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Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
Prolonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators.
Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV.
For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, >4.54 log10, and >4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators.
With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
The Hawkesbury Sandstone (Hawkesbury Series, Sydney Basin) on the southeastern coast of New South Wales, Australia, preserves a depauperate but important vertebrate tetrapod body-fossil record from the Early and Middle Triassic. As with many fossil sites around the world, the ichnological record has helped to shed light on the paleoecology of this interval. Herein, we investigate historical reports of a trackway pertaining to a putative short-tailed reptile found at Berowra Creek in the 1940s. Reinvestigation of the surviving track-bearing slabs augmented by archival photographs of the complete trackway, suggests that these impressions, which consist primarily of didactyl tracks (plus less common monodactyl and tridactyl traces), represent the earliest example of a swimming tetrapod found in Australia. Another isolated specimen (possibly from a nearby locality at Annangrove) appears to represent similar didactyl swim traces of a second, larger individual. Although the identities of the trackmakers are unknown, the Berowra Creek individual had an estimated body length of between ~80 cm (short-coupled) and 1.35 m (long-coupled), and produced the subaqueous trackway while travelling upslope (against the current) on a sandbar within a braided river system of the Hawkesbury Sandstone. These trackways partially resemble amphibian swim traces in the so-called Batrachichnus C Lunichnium continuum, but appear to represent a unique locomotion trace. This reanalysis of the Berowra Creek trackway provides insight into the locomotion of tetrapods of the Triassic Hawkesbury Series, which remains a poorly understood aspect of their life history.
Background: Telemedicine has been defined as the use of technology to provide healthcare when the provider and patient are geographically separated. Use of telemedicine to meet the needs of specific populations has become increasingly common across Canada. The current study employs the Ontario Telemedicine Network (OTN) to connect the emergency departments of a community hospital system and a pediatric tertiary care hospital. OTN functions through a two-way video conferencing system, allowing physicians at the tertiary site to see and hear the patient being treated in the community hospitals. Aim Statement: The aim of this project is to ensure essential care is provided to CTAS 1 and 2 pediatric patients who present to Niagara Health emergency departments, to increase the number of appropriate patient transfers. Measures & Design: Data for this project include a) description of common diagnoses, b) time of call, c) occurrence of transfers, and d) professional perceptions of the technology. A descriptive design was used together with the implementation of quality improvement cycles as the intervention occurred. Quality improvement methodologies including plan-do-study-act (PDSA) cycles ensured continuous improvement to the process of OTN use and therefore patient safety throughout the study. Evaluation/Results: Since the intervention was employed on December 17, 2018 there have been a total of 19 cases for which 4 transfers were requested. Changes to the process were made including the addition of weekly technology tests and feedback to health professionals involved to garner further support for the use. Results have indicated that seizure was the most common diagnosis, accounting for 37% of cases. The majority of calls were placed after 19:00 hours with no calls being placed between 24:00 and 10:00. Discussion/Impact: Healthcare providers had positive perceptions of the technology agreeing that decision making between on-site and remote teams was timely and collaborative, as well as that patient care and outcomes were improved with its use. The results of this study will be used to determine the benefits of employing telemedicine in the emergency departments of other hospital systems.
The combination of clozapine and other potentially leukopenic drugs may pose a greater risk for neutropenia. However, neutropenia may not always be due to clozapine. When adding potentially leukopenic drugs, clinicians should look for possible alternatives especially as clozapine is often a drug used as the last resort in treatment refractory schizophrenia.
Topiramate is an antiepileptic agent, which is being investigated as a mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and type II diabetes mellitus received topiramate treatment in combination with antipsychotics and valproate or carbamazepine. In addition to improved mood stability, these individuals lost between 16 to 20.5% of their pre-topiramate body weight and also achieved significant glycemic control.
“Folie à deux” is also known in the ICD-10 as Induced Delusional Disorder. A subtype is “folie imposee” where the primary individual holds delusional beliefs shared by a secondary individual. When the delusional beliefs of the primary individual cease it is observed that the beliefs of the secondary individual also disappear. Mr A was a 36 year old Caucasian male presenting with an array of psychotic symptoms centred on a task which involved finding an energy source at the centre of the earth. Mrs A was highly resistant to his treatment and further investigation revealed a case of folie à deux.
To demonstrate the phenomenon of folie à deux.
Individual and combined interviews were held with Mr and Mrs A where the psychotic symptoms were discussed. A comprehensive study of Mr A's past and current psychopathology was also undertaken.
Mrs A shared the delusions of her partner and was strongly against treatment as it would nullify his delusions rendering him incapable of completing his task. Once treatment was facilitated, Mr A experienced a drop from his unusually high levels of energy which reflected an equal and immediate drop in energy levels of his partner which led her to further discourage him from medication. When Mr A's delusional beliefs lifted, it was apparent that his partner no longer held the same delusional beliefs.
