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Customer churn, which insurance companies use to describe the non-renewal of existing customers, is a widespread and expensive problem in general insurance, particularly because contracts are usually short-term and are renewed periodically. Traditionally, customer churn analyses have employed models which utilise only a binary outcome (churn or not churn) in one period. However, real business relationships are multi-period, and policyholders may reside and transition between a wider range of states beyond that of the simply churn/not churn throughout this relationship. To better encapsulate the richness of policyholder behaviours through time, we propose multi-state customer churn analysis, which aims to model behaviour over a larger number of states (defined by different combinations of insurance coverage taken) and across multiple periods (thereby making use of readily available longitudinal data). Using multinomial logistic regression (MLR) with a second-order Markov assumption, we demonstrate how multi-state customer churn analysis offers deeper insights into how a policyholder’s transition history is associated with their decision making, whether that be to retain the current set of policies, churn, or add/drop a coverage. Applying this model to commercial insurance data from the Wisconsin Local Government Property Insurance Fund, we illustrate how transition probabilities between states are affected by differing sets of explanatory variables and that a multi-state analysis can potentially offer stronger predictive performance and more accurate calculations of customer lifetime value (say), compared to the traditional customer churn analysis techniques.
There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS.
This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS.
Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.
We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS.
Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance.
DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp
School violence is a significant social concern. To better understand its sources, a comprehensive meta-analysis of the school violence and victimization literature was undertaken. Across 761 studies, the relative effects of 30 different individual, school, and community level correlates were assessed (8,790 effect size estimates). Violence and victimization were conceptualized broadly to include various forms of aggression and crime at school. The results revealed that the strongest correlates of school violence perpetration were antisocial behavior, deviant peers, antisocial attitudes, victimization, and peer rejection; and that the strongest correlates of school victimization were prior/other victimization, social competence, risk avoidance, antisocial behavior, and peer rejection. Extracurricular activities and school security devices had among the weakest associations in the meta-analysis, and several traditional criminological predictors did not perform well in the school context. We conclude with recommendations for theory, future research, and policy.
In this chapter, we provide a historical and a contemporary overview of the hearing brain. We will review how various brain-imaging methods are employed to study how sounds and meanings are represented in the brain. These studies have provided the foundation from which network models of the brain are built. We will conclude with a discussion of the practical aspects of the neuroscience of language, such as how it will further our understanding of the brain and lead to clinical applications.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
To evaluate whether a series of quality improvement interventions to promote safe perioperative use of cephalosporins in penicillin-allergic patients improved use of first-line antibiotics and decreased costs.
Before-and-after trial following several educational interventions.
Academic medical center.
This study included patients undergoing a surgical procedure involving receipt of a perioperative antibiotic other than a penicillin or carbapenem between January 1, 2017, and August 31, 2019. Patients with and without a penicillin allergy label in their electronic medical record were compared with respect to the percentage who received a cephalosporin and average antibiotic cost per patient.
A multidisciplinary team from infectious diseases, allergy, anesthesiology, surgery, and pharmacy surveyed anesthesiology providers about their use of perioperative cephalosporins in penicillin-allergic patients. Using findings from that survey, the team designed a decision-support algorithm for safe utilization and provided 2 educational forums to introduce this algorithm, emphasizing the safety of cefazolin or cefuroxime in penicillin-allergic patients without history of a severe delayed hypersensitivity reaction.
The percentage of penicillin-allergic patients receiving a perioperative cephalosporin improved from ∼34% to >80% following algorithm implementation and the associated educational interventions. This increase in cephalosporin use was associated with a ∼50% reduction in antibiotic cost per penicillin-allergic patient. No significant adverse reactions were reported.
An educational antibiotic stewardship intervention produced a significant change in clinician behavior. A simple intervention can have a significant impact, although further study is needed regarding whether this response is sustained and whether an educational intervention is similarly effective in other healthcare systems.
Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.
