrida. The first phylogenetic analysis identified a suitable outroup for rooting the Ordovician camerate tree and assessed affinities of the atypical dicyclic family Reteocrinidae. The second analysis inferred the phylogeny of all well-preserved Ordovician camerate genera. Inferred phylogenies confirm: (1) the Tremadocian genera Cnemecrinus and Eknomocrinus are sister to the Camerata; (2) as historically defined, orders Monobathrida and Diplobathrida do not represent monophyletic groups; (3) with minimal revision, Monobathrida and Diplobathrida can be re-diagnosed to represent monophyletic clades; (4) family Reteocrinidae is more closely related to camerates than to other crinoid groups currently recognized at the subclass level; and (5) several genera in subclass Camerata represent stem taxa that cannot be classified as either true monobathrids or true diplobathrids. The clade containing Monobathrida and Diplobathrida, as recognized herein, is termed Eucamerata to distinguish its constituent taxa from more basally positioned taxa, termed stem eucamerates. The results of this study provide a phylogenetic framework for revising camerate classification, elucidating patterns of morphologic evolution, and informing outgroup selection for future phylogenetic analyses of post-Ordovician camerates.
A diverse crinoid fauna is described from the Upper Ordovician (Katian) Fombuena Formation from the eastern Iberian Chains of Spain. New crinoids include the diplobathrid camerates Fombuenacrinus nodulus n. gen. n. sp., Goyacrinus gutierrezi n. gen. n. sp., Dalicrinus hammanni n. gen. n. sp., and Ambonacrinus decorus n. gen. n. sp.; the monobathrid camerate Eopatelliocrinus hispaniensis n. sp.; and the cladid Picassocrinus villasi n. gen. n. sp. A new occurrence of Heviacrinus melendezi Gil Cid, Domínguez Alonso, and Silván Pobes, 1996 is also documented from the Castillejo Formation (Darriwilian, Middle Ordovician) from the eastern Iberian Chains of Spain. The Fombuena Formation comprises a Gondwanan crinoid assemblage from a high paleolatitude and has the highest crinoid diversity of any currently known Katian Gondwanan fauna. This assemblage is compared to other Katian age faunas around the globe, and its paleobiogeographic implications are discussed.
Conservation agriculture (CA) is inadequately developed for rice-based cropping systems widely practiced in Bangladesh. The current drawback is the implementation of CA for all crops including rice (Oryza sativa L., ecotype ‘transplanted aman’ [T. aman]) to increase rice–wheat (Triticum aestivum L.) rotation productivity. It is important to identify the best combination of tillage types and cropping systems to achieve a high yield of component crops and improve soil health. Three tillage practices, assigned to main experimental plots [namely, zero tillage (ZT), conventional tillage using a rotary tiller (CT) and deep tillage using a chisel plough (DT)] and three different cropping systems, assigned to sub-plots [namely, WFT: wheat–fallow–T. aman, WMT: wheat–mungbean (Vigna radiata L. Wilczek)–T. aman and WDT: wheat–dhaincha (Sesbania rostrata)–T. aman], were tested. After 4 years, ZT under WDT and WMT significantly increased soil organic matter (SOM) at 0–150 mm depth, and these replicates also held the highest levels of total organic carbon. Soil organic carbon (C) increased at a rate of 1.17 and 1.14 t/ha/y in ZT under WDT and WMT, respectively, while CT and DT under WFT were almost unchanged. After 4 years, SOM build-up by the three-crop system (WDT and WMT) under ZT helped conserve soil moisture and improve other soil properties, such as reduction in soil strength and bulk density and increase plant available water content, thus maintaining an optimum soil water infiltration rate. Zero tillage under WMT and WDT showed significant improvements in root mass density of rice and wheat at increased soil depth. The WDT and WMT plots under DT consistently gave the highest yield followed by WDT and WMT under CT, in contrast with ZT under WMT or WDT, which showed the highest improvement in crop yields over the years. In summary, minimum soil disturbance together with incorporation of a legume/green manure crop into the rice–wheat system as well as the retention of their residues increased soil C status, improved soil properties and maximized grain yields.
