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Depression with psychotic symptoms or “psychotic depression” (PD) is a prevalent, under-diagnosed and under-treated mental disorder, which has received disproportionally little attention by clinicians, researchers and the pharmaceutical industry.
To document potential ambiguity in current treatment guidelines on PD and to determine whether such heterogeneity is reflected in the clinical practice of Danish psychiatrists.
To answer the following questions:
Is there consensus regarding first-line treatment of PD among the major treatment guidelines?
Do Danish psychiatrists treat PD in accordance with the guidelines?
Which antidepressants (AD) and antipsychotics (AP) are first-line choices among psychiatrists?
1. Review and comparison of 10 international guidelines on the treatment of PD with main focus on first-line treatment.
2. Questionnaire based survey on psychiatrists treatment of PD conducted at the annual meeting of the Danish Psychiatric Society.
Treatment guidelines had vastly different opinions on first-line treatment choice: 8/10 suggesting AD+AP combination therapy, 2/10 preferring AD monterapy and 6/10 finding ECT equally appropriate as first-line treatment. the 113 surveyed doctors reflected the same heterogeneity. the preferred first-line treatment choices where AD+AP combination therapy (41.6%), AD monotherapy (31.0%) and ECT (21.2%). the firstline choices regarding ADs and APs were TCA (51.3%) and quetiapine (62.0%) respectively.
There is clear evidence that the treatment of psychotic depression is heterogeneous, as seen in both various international guidelines and the survey of clinical practice. This is most likely due to a weak body of evidence to support clear recommendations in the guidelines.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Beliefs about the incidence of voter fraud inform how people view the trade-off between electoral integrity and voter accessibility. To better inform such beliefs about the rate of double voting, we develop and apply a method to estimate how many people voted twice in the 2012 presidential election. We estimate that about one in 4,000 voters cast two ballots, although an audit suggests that the true rate may be lower due to small errors in electronic vote records. We corroborate our estimates and extend our analysis using data from a subset of states that share social security numbers, making it easier to quantify who may have voted twice. For this subset of states, we find that one suggested strategy to reduce double voting—removing the registration with an earlier registration date when two share the same name and birthdate—could impede approximately 300 legitimate votes for each double vote prevented.
The in situ detection of organic molecules in space is key to understanding the variety and the distribution of the building blocks of life, and possibly the detection of extraterrestrial life itself. Gas chromatography mass spectrometry (GC-MS) has been the most sensitive analytical strategy for organic analyses in flight, and was used on missions from NASA's Viking, Phoenix, Curiosity missions to ESA's Rosetta space probe. While pyrolysis GC-MS revealed the first organics on Mars, this step alters or degrades certain fragile molecules that are excellent biosignatures including polypeptides, oligonucleotides and polysaccharides, rendering the intact precursors undetectable. We have identified a solution tailored to the detection of biopolymers and other biomarkers by the use of liquid-based capillary electrophoresis and electrochromatography. In this study, we show that a capillary electrochromatography approach using monolithic stationary phases with tailor-made surface chemistry can separate and identify various polycyclic aromatic hydrocarbons, nucleobases and aromatic acids that could be formed under astrophysically relevant conditions. In order to simulate flyby organic sample capture, we conducted hypervelocity impact experiments which consisted of accelerating peptide-soaked montmorillonite particles to a speed of 5.6 km s−1, and capturing them in an amorphous silica aerogel of 10 mg cm−3 bulk density. Bulk peptide extraction from aerogel followed by capillary zone electrophoresis led to the detection of only two stereoisomeric peptide peaks. The recovery rates of each step of the extraction procedure after the hypervelocity impact suggest that major peptide loss occurred during the impact. Our study provides initial exploration of feasibility of this approach for capturing intact peptides, and subsequently detecting candidate biomolecules during flight missions that would be missed by GC-MS alone. As the monolith-based electrochromatography technology could be customized to detect specific classes of compounds as well as miniaturized, these results demonstrate the potential of the instrumentation for future astrobiology-related spaceflight missions.
