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Around two-thirds of patients with auditory hallucinations experience derogatory and threatening voices (DTVs). Understandably, when these voices are believed then common consequences can be depression, anxiety and suicidal ideation. There is a need for treatment targeted at promoting distance from such voice content. The first step in this treatment development is to understand why patients listen to and believe voices that are appraised as malevolent.
To learn from patients their reasons for listening to and believing DTVs.
Theoretical sampling was used to recruit 15 participants with non-affective psychosis from NHS services who heard daily DTVs. Data were obtained by semi-structured interviews and analysed using grounded theory.
Six higher-order categories for why patients listen and/or believe voices were theorised. These were: (i) to understand the voices (e.g. what is their motive?); (ii) to be alert to the threat (e.g. prepared for what might happen); (iii) a normal instinct to rely on sensory information; (iv) the voices can be of people they know; (v) the DTVs use strategies (e.g. repetition) to capture attention; and (vi) patients feel so worn down it is hard to resist the voice experience (e.g. too mentally defeated to dismiss comments). In total, 21 reasons were identified, with all participants endorsing multiple reasons.
The study generated a wide range of reasons why patients listen to and believe DTVs. Awareness of these reasons can help clinicians understand the patient experience and also identify targets in psychological intervention.
The term ‘neurogenic’ bladder is non-specific and applies to any lower urinary tract (LUT) dysfunction which is a consequence of neurological disease. A neurogenic bladder can result in disruption of storage and voiding functions of the LUT depending on the associated neurological pathology, which often (but not always) leads to the LUT symptoms and requires prompt evaluation. Urodynamic testing is frequently undertaken to evaluate such patients, as their disease or injury to the nervous system can have profound consequence. The sequelae of neurological LUT dysfunction can include chronic urinary infection, formation of urinary tract calculi, incontinence, vesico-ureteric reflux, acute kidney injury and chronic kidney disease. There is, therefore, a low threshold for urodynamic investigation within this patient group.
According to the International Continence Society (ICS) (2016), cystometry is the continuous fluid filling of the bladder via a transurethral catheter (or other route, e.g. suprapubic or mitrofanoff), with at least intravesical and abdominal pressure measurements and display of detrusor pressure, including cough (stress) testing. Cystometry ends with ‘permission to void’ or with incontinence of the total bladder content .
Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.
Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.
Urine collection methodologies were developed within home settings.
Different cohorts of free-living volunteers.
Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.
This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
Systematic, in-depth exploration of news media coverage of aggression and older adults remains sparse, with little attention to how and why particular frames manifest in coverage across differing settings and relationships. Frame analysis was used to analyze 141 English-language Canadian news media articles published between 2008 and 2019. Existing coverage tended towards stigmatizing, fear-inducing, and biomedical framings of aggression, yet also reflected and reinforced ambiguity, most notably around key differences between settings and relations of care. Mainstream news coverage reflects tensions in public understandings of aggression and older adults (e.g., as a medical or criminal issue), reinforced in particular ways because of the nature of news reporting. More nuanced coverage would advance understanding of differences among settings, relationships, and types of actions, and of the need for multifaceted prevention and policy responses based on these differences.
OBJECTIVES/GOALS: The goal of this project is to identify new therapeutic targets and biomarkers to treat or prevent cocaine toxicity by investigating proteomic, transcriptomic and epigenetic signatures of cocaine exposure in human subjects. METHODS/STUDY POPULATION: Cocaine is a highly addictive neurotoxic substance, and it is estimated that 1.9 million Americans are current users of cocaine. To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem dorsolateral prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine-exposed subjects and 17 controls. Future directions for this project include RNAseq and DNA methylation analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF IMPACT: Neuronal signatures found with this analysis can help us understand mechanisms of cognitive decline in long-term cocaine users as well as the acute effects on the brain of cocaine taken in overdose. With this work and future proposed studies, we can discover novel clinical biomarkers for cocaine neurotoxicity in patients with cocaine use disorder and determine readouts for future therapeutic development on cocaine addiction and overdose.