The role of ferroelectric LiNbO3 (LNB) in altering the frequency dependence of the capacitance of CaCu3Ti4O12 (CCTO) thin films has been investigated. A cost effective spin coating deposition process was used to integrate the oxide heterostructures onto silicon substrates. This study showed that the frequency stability of the CCTO/LNB structure was much improved when the crystallization conditions and physical dimension of each layer were optimized. To integrate this structure with current silicon technology, heterostructures of CCTO and LNB thin films were fabricated on HF terminated Si using chemical solution deposition. It was found that the order of deposition of the two layers was important for the structural quality of the heterostructures with the CCTO layer followed by the LNB layer being the preferred structure. In addition to improvement of the capacitance variation with frequency, the heterostructures also provide a path to tuning the frequency of operation.
A systematic x-ray diffraction (XRD) study was performed on room-temperature Xe-irradiated and postirradiation annealed CeO2. Large scale XRD did not show any additional irradiation-induced phases upon irradiation. Depth profiling the CeO2 (111) diffraction peak over the 150 nm deep Xe-irradiated layer (400 keV, 1 × 1020 Xe/m2) by grazing incidence XRD indicated a lattice expansion at the irradiated layer. Postirradiation annealing (1 h at 1000 °C) in an oxygen-containing environment removed the observed XRD features. Electron energy loss spectroscopy (EELS) was performed for cross-sectional samples before and after postirradiation annealing. EELS showed that the Ce charge state changed from +4 to +3 at the CeO2 surface indicating the presence of O vacancies in both as-irradiated and annealed samples. EELS also indicated that the amount of O vacancies was reduced at the irradiated region by annealing. The experimental results are discussed based on electronic properties of CeO2, annihilation of oxygen vacancies, and evolution of irradiation damage.
There is limited information on percent expenditure of household income due to childhood diarrhoea especially in rural Bangladesh. A total of 4205 children aged <5 years with acute diarrhoea were studied. Percent expenditure was calculated as total expenditure for the diarrhoeal episode divided by monthly family income, multiplied by 100. Overall median percent expenditure was 3·04 (range 0·01–94·35). For Vibrio cholerae it was 6·42 (range 0·52–82·85), for enterotoxigenic Escherichia coli 3·10 (range 0·22–91·87), for Shigella 3·17 (range 0·06–77·80), and for rotavirus 3·08 (range 0·06–48·00). In a multinomial logistic regression model, for the upper tertile of percent expenditure, significant higher odds were found for male sex, travelling a longer distance to reach hospital (⩾median of 4 miles), seeking care elsewhere before attending hospital, vomiting, higher frequency of purging (⩾10 times/day), some or severe dehydration and stunting. V. cholerae was the highest and rotavirus was the least responsible pathogen for percent expenditure of household income due to childhood diarrhoea.
Soil contaminated with helminth eggs and protozoan cysts is a potential source of infection and poses a threat to the public, especially to young children frequenting playgrounds. The present study determines the levels of infection of helminth eggs in soil samples from urban and suburban playgrounds in five states in Peninsular Malaysia and identifies one source of contamination via faecal screening from stray animals. Three hundred soil samples from 60 playgrounds in five states in Peninsular Malaysia were screened using the centrifugal flotation technique to identify and determine egg/cyst counts per gram (EPG) for each parasite. All playgrounds, especially those in Penang, were found to be contaminated with eggs from four nematode genera, with Toxocara eggs (95.7%) the highest, followed by Ascaris (93.3%), Ancylostoma (88.3%) and Trichuris (77.0%). In addition, faeces from animal shelters were found to contain both helminth eggs and protozoan cysts, with overall infection rates being 54% and 57% for feline and canine samples, respectively. The most frequently occurring parasite in feline samples was Toxocara cati (37%; EPG, 42.47 ± 156.08), while in dog faeces it was Ancylostoma sp. (54%; EPG, 197.16 ± 383.28). Infection levels also tended to be influenced by season, type of park/playground and the texture of soil/faeces. The occurrence of Toxocara, Ancylostoma and Trichuris eggs in soil samples highlights the risk of transmission to the human population, especially children, while the presence of Ascaris eggs suggests a human source of contamination and raises the issue of hygiene standards and public health risks at sites under investigation.