Although interpreters refer to the association between blackness and evil in ancient texts as essentially universal, specific reference by Christians to the counter-divine with the colour epithet ὁ μέλας is new with the Epistle of Barnabas. Black is applied as an honorific to certain Egyptian deities, but it is never used in Egyptian religion with reference to the counter-divine. Furthermore, black demons proliferate in late third- and fourth-century Egyptian monastic texts, but these witnesses postdate Barnabas. The first explicit reference to the devil as black after Barnabas is in Didymus the Blind, who interprets the reference as ‘Ethiopian’. Exploring the origin and background of this nickname for the counter-divine, this essay argues that Didymus accurately apprehends Barnabas’ intention: namely, that ‘the Black One’ does not merely reflect the universal association of blackness and evil in Roman antiquity, but, rather it reflects the appropriation of an ethnic stereotype in an apocalyptic context with distinctly anti-imperial resonances.
This study evaluated how Tactical Emergency Casualty Care (TECC) training prepared law enforcement officers (LEOs) with the tools necessary to provide immediate, on-scene medical care to successfully stabilize victims of trauma.
This was a retrospective, de-identified study using a seven-item Fairfax County (Virginia USA) TECC After-Action Questionnaire and Arlington County (Virginia USA) police reports.
Forty-six encounters were collected from 2015 through 2016. Eighty-four percent (n=39) of the encounters were from TECC After-Action Questionnaires and 15% (n=7) were from police reports. The main injuries included 13% (n=6) arterial bleeds, 46% (n=21) mild/moderate bleeds, 37% (n=17) large wounds, 20% (n=9) penetrating chest wounds, and 13% (n=6) open abdominal wounds. One-hundred percent of officers reported success in stabilizing victim injuries. Seventy-four percent of officers (n=26) did not encounter problems caring for a patient while 26% (n=9) encountered a problem. Ninety-seven percent (n=37/38) answered Yes, the training was sufficient, and three percent (n=1) indicated it was OK.
This is the most comprehensive study of TECC use among LEOs to date that supports the importance of TECC training for all LEOs in prehospital trauma care. Results of this study showed TECC training prepared LEOs with the operational tools necessary to provide immediate, on-scene medical care to successfully stabilize victims of trauma. Continuing to train increasing numbers of LEOs in TECC is key to saving the lives of victims of trauma in the future.
RothschildHR, MathiesonK.Effects of Tactical Emergency Casualty Care Training for Law Enforcement Officers. Prehosp Disaster Med.2018;33(5):495–500.
Barnabas 10 offers an allegorical discussion of kashrut. The writer addresses dietary laws in two groups of three: prohibitions against the eating of pig, vulture and eel, followed by prohibitions against eating hare, hyena and weasel. In each case, the allegorical interpretation construes diet as comportment (e.g. one should not behave like a pig, vulture etc.). Concerning the hare, readers are admonished not to emulate its corruption of children – a behaviour linked to its annual acquisition of an anus. Parallel allegorical interpretations of the Jewish food laws can be found in the Letter of Aristeas and Philo, De specialibus legibus 4 and similar quasi-scientific observations about animals occur in texts ranging from the rabbis to Physiologus. However, the rabbit poses a particular problem since no known precedent exists for either its behaviour or its physiology. The present investigation thus focuses on the rabbit, attempting to reconstruct the literary and historical background for its unusual characterisation.
Protected designation of origin dry-cured hams are obtained from heavy pigs (slaughtered at about 160 kg of live weight). A specific breeding program designed to improve meat quality for this production has included as key traits the level of intermuscular fat between the leg muscles and ham weight loss during the seasoning period together with a balance between fat and lean cuts. In this study we carried out genome-wide association studies for seven traits used in the genetic merit of Italian Duroc heavy pigs, five related to meat and carcass quality traits (visible intermuscular fat, ham weight loss at first salting, backfat thickness, ham weight and lean cuts), and two related to performance and efficiency traits (average daily gain and feed : gain ratio). A total of 573 performance-tested pigs were genotyped with the Illumina PorcineSNP60 BeadChip and genome-wide association analyses were carried out using the Bayes B approach with the 1 Mb window option of GenSel and random residuals for each of the seven traits. Detected windows were supported by independent single nucleotide polymorphism analyses with a linear mixed model (LMM) approach on the same animals for the same traits. A total of 30 windows identifying different quantitative trait loci (QTL) were detected and among those, 27 were confirmed by LMM in one of these traits. Among the confirmed windows, three QTL were reported for visible intermuscular fat, seven for ham weight loss at first salting and five and four for backfat thickness and lean cut, respectively. A total of eight QTL were detected for the other production traits. No overlapping QTL were reported except for one window on porcine chromosome 10 between lean cuts and ham weight that contained the CACNB2 gene that has been already associated with loin marbling score in other Duroc pigs. Several regions contained genes that have been already associated with production traits in other pig breeds, including Duroc lines, related to fat deposition or muscle structure. This work reports, for the first time, genome-wide association study results for several traits in Italian Duroc heavy pigs. These results will be useful to dissect the genetic basis for dry-cured ham production traits that determine the total genetic merit index of Italian Duroc pigs.