Halting biodiversity loss depends on changing people’s choices and actions. Increasingly, conservationists use approaches based on social marketing to influence people’s behaviour for the benefit of wider society through techniques developed in the business world. We give definitions of the terms and outline when it should be used instead of, or alongside, law-based, education-based and technical intervention-based approaches. We then illustrate the systematic, step-by-step process underpinning social marketing campaigns with an example from the Caribbean, where the number of people taking wild parrots as pets was successfully reduced. This is followed by examples of social marketing from three different conservation contexts: in community-based natural resource management to reduce the spread of aquatic invasive species, in demand reduction for rhino horn products, and in flagship species fundraising to broaden the benefits for biodiversity. We discuss the lessons that relate more broadly to conservation, including the need to acknowledge ethical issues and the difficulties involved in changing behaviour and the importance of identifying target audiences and evaluating campaigns.
Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.
Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).
Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.
Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.
To assess whether a community water service is associated with the frequency of sugar-sweetened beverages (SSB) consumption, obesity, or perceived health status in rural Alaska.
We examined the cross-sectional associations between community water access and frequency of SSB consumption, body mass index categories, and perceived health status using data from the 2013 and 2015 Alaska Behavioral Risk Factor Surveillance System (BRFSS). Participants were categorized by zip code to ‘in-home piped water service’ or ‘no in-home piped water service’ based on water utility data. We evaluated the univariable and multivariable (adjusting for age, household income and education) associations between water service and outcomes using log-linear survey-weighted generalized linear models.
Rural Alaska, USA.
Eight hundred and eighty-seven adults, aged 25 years and older.
In unadjusted models, participants without in-home water reported consuming SSB more often than participants with in-home water (1·46, 95 % CI: 1·06, 2·00). After adjustment for potential confounders, the effect decreased but remained borderline significant (1·29, 95 % CI: 1·00, 1·67). Obesity was not significantly associated with water service but self-reported poor health was higher in those communities without in-home water (1·63, 95 % CI: 1·05, 2·54).
Not having access to in-home piped water could affect behaviours surrounding SSB consumption and general perception of health in rural Alaska.
To test the effect of a behavioural economics intervention in two food pantries on the nutritional quality of foods available at the pantries and the foods selected by adults visiting food pantries.
An intervention (SuperShelf) was implemented in two food pantries (Sites A and B), with two other pantries (Sites C and D) serving as a control for pantry outcomes. The intervention aimed to increase the amount and variety of healthy foods (supply), as well as the appeal of healthy foods (demand) using behavioural economics strategies. Assessments included baseline and 4-month follow-up client surveys, client cart inventories, pantry inventories and environmental assessments. A fidelity score (range 0–100) was assigned to each intervention pantry to measure the degree of implementation. A Healthy Eating Index-2010 (HEI-2010) score (range 0–100) was generated for each client cart and pantry.
Four Minnesota food pantries, USA.
Clients visiting intervention pantries before (n 71) and after (n 70) the intervention.
Fidelity scores differed by intervention site (Site A=82, Site B=51). At Site A, in adjusted models, client cart HEI-2010 scores increased on average by 11·8 points (P<0·0001), whereas there was no change at Site B. HEI-2010 pantry environment scores increased in intervention pantries (Site A=8 points, Site B=19 points) and decreased slightly in control pantries (Site C=−4 points, Site D=−3 points).
When implemented as intended, SuperShelf has the potential to improve the nutritional quality of foods available to and selected by pantry clients.
The English auxiliary system exhibits many lexical exceptions and subregularities, and considerable dialectal variation, all of which are frequently omitted from generative analyses and discussions. This paper presents a detailed, movement-free account of the English Auxiliary System within Sign-Based Construction Grammar (Sag 2010, Michaelis 2011, Boas & Sag 2012) that utilizes techniques of lexicalist and construction-based analysis. The resulting conception of linguistic knowledge involves constraints that license hierarchical structures directly (as in context-free grammar), rather than by appeal to mappings over such structures. This allows English auxiliaries to be modeled as a class of verbs whose behavior is governed by general and class-specific constraints. Central to this account is a novel use of the feature aux, which is set both constructionally and lexically, allowing for a complex interplay between various grammatical constraints that captures a wide range of exceptional patterns, most notably the vexing distribution of unstressed do, and the fact that Ellipsis can interact with other aspects of the analysis to produce the feeding and blocking relations that are needed to generate the complex facts of EAS. The present approach, superior both descriptively and theoretically to existing transformational approaches, also serves to undermine views of the biology of language and acquisition such as Berwick et al. (2011), which are centered on mappings that manipulate hierarchical phrase structures in a structure-dependent fashion.
Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings.
Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review.
Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use.
Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible.
Alteplase is an effective treatment for ischaemic stroke patients, and it is widely available at all primary stroke centres. The effectiveness of alteplase is highly time-dependent. Large tertiary centres have reported significant improvements in their door-to-needle (DTN) times. However, these same improvements have not been reported at community hospitals.
Red Deer Regional Hospital Centre (RDRHC) is a community hospital of 370 beds that serves approximately 150,000 people in their acute stroke catchment area. The RDRHC participated in a provincial DTN improvement initiative, and implemented a streamlined algorithm for the treatment of stroke patients. During this intervention period, they implemented the following changes: early alert of an incoming acute stroke patient to the neurologist and care team, meeting the patient immediately upon arrival, parallel work processes, keeping the patient on the Emergency Medical Service stretcher to the CT scanner, and administering alteplase in the imaging area. Door-to-needle data were collected from July 2007 to December 2017.
A total of 289 patients were treated from July 2007 to December 2017. In the pre-intervention period, 165 patients received alteplase and the median DTN time was 77 minutes [interquartile range (IQR): 60–103 minutes]; in the post-intervention period, 104 patients received alteplase and the median DTN time was 30 minutes (IQR: 22–42 minutes) (p < 0.001). The annual number of patients that received alteplase increased from 9 to 29 in the pre-intervention period to annual numbers of 41 to 63 patients in the post-intervention period.
Community hospitals staffed with community neurologists can achieve median DTN times of 30 minutes or less.
Based on the data from the Next Generation Virgo cluster Survey (NGVS), we statistically study the photometric properties of globular clusters (GCs), ultra-compact dwarfs (UCDs) and dwarf nuclei in the Virgo core (M87) region. We found an obvious negative color (g - z) gradient in GC system associate with M87, i.e. GCs in the outer regions are bluer. However, such color gradient does not exist in UCD system, neither in dwarf nuclei system around M87. In addition, we found that many UCDs are surrounded by extended, low surface brightness envelopes. The dwarf nuclei and UCDs show different spatial distributions from GCs, with dwarf nuclei and UCDs (especially for the UCDs with visible envelopes) lying at larger distances to the Virgo center. These results support the view that UCDs (at least for a fraction of UCDs) are more tied to dwarf nuclei than to GCs.
The hypovitaminosis D kyphotic pig provides a reliable model to study the initiation of bone lesions caused by maternal vitamin D (D) deficiencies. Matrix metalloproteinases (MMP; specifically, MMP9 and MMP13) and vascular endothelial growth factor (VEGF) are important in endochondral ossification and are potentially regulated by D. Fibroblast growth factor 23 (FGF23) is interrelated with D homoeostasis and bone mineralisation. Relative mRNA expression of MMP9, MMP13, VEGF and FGF23 was measured in pig femur and vertebra. Sows (n 37) were fed diets with 0 (−D), 8·125 (+D) or 43·750 (++D) µg D3/kg throughout gestation and lactation. At weaning (3 weeks), pigs were fed diets with 0 (−D) or 7·0 (+D) µg D3/kg, each with 75 and 95 % (LCaP) or 150 and 120 % (HCaP) of the Ca and P requirements. Pigs at birth (n 27), 3 weeks (n 27) and after the nursery period (7 weeks; n 72) were euthanised for analysis. At 3 weeks, femur MMP9 expression of pigs produced by +D or ++D sows was reduced (P<0·05) to 0·5-fold and VEGF expression to 0·4-fold compared with pigs from –D sows. At 7 weeks, MMP9 expression was reduced (P<0·05) to 0·45-fold in femur and 0·58-fold in vertebra from pigs produced by +D or ++D sows compared with pigs from −D sows. Pig femur VEGF expression was reduced to 0·75-fold in pigs produced by ++D sows. MMP9 and VEGF mRNA expression offer potential markers for the initiation of bone lesions in the hypovitaminosis D kyphotic pig model.