We concluded this case fulfilled ICD-10 and DSM IV criteria for a shared delusional disorder (folie à deux) with specific sub-type “folie imposee”.
Constituting 2% of the population, PWDID are a vulnerable group with a higher prevalence of mental disorders than the general population. ICD diagnostic criteria often rely on adequate cognitive functioning and hence diagnosis of mental disorders in PWDID can be difficult, consequently leading to inequity of treatment, prognosis and stigma. Our study critically analysed the available evidence base and explored the feasibility of applying modified diagnostic criteria within the context of cumulative iterative iteration. We present the outcome using diagnosis of DID and anxiety disorder as examples.
Address current shortcomings in ICD classification regarding PWDID by contributing effectively to the WHO ICD-11 consultation process in collaboration with international stakeholders.
Facilitate accessibility of ICD-11 criteria for diagnosis of mental disorders capable of engendering robust evidence based epidemiological data and healthcare in PWDID.
We evaluated current evidence via a systematic literature search utilising PRISMA guidelines and developed pragmatic guidelines to adapt ICD diagnostic criteria in PWDID. A brief screener [Glasgow Level of Ability and Development Scale (GLADs)] for detecting DID was also studied internationally within the context of clinical utility (n = 136).
The evidence base relating to mental disorders in PWDID is poor, significantly hampered by difficulties in applicability of diagnostic criteria. The GLADs appears to be a promising screening tool with good clinical utility for detecting disorders of intellectual development (DID) particularly where resources are scarce.
Pragmatic modifications to ICD-11 diagnostic criteria and the GLADS tool facilitates its clinical utility for PWDID and contributes significantly to enhancing research based evidence, and, ultimately their health access and well-being.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Silicon carbide (SiC) is ideally suitable as a sensor material in harsh environments. Despite the brittleness in the macroscopic scale, plasticity in SiC is observed at small component length-scales. Previous nanoindentation based study combining experiment and numerical approaches of single-crystal 6H-SiC has shown that slip activation is rather complex, and that non-basal slip could potentially dominate the plastic deformation behaviour. In this study, we investigated the local deformation response evolution of shear strain directly under and in the vicinity of the indenter tip. The results show the pyramidal slip families contribute significantly to the deformation process.
We identify mechanisms through which open-loop control of thermoacoustic instability is achieved in a laminar combustor and characterize them using synchronization theory. The thermoacoustic system comprises two nonlinearly coupled damped harmonic oscillators – acoustic and unsteady heat release rate (HRR) field – each possessing different eigenfrequencies. The frequency of the preferred mode of HRR oscillations is less than the third acoustic eigenfrequency where thermoacoustic instability develops. We systematically subject the limit-cycle oscillations to an external harmonic forcing at different frequencies and amplitudes. We observe that forcing at a frequency near the preferred mode of the HRR oscillator leads to a greater than 90 % decrease in the amplitude of the limit-cycle oscillations through the phenomenon of asynchronous quenching. Concurrently, there is a resonant amplification in the amplitude of HRR oscillations. Further, we show that the flame dynamics plays a key role in controlling the frequency at which quenching is observed. Most importantly, we show that forcing can cause asynchronous quenching either by imposing out-of-phase relation between pressure and HRR oscillations or by inducing period-2 dynamics in pressure oscillations while period-1 in HRR oscillations, thereby causing phase drifting between the two subsystems. In each of the two cases, acoustic driving is very low and hence thermoacoustic instability is suppressed. We show that the characteristics of forced synchronization of the pressure and HRR oscillations are significantly different. Thus, we find that the simultaneous characterization of the two subsystems is necessary to quantify completely the nonlinear response of the forced thermoacoustic system.
Population Decline in New Ireland, Papua New Guinea
In this chapter I discuss my own research and clinical experiences in Papua New Guinea, where I worked between 1947 and 1974 and had subsequent visits up until 1987, studying the relationship between community infertility and the prevalence of gonorrhea. Its particular significance for this volume is that this was the first time that a rigorous and systematic clinical and medical examination had been performed on a population suffering from widespread infertility to determine whether psychosocial factors or STIs—and specifically gonorrhea—were the source of the community's infertility. Gonorrhea was, indeed, found to be the cause in the Tabar Islands, and the hypothesis was confirmed by a concurrent program of universal penicillin distribution throughout the Tabar population resulting in a remarkable rebound in fertility and a reversal of the population decline.
