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Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Angiostrongylus cantonensis is a pathogenic nematode and the cause of neuroangiostrongyliasis, an eosinophilic meningitis more commonly known as rat lungworm disease. Transmission is thought to be primarily due to ingestion of infective third stage larvae (L3) in gastropods, on produce, or in contaminated water. The gold standard to determine the effects of physical and chemical treatments on the infectivity of A. cantonensis L3 larvae is to infect rodents with treated L3 larvae and monitor for infection, but animal studies are laborious and expensive and also raise ethical concerns. This study demonstrates propidium iodide (PI) to be a reliable marker of parasite death and loss of infective potential without adversely affecting the development and future reproduction of live A. cantonensis larvae. PI staining allows evaluation of the efficacy of test substances in vitro, an improvement upon the use of lack of motility as an indicator of death. Some potential applications of this assay include determining the effectiveness of various anthelmintics, vegetable washes, electromagnetic radiation and other treatments intended to kill larvae in the prevention and treatment of neuroangiostrongyliasis.
The archaeological site of Saruq al-Hadid, Dubai, United Arab Emirates, presents a long sequence of persistent temporary human occupation on the northern edge of the Rub’ al-Khali desert. The site is located in active dune fields, and evidence for human activity is stratified within a deep sequence of natural dune deposits that reflect complex taphonomic processes of deposition, erosion and reworking. This study presents the results of a program of radiocarbon (14C) and thermoluminescence dating on deposits from Saruq al-Hadid, allied with studies of material remains, which are amalgamated with the results of earlier absolute dating studies provide a robust chronology for the use of the site from the Bronze Age to the Islamic period. The results of the dating program allow the various expressions of human activity at the site—ranging from subsistence activities such as hunting and herding, to multi-community ritual activities and large scale metallurgical extraction—to be better situated chronologically, and thus in relation to current debates regarding the development of late prehistoric and early historic societies in southeastern Arabia.
The increased use of insecticide seed treatments in rice has raised many questions about the potential benefits of these products. In 2014 and 2015, a field experiment was conducted near Stuttgart and Lonoke, AR, to evaluate whether an insecticide seed treatment could possibly lessen injury from acetolactate synthase (ALS)–inhibiting herbicides in imidazolinone-resistant (IR) rice. Two IR cultivars were tested (a hybrid, ‘CLXL745’, and an inbred, ‘CL152’), with and without an insecticide seed treatment (thiamethoxam). Four different herbicide combinations were evaluated: a nontreated control, two applications of bispyribac-sodium (hereafter bispyribac), two applications of imazethapyr, and two applications of imazethapyr plus bispyribac. The first herbicide application was to two- to three-leaf rice, and the second immediately prior to flooding (one- to two-tiller). At both 2 and 4 wk after final treatment (WAFT), the sequential applications of imazethapyr or bispyribac plus imazethapyr were more injurious to CLXL745 than CL152. This increased injury led to decreased groundcover 3 WAFT. Rice treated with thiamethoxam was less injured than nontreated rice and had improved groundcover and greater canopy heights. Even with up to 32% injury, the rice plants recovered by the end of the growing season, and yields within a cultivar were similar with and without a thiamethoxam seed treatment across all herbicide treatments. Based on these results, thiamethoxam can partially protect rice from injury caused by ALS-inhibiting herbicides as well as increase groundcover and canopy height; that is, the injury to rice never negatively affected yield.
The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.
We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.
The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.
The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.
Spray drying is shown to be an effective and rapid method for preparing samples for quantitative analysis by x-ray powder diffraction. Previously intractable problems like the simultaneous analysis of multiple phases in orientation prone systems can be carried out. Using this method, and a computer controlled diffractometer, five and six phase analyses of Devonian shales can be accomplished in approximately forty minutes. A rapid and convenient method for using the absorption diffraction technique for x-ray quantitative analysis is described.
The spray drying of powders is a method of forming spherical or torroidal shaped agglomerates. A relatively simple method is given for preparing spray dried samples of the quantities used in x-ray diffraction analysis. This technique is shown to minimize preferred orientation effects on diffraction intensities from materials of widely differing symmetry and crystallite habit.