The Martian regolith is known to contain a maximum of 0.5% (w/v) perchlorate (ClO4−) that is toxic for most living organisms. With such high concentrations of perchlorates on Mars, is there any possibility of life? Here, in order to search and identify potential organisms on Earth, which could survive the perchlorate levels on Mars, we have isolated four perchlorate resistant, halophilic/halotolerant bacterial species from Big Soda Lake (BSL) in Nevada, USA. The 16S ribosomal RNA sequences revealed that these halophiles belong to the genera Bacillus, Alkalibacillus and Halomonas. Growth curves were obtained using a saline medium with different concentrations of magnesium, sodium and/or calcium perchlorate salt to simulate the Martian eutectic brine water. All four species, BSL1-4, grew in high saline media in the presence of perchlorates. This is the first growth experiment using multiple perchlorate salts. BSL3 relative to Halomonas salifodinae showed high maximum growth (Optical Density) comparing with other isolates in the presence of 1% perchlorate salts. Also, BSL1 relative to Bacillus licheniformis survived in the presence of 5% Na-perchlorate, but growth was slower in the absence of Na-perchlorate. The results revealed that these new model microbes are capable of tolerating the hypothesized hypersaline and perchlorate-rich Martian subsurface water environment. Perchlorate-resistant halophile would serve as a new model to understand the biochemistry that may occur on Mars.
Two unusual bumps occur on the internal surface of a rib of the marine reptile Prognathodon saturator from the Upper Cretaceous (Maastrichtian) of Maastricht, The Netherlands. These bumps are interpreted as stress fractures, possibly related to agonistic behaviour.
Shark bite marks on mosasaur bones abound in the fossil record. Here we review examples from Kansas (USA) and the Maastrichtian type area (SE Netherlands, NE Belgium), and discuss whether they represent scavenging and/or predation. Some bite marks are most likely the result of scavenging. On the other hand, evidence of healing and the presence of a shark tooth in an infected abscess confirm that sharks also actively hunted living mosasaurs.
Recognition of decompression syndrome-related pathology (in the form of avascular necrosis) reveals diving behaviour in mosasaurs. Macroscopic and radiologic examination was performed to identify linear bone death characteristic of avascular necrosis in vertebrae from the major North American and European collections. This survey of mosasaurs extends throughout most of their geographic and stratigraphic range and includes examples across their diversity.
Avascular necrosis was invariably present in Platecarpus coryphaeus and P. ictericus, Tylosaurus proriger, Mosasaurus lemonnieri and M. conodon, Plioplatecarpus houzeaui and Pl. primaevus, Prognathodon giganteus, Hainosaurus bernardi and an as yet unnamed Antarctic mosasaur. The frequency of occurrence in a given genus was independent of geography, present equally in European and North American and in the Niobara and Selma chalks. It was invariably absent from Clidastes propython and C. liodontus, Ectenosaurus, Halisaurus and Kolposaurus.
The bone pathology, avascular necrosis, has a characteristic distribution in seven genera and thirteen species of mosasaurs and is absent in five genera and seven species. It segregated according to diving habits, uniformly present in supposed deep divers and uniformly absent in the shallow-habitat group.
Hematite (α-Fe2O3) photoanodes are widely studied as candidates for water splitting photoelectrochemical (PEC) cells. To speed up the development of high efficiency hematite photoanodes, systematic investigations of the effect of material properties such as dopants and microstructure on PEC properties that determine the photoanode performance are crucial. Toward this end, this work presents a route for reproducible fabrication of thin film hematite photoanodes with reproducible microstructure and PEC properties. Hematite thin (50 nm) films are deposited by pulsed laser deposition from a Ti-doped (1 cation%) Fe2O3 target onto cleaned transparent conducting substrates (fluorinated tin oxide, FTO, coated glass substrates). Special attention is paid to rigorous cleaning of the substrates prior to the hematite deposition, which is found to be crucial for achieving highly reproducible results. Specimens prepared by this route display homogenous conformal coating with very little spread in PEC properties between different specimens, meeting the necessary prerequisite for systematic investigation of hematite photoanodes.