Mycoprotein consumption has been shown to improve acute postprandial glycaemic control and decrease circulating cholesterol concentrations. We investigated the impact of incorporating mycoprotein into the diet on insulin sensitivity (IS), glycaemic control and plasma lipoprotein composition. Twenty healthy adults participated in a randomised, parallel-group trial in which they consumed a 7 d fully controlled diet where lunch and dinner contained either meat/fish (control group, CON) or mycoprotein (MYC) as the primary source of dietary protein. Oral glucose tolerance tests were performed pre- and post-intervention, and 24 h continuous blood glucose monitoring was applied throughout. Fasting plasma samples were obtained pre- and post-intervention and were analysed using quantitative, targeted NMR-based metabonomics. There were no changes within or between groups in blood glucose or serum insulin responses, nor in IS or 24 h glycaemic profiles. No differences between groups were found for 171 of the 224 metabonomic targets. Forty-five lipid concentrations of different lipoprotein fractions (VLDL, LDL, intermediate-density lipoprotein and HDL) remained unchanged in CON but showed a coordinated decrease (7–27 %; all P < 0·05) in MYC. Total plasma cholesterol, free cholesterol, LDL-cholesterol, HDL2-cholesterol, DHA and n-3 fatty acids decreased to a larger degree in MYC (14–19 %) compared with CON (3–11 %; P < 0·05). Substituting meat/fish for mycoprotein twice daily for 1 week did not modulate whole-body IS or glycaemic control but resulted in changes to plasma lipid composition, the latter primarily consisting of a coordinated reduction in circulating cholesterol-containing lipoproteins.
The normal adult MV area is 4–6 cm2. Unlike other heart valves, the MV consists of two asymmetric leaflets. The aortic (anterior) leaflet makes up 65% of the valve area but its base forms only 35% of the circumference. The mural (posterior) leaflet usually consists of three main scallops, although there may be up to five. The leaflets are joined at the anterolateral and posteromedial ends of the commissure. The aortic MV leaflet shares the same fibrous attachment as the non-coronary cusp of the AV.
The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT.
We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (<6 hours from onset) and late (≥6 hours from onset or last time seen normal) window groups. Incidence of symptomatic hemorrhagic transformations (sHTs) at 24 hours and 3-month modified Rankin scores (mRSs) were compared.
During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15–23] vs. late: 17 [13–21]), as were median ASPECT scores (early: 9 [8–10] vs. late: 9 [7–9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0–2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76).
NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.
This paper considers actuator redundancy management for a redundant multirotor Unmanned Aerial Vehicle (UAV) under actuators failures. Different approaches are proposed: using robust control (passive fault tolerance), and reconfigurable control (active fault tolerance). The robust controller is designed using high-order super-twisting sliding mode techniques, and handles the failures without requiring information from a Fault Detection scheme. The Active Fault-Tolerant Control (AFTC) is achieved through redistributing the control signals among the healthy actuators using reconfigurable multiplexing and pseudo-inverse control allocation. The Fault Detection and Isolation problem is also considered by proposing model-based and model-free modules. The proposed techniques are all implemented on a coaxial octorotor UAV. Different experiments with different scenarios were conducted for the validation of the proposed strategies. Finally, advantages, disadvantages, application considerations and limitations of each method are examined through quantitative and qualitative studies.
Retinoblastoma is the most common primary intraocular tumor of childhood with >95% survival rates in the US. Traditional therapy for retinoblastoma often included enucleation (removal of the eye). While much is known about the visual, physical, and cognitive ramifications of enucleation, data are lacking about survivors' perception of how this treatment impacts overall quality of life.
Qualitative analysis of an open-ended response describing how much the removal of an eye had affected retinoblastoma survivors' lives and in what ways in free text, narrative form.
Four hundred and four retinoblastoma survivors who had undergone enucleation (bilateral disease = 214; 52% female; mean age = 44, SD = 11) completed the survey. Survivors reported physical problems (n = 205, 50.7%), intrapersonal problems (n = 77, 19.1%), social and relational problems (n = 98, 24.3%), and affective problems (n = 34, 8.4%) at a mean of 42 years after diagnosis. Three key themes emerged from survivors' responses; specifically, they (1) continue to report physical and intrapersonal struggles with appearance and related self-consciousness due to appearance; (2) have multiple social and relational problems, with teasing and bullying being prominent problems; and (3) reported utilization of active coping strategies, including developing more acceptance and learning compensatory skills around activities of daily living.