The recent discovery of ferroelectric behavior in doped hafnia-based dielectrics, attributed to a non-centrosymmetric orthorhombic phase, has potential for use in attractive applications such as negative differential capacitance field-effect-transistors (NCFET) and ferroelectric random access memory devices (FeRAM). Alloying with similar oxides like ZrO2, doping with specific elements such as Si, novel processing methods, encapsulation and annealing schemes are also some of the techniques that are being explored to target structural modifications and stabilization of the non-centrosymmetric phase. In this study, we utilized synchrotron-based x-ray diffraction in the grazing incidence in plane geometry (GIIXRD) to determine the crystalline phases in hafnia-zirconia (HZO) compositional alloys deposited by atomic layer deposition (ALD). Here we compare and contrast the structural phases and ferroelectric properties of mechanically confined HZO films in metal-insulator-metal (MIM) and metal-insulator-semiconductor (MIS) structures. Both MIM and MIS structures reveals a host of reflections due to non-monoclinic phases in the d-spacing region between 1.75Å to 4Å. The non-monoclinic phases are believed to consist of tetragonal and orthorhombic phases. Compared to the MIS structures a suppression of the monoclinic phase in MIM structures with 50% zirconia or less was observed. The correlation of the electrical properties with the structural analysis obtained by GIIXRD highlights the importance of understanding the effects of the underlying substrate (metal vs. Si) for different target applications.
Can the structure of genetic and environmental influences on normative personality traits (NPTs), abnormal personality traits (APTs), and DSM-IV criteria for personality disorders (PD) fit a high or low congruence model positing, respectively, close or more limited etiologic continuity?
Exploratory factor analysis was applied to transformed correlation matrices from Cholesky twin decompositions obtained in OpenMx. In 2801 adult twins from the Norwegian Institute of Public Health Twin Panel, NPTs and APTs were assessed by self-report using the Big Five Inventory (BFI) and PID-5-Norwegian Brief Form (PID-5-NBF), respectively. PDs were assessed at interview using the Structured Interview for DSM-IV Personality (SIDP-IV).
The best model yielded three genetic and three unique environmental factors. Genetic factors were dominated, respectively, by (i) high loadings on nearly all PDs and NPT/APT neuroticism and compulsivity, (ii) negative loadings on NPT agreeableness/conscientiousness and positive loadings on APT/PD measures of antisocial traits, and (iii) negative loadings on NPT extraversion and histrionic PD, and positive loadings on APT detachment and schizoid/avoidant PD. Unique environmental factors were dominated, by (i) high loadings on all PDs, (ii) high loadings on all APT dimensions and NPT neuroticism, and (iii) negative loadings on NPT extraversion and positive loadings on NPT detachment/avoidant PD.
Two genetic and one environmental common factor were consistent with a high congruence model while one genetic and two environmental factors were more supportive of a low congruence model. The relationship between genetic and environmental influences on personality assessed by NPTs, APTs, and PDs is complex and does not fit easily into a low or high congruence model.
Lumateperone is a first-in-class agent in development for schizophrenia that acts synergistically through serotonergic, dopaminergic and glutamatergic systems. Lumateperone is a potent 5-HT2A antagonist, a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonist and post-synaptic antagonist activity at D2, a glutamate GluN2B receptor phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway and an inhibitor of serotonin reuptake.
Lumateperone was evaluated in 3 controlled clinical trials to evaluate efficacy in patients with acute schizophrenia. The primary endpoint was change from baseline on the PANSS total score compared to placebo. In Study ‘005, 335 patients were randomized to receive ITI-007 60mg or 120mg , risperidone 4mg (active control) or placebo QAM for 4weeks. In Study ‘301, 450 patients were randomized to receive ITI-007 60mg or 40mg , or placebo QAM for 4weeks. In Study ‘302, 696 patients were randomized to receive ITI-007 60mg or 20mg , risperidone 4mg (active control) or placebo QAM for 6weeks. Also, an open-label safety switching study was conducted in which 302 patients with stable schizophrenia were switched from standard-of-care (SOC) antipsychotics and treated for 6weeks with lumateperone QPM and then switched back to SOC.
In Studies ‘005 and ‘301, lumateperone (60mg ITI-007) met the primary endpoint with statistically significant superior efficacy over placebo at Day 28. In Study ‘302, neither dose of lumateperone separated from placebo on the primary endpoint; a high placebo response was observed in this study. Across all 3 efficacy trials, lumateperone improved symptoms of schizophrenia with the same trajectory and same magnitude of improvement from baseline to endpoint on the PANSS total score.
Lumateperone was well-tolerated with a favorable safety profile in all studies. In the two studies with risperidone included as an active control, lumateperone was statistically significantly better than risperidone on key safety and tolerability measures. In the open-label safety switching study statistically significant improvements from SOC were observed in body weight, cardiometabolic and endocrine parameters worsened again when switched back to SOC medication. In this study, symptoms of schizophrenia generally remained stable or improved. Greater improvements were observed in subgroups of patients with elevated symptomatology (comorbid symptoms of depression and those with prominent negative symptoms).