Even though technological advances could allow humans to reach Mars in the coming decades, launch costs prohibit the establishment of permanent manned outposts for which most consumables would be sent from Earth. This issue can be addressed by in situ resource utilization: producing part or all of these consumables on Mars, from local resources. Biological components are needed, among other reasons because various resources could be efficiently produced only by the use of biological systems. But most plants and microorganisms are unable to exploit Martian resources, and sending substrates from Earth to support their metabolism would strongly limit the cost-effectiveness and sustainability of their cultivation. However, resources needed to grow specific cyanobacteria are available on Mars due to their photosynthetic abilities, nitrogen-fixing activities and lithotrophic lifestyles. They could be used directly for various applications, including the production of food, fuel and oxygen, but also indirectly: products from their culture could support the growth of other organisms, opening the way to a wide range of life-support biological processes based on Martian resources. Here we give insights into how and why cyanobacteria could play a role in the development of self-sustainable manned outposts on Mars.
Knowledge about genetic diversity and population structure is useful for designing effective strategies to improve the production, management and conservation of farm animal genetic resources. Here, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture based on 244 animals sampled from 10 cattle populations in Asia and Africa and genotyped for 69 903 autosomal single-nucleotide polymorphisms (SNPs) mainly derived from the indicine breed. Principal component analysis, STRUCTURE and distance analysis from high-density SNP data clearly revealed that the largest genetic difference occurred between the two domestic lineages (taurine and indicine), whereas Ethiopian cattle populations represent a mosaic of the humped zebu and taurine. Estimation of the genetic influence of zebu and taurine revealed that Ethiopian cattle were characterized by considerable levels of introgression from South Asian zebu, whereas Bangladeshi populations shared very low taurine ancestry. The relationships among Ethiopian cattle populations reflect their history of origin and admixture rather than phenotype-based distinctions. The high within-individual genetic variability observed in Ethiopian cattle represents an untapped opportunity for adaptation to changing environments and for implementation of within-breed genetic improvement schemes. Our results provide a basis for future applications of genome-wide SNP data to exploit the unique genetic makeup of indigenous cattle breeds and to facilitate their improvement and conservation.
Feet and legs issues are some of the main causes for sow removal in the US swine industry. More timely lameness detection among breeding herd females will allow better treatment decisions and outcomes. Producers will be able to treat lame females before the problem becomes too severe and cull females while they still have salvage value. The objective of this study was to compare the predictive abilities and accuracies of weight distribution and gait measures relative to each other and to a visual lameness detection method when detecting induced lameness among multiparous sows. Developing an objective lameness diagnosis algorithm will benefit animals, producers and scientists in timely and effective identification of lame individuals as well as aid producers in their efforts to decrease herd lameness by selecting animals that are less prone to become lame. In the early stages of lameness, weight distribution and gait are impacted. Lameness was chemically induced for a short time period in 24 multiparous sows and their weight distribution and walking gait were measured in the days following lameness induction. A linear mixed model was used to determine differences between measurements collected from day to day. Using a classification tree analysis, it was determined that the mean weight being placed on each leg was the most predictive measurement when determining whether the leg was sound or lame. The classification tree’s predictive ability decreased as the number of days post-lameness induction increased. The weight distribution measurements had a greater predictive ability compared with the gait measurements. The error rates associated with the weight distribution trees were 29.2% and 31.3% at 6 days post-lameness induction for front and rear injected feet, respectively. For the gait classification trees, the error rates were 60.9% and 29.8% at 6 days post-lameness induction for front and rear injected feet, respectively. More timely lameness detection can improve sow lifetime productivity as well as animal welfare.
Unipolar psychotic depression (PD) is a highly debilitating condition, which needs intense monitoring and treatment. Among patients with recurrent PD, delusions tend to be very similar or identical over several separate episodes during the course of illness, but case reports illustrating this clinical phenomenon in detail are lacking from the literature.
Case report describing the 45-year-old Ms. J, who has experienced multiple episodes of PD. The report is based on a review of her medical file.
The delusional theme of Ms. J's initial episode of PD reappeared at several subsequent episodes. During the majority of admissions, Ms. J was treated with electroconvulsive therapy, which resulted in significant improvement in the depressive, psychotic and catatonic features.
Ms. J's case illustrates that PD can be a stable phenotype over many episodes and that it is important to recognise psychotic symptoms in order to prescribe the best possible treatment.