I was born in New Zealand, and through to my graduation in medicine had regular contact with Pacific Islanders and missionaries. However, my engagement with New Guinea research began by chance. Medical interns without a family medical background were and are influenced by the role models presented by their teachers. My future career was subtly influenced by Sir John Cleland, professor of pathology, who had studied and written extensively on anthropology and Australian Aboriginal health. He offered me a medical research position in Arnhem Land, but I saw medical positions available in the Territory of Papua and New Guinea. In August 1947 I became the thirteenth medical officer to be appointed after World War II, to a country where the fortunate were receiving medical care from barefoot orderlies, but many others had no medical contact.
There were no numerators or denominators to measure the impact of endemic and introduced diseases on the inhabitants of this tropical environment. In 1948, as medical officer at Sohano on Buka Island, a large island just north of Bougainville Island, I set about establishing medical records and genealogies of two Buka communities: Lemankoa, a large village of the Haku tribe on the northwest coast; and villages of the inland Solas people along the Gagan River. I had access to the birth, death, and marriage records collected by Catholic missionaries since 1915, which were preserved in bound volumes that had been wrapped in banana leaves and hidden in caves during the war.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
We investigated human understanding of different network visualizations in a large-scale online experiment. Three types of network visualizations were examined: node-link and two different sorting variants of matrix representations on a representative social network of either 20 or 50 nodes. Understanding of the network was quantified using task time and accuracy metrics on questions that were derived from an established task taxonomy. The sample size in our experiment was more than an order of magnitude larger (N = 600) than in previous research, leading to high statistical power and thus more precise estimation of detailed effects. Specifically, high statistical power allowed us to consider modern interaction capabilities as part of the evaluated visualizations, and to evaluate overall learning rates as well as ambient (implicit) learning. Findings indicate that participant understanding was best for the node-link visualization, with higher accuracy and faster task times than the two matrix visualizations. Analysis of participant learning indicated a large initial difference in task time between the node-link and matrix visualizations, with matrix performance steadily approaching that of the node-link visualization over the course of the experiment. This research is reproducible as the web-based module and results have been made available at: https://osf.io/qct84/.
Trait-specific characterization of rice landraces has significant potential for germplasm management, varietal identification and mining of novel gene/allele for various traits. In the current study, we have characterized 98 unique rice landraces collected from coastal regions of India, affected by submergence and salinity, based on Sub1 and Saltol quantitative trait loci (QTL) linked microsatellite markers. Among these genotypes, four genotypes (IC536558, IC536559, IC536604 and IC536604-1) collected from Kerala and two genotypes (AC34902 and IC324589) collected from West Bengal were identified with tolerance to submergence and salinity stress. A high level of genetic diversity of He = 0.349 and 0.529 at Sub1 and Saltol QTL region was detected by QTL-linked microsatellite markers, respectively. At Sub1 region one genotype, AC34902, was detected with maximum allelic similarity with FR13A, a known submergence tolerant variety. Besides, five genotypes (IC211188-1, IC536604-1, IC536604, IC536558 and IC536559) showed comparatively close genetic relationship with the salt tolerant variety FL478 for Saltol QTL and were clustered together in the neighbour joining dendrogram. Considering the haplotype structure, five genotypes (IC203801, IC203778, IC324584, IC413608 and IC413638) were identified which did not contain any common allele similar to FR13A but were still tolerant to submergence. These individuals need further characterization for identification of new alleles responsible for their tolerance.
Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.
We aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response.
Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety.
Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28–3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68–16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response.
Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects.
OBJECTIVES/SPECIFIC AIMS: We hypothesized that CXCL12, as a biased dimer variant or secreted at dimer-dominant concentrations, would influence PDAC growth and progression. METHODS/STUDY POPULATION: PDAC cells were genetically manipulated to express dimer-promoting levels of CXCL12. These cells were studied in vitro or orthotopically implanted into the mouse pancreas for in vivo studies. As a second approach, recombinant wild-type or engineered CXCL12 monomer or dimer proteins were applied to cells in culture or administered intra-peritoneal to study the effects on tumor growth. RESULTS/ANTICIPATED RESULTS: Mice engrafted with CXCL12-expressing cells had a better survival rate, delayed tumor growth and smaller tumors. Tumors from these mice had significantly less proliferation, measured by Ki-67 staining. In vitro analysis of CXCL12-expressing cells showed decreased viability and growth rates. Percent of cells in the cell cycle G2 phase was also decreased, suggesting cell cycle progression blockade. Viability of human PDAC cells dose-dependently declined upon wild-type CXCL12 treatment, with the non-motile dimer-dominant dose (1000 nM) exhibiting maximal effect. Treatment in an allogeneic mouse model of PDAC with locked-dimer CXCL12, but not wild-type, reduced tumor burden. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results support the notion that biased CXCL12 signaling may be therapeutically exploited to limit pancreatic cancer progression.