Lumateperone represents a novel approach to the treatment of schizophrenia with a favorable safety profile in clinical trials. The lack of cardiometabolic and motor safety issues presents a safety profile differentiated from standard-of-care antipsychotic therapy.
Funding Acknowledgements: Intra-Cellular Therapies, Inc.
Varroa destructor mites (Acari: Varroidae) are harmful ectoparasites of Apis mellifera honey bees. Female foundresses of wax-capped pupal host cells and their daughters feed on host fluids from open wounds on the host's integument. Details of V. destructor mite nutrition are forthcoming, and little is known about the potential physical effects on hosts from mite feeding. Chemical analysis of waste excretions can infer details of animals’ nutrition. Here, chemical analysis by high-performance liquid chromatography/mass spectrometry (HPLC-MS/MS) of mite excretions showed that the purine content of V. destructor waste consists of guanine with traces of hypoxanthine. Traces of uric acid and caffeine were also detected. Concentrations of guanine attenuated over time and excretions collected from senescing mites did not contain detectable guanine. Non-reproducing individual female mites maintained in vitro, housed in gelatin capsules and provided a honey bee pupa, deposited an average of nearly 18 excretions daily, mostly on the host's integument rather than on the capsule wall. The weight and volume of excretions suggest mites can consume nearly a microlitre of host fluids each day. Compounded over 10 days, this together with open wounds, could lead to substantial water loss and stress to developing pupae.
Normative and pathological personality traits have rarely been integrated into a joint large-scale structural analysis with psychiatric disorders, although a recent study suggested they entail a common individual differences continuum.
We explored the joint factor structure of 11 psychiatric disorders, five personality-disorder trait domains (DSM-5 Section III), and five normative personality trait domains (the ‘Big Five’) in a population-based sample of 2796 Norwegian twins, aged 19‒46.
Three factors could be interpreted: (i) a general risk factor for all psychopathology, (ii) a risk factor specific to internalizing disorders and traits, and (iii) a risk factor specific to externalizing disorders and traits. Heritability estimates for the three risk factor scores were 48% (95% CI 41‒54%), 35% (CI 28‒42%), and 37% (CI 31‒44%), respectively. All 11 disorders had uniform loadings on the general factor (congruence coefficient of 0.991 with uniformity). Ignoring sign and excluding the openness trait, this uniformity of factor loadings held for all the personality trait domains and all disorders (congruence 0.983).
Based on our findings, future research should investigate joint etiologic and transdiagnostic models for normative and pathological personality and other psychopathology.
In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors.
In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models.
A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002).
In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.
Each year there are multiple reports of drift occurrences, and the majority of drift complaints in rice are from imazethapyr or glyphosate. In 2014 and 2015, multiple field experiments were conducted near Stuttgart, AR, and near Lonoke, AR, to evaluate whether insecticide seed treatments would reduce injury from glyphosate or imazethapyr drift or decrease the recovery time following exposure to a low rate of these herbicides. Study I was referred to as the “seed treatment study,” and Study II was the “drift timing study.” In the seed treatment study the conventional rice cultivar ‘Roy J’ was planted, and herbicide treatments included imazethapyr at 10.5 g ai ha–1, glyphosate at 126 g ae ha–1, or no herbicide. Each plot had either a seed treatment of thiamethoxam, clothianidin, chlorantraniliprole, or no insecticide seed treatment. The herbicides were applied at the two- to three-leaf growth stage. Crop injury was assessed 1, 3, and 5 wk after application. Averaged over site-years, thiamethoxam-treated rice had less injury than rice with no insecticide seed treatment at each rating, along with an increased yield. Clothianidin-treated rice had an increased yield over no insecticide seed treatment, but the reduction in injury for both herbicides was less pronounced than in the thiamethoxam-treated plots. Overall, chlorantraniliprole was generally the least effective of the three insecticides in reducing injury from either herbicide and in protecting rice yield potential. A second experiment conducted at Stuttgart, AR, was meant to determine whether damage to rice from glyphosate and imazethapyr was influenced by the timing (15, 30, and 45 d after planting) of exposure to herbicides for thiamethoxam-treated and nontreated rice. There was an overall reduction in injury with the use of thiamethoxam, but the reduction in injury was not dependent on the timing of the drift event. Reduction in damage from physical drift of glyphosate and imazethapyr as well as increased yields over the absence of an insecticide seed treatment appear to be an added benefit.