Significance of results
This study suggests that adult retinoblastoma survivors treated with enucleation continue to struggle with a unique set of psychosocial problems. Future interventions can be designed to teach survivors more active coping skills (e.g., for appearance-related issues, vision-related issues, and teasing/bullying) to optimize survivors' long-term quality of life.
Masses have been computed for the white dwarfs (WDs) in eclipsing, mass exchange (symbiotic), WD–red giant (RG) binaries by using single-lined spectroscopic orbits, orbital inclinations, and the RG masses. Inclinations have been measured for 13 eclipsing symbiotic binaries. Using Gaia data the mass of the RG can be found from evolutionary tracks. Since the WD evolved from the more massive star in the binary, the WD should be more massive than predicted from the mass of the current RG. Typically the WD has a lower mass than expected implying a previous mass exchange stage for these systems.
Aquaculture is one of the fastest-growing food production sectors in many low-income and food-deficit countries with aquatic ecozones. Yet its specific impact on nutrition and livelihood in local communities, where commercial and/or export-orientated aquaculture activities are developed, is largely unknown.
The present narrative and argumentative review aims to provide an overview of our current understanding of the connections between aquaculture agroecosystems, local and national fish production, fish consumption patterns and nutrition and health outcomes.
The agroecological dynamic in a coastal-estuarine zone, where the aquatic environment ranges from fully saline to freshwater, is complex, with seasonal and annual fluctuations in freshwater supply creating a variable salinity gradient which impacts on aquatic food production and on food production more generally. The local communities living in these dynamic aquatic ecozones are vulnerable to poverty, poor diet and health, while these ecosystems produce highly valuable and nutritious aquatic foods. Policies addressing the specific challenges of risk management of these communities are limited by the sectoral separation of aquatic food production – the fisheries and aquaculture sector, the broader food sector – and public health institutions.
Here we provide an argument for the integration of these factors to improve aquaculture value chains to better address the nutritional challenges in Bangladesh.
This paper deals with the problem of fault-tolerant control (FTC) for redundant multirotor unmanned aerial vehicles (UAVs) subject to actuators failures. A fuzzy logic approach is used to solve the constrained control allocation problem by adjusting the components of the multiplexing vector once a motor failure is detected. This fuzzy logic allocation problem is tuned using the Bacterial Foraging Algorithm (BFA), a powerful bio-inspired optimisation technique. The effectiveness of this approach is illustrated through real experimental application to a hexarotor UAV, where up to two motors failures are considered.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
The heat transfer properties of the organic molecular crystal α-RDX were studied using three phonon scattering based thermal conductivity models. It was found that the widely used Peierls-Boltzmann model for thermal transport in crystalline materials breaks down for α-RDX. We show this breakdown is due to a large degree of anharmonicity that leads to a dominance of diffusive-like carriers. Despite being developed for disordered systems, the Allen-Feldman theory for thermal conductivity actually gives the best description of thermal transport. This is likely because diffusive carriers contribute to over 95% of the thermal conductivity in α-RDX. The dominance of diffusive carriers is larger than previously observed in other fully ordered crystalline systems. These results indicate that van der Waals bonded organic crystalline solids conduct heat in a manner more akin to amorphous materials than simple atomic crystals.
OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.
The commissioning and operation of apparatus for neutron diffraction at simultaneous high temperatures and pressures is reported. The basic design is based on the Paris-Edinburgh cell using opposed anvils, with internal heating. Temperature is measured using neutron radiography. The apparatus has been shown in both on-line and off-line tests to operate to a pressure of 7 GPa and temperature of 1700°C. The apparatus has been used in a neutron diffraction study of the crystal structure of deuterated brucite, and results for 520°C and 5.15 GPa are presented. The diffraction data that can be obtained from the apparatus are of comparable quality to previous high-pressure studies at ambient temperatures, and are clearly good enough for Rietveld refinement analysis to give structural data of reasonable quality.