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Matrix positivity is a central topic in matrix theory: properties that generalize the notion of positivity to matrices arose from a large variety of applications, and many have also taken on notable theoretical significance, either because they are natural or unifying. This is the first book to provide a comprehensive and up-to-date reference of important material on matrix positivity classes, their properties, and their relations. The matrix classes emphasized in this book include the classes of semipositive matrices, P-matrices, inverse M-matrices, and copositive matrices. This self-contained reference will be useful to a large variety of mathematicians, engineers, and social scientists, as well as graduate students. The generalizations of positivity and the connections observed provide a unique perspective, along with theoretical insight into applications and future challenges. Direct applications can be found in data analysis, differential equations, mathematical programming, computational complexity, models of the economy, population biology, dynamical systems and control theory.
Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ~0.1 mm d−1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.
Quantifying the rate of wave attenuation in sea ice is key to understanding trends in the Antarctic marginal ice zone extent. However, a paucity of observations of waves in sea ice limits progress on this front. We deployed 14 waves-in-ice observation systems (WIIOS) on Antarctic sea ice during the Polynyas, Ice Production, and seasonal Evolution in the Ross Sea expedition (PIPERS) in 2017. The WIIOS provide in situ measurement of surface wave characteristics. Two experiments were conducted, one while the ship was inbound and one outbound. The sea ice throughout the experiments generally consisted of pancake and young ice <0.5 m thick. The WIIOS survived a minimum of 4 d and a maximum of 6 weeks. Several large-wave events were captured, with the largest recorded significant wave height over 9 m. We find that the total wave energy measured by the WIIOS generally decays exponentially in the ice and the rate of decay depends on ice concentration.
The Ross Sea is known for showing the greatest sea-ice increase, as observed globally, particularly from 1979 to 2015. However, corresponding changes in sea-ice thickness and production in the Ross Sea are not known, nor how these changes have impacted water masses, carbon fluxes, biogeochemical processes and availability of micronutrients. The PIPERS project sought to address these questions during an autumn ship campaign in 2017 and two spring airborne campaigns in 2016 and 2017. PIPERS used a multidisciplinary approach of manned and autonomous platforms to study the coupled air/ice/ocean/biogeochemical interactions during autumn and related those to spring conditions. Unexpectedly, the Ross Sea experienced record low sea ice in spring 2016 and autumn 2017. The delayed ice advance in 2017 contributed to (1) increased ice production and export in coastal polynyas, (2) thinner snow and ice cover in the central pack, (3) lower sea-ice Chl-a burdens and differences in sympagic communities, (4) sustained ocean heat flux delaying ice thickening and (5) a melting, anomalously southward ice edge persisting into winter. Despite these impacts, airborne observations in spring 2017 suggest that winter ice production over the continental shelf was likely not anomalous.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
OBJECTIVES/GOALS: Initiation of JUUL use by young adults is one of the most significant issues of concern within the debate on vaping. Despite the proliferation of products and the surge in prevalence, no studies have investigated individual-level interventions or prevention strategies for pod-mod use. METHODS/STUDY POPULATION: Participants (N = 947) were young adults (<30 years old) recruited from Amazon’s Mechanical Turk based on smoking (never, former, and current smokers) and JUUL use status (never and current users), resulting in 6 use groups. In a pre-post design, participants completed baseline assessments, were presented with a brief JUUL-specific educational intervention, and completed post-assessment measures. The one-page intervention provided basic information about JUUL and stated that JUUL is harmful to non-smokers but could be beneficial to smokers if they completely switch. Primary outcomes were changes in JUUL knowledge, perceived harmfulness, intentions for future use, and motivation to change. RESULTS/ANTICIPATED RESULTS: Participants (Mage = 26.1) were male (57%) and White (75%). Overall, the intervention increased JUUL-related knowledge, risk perceptions, commitment to quitting, and readiness to quit JUUL (ps<.01). Similarly, participants showed decreased interest in future JUUL use, interest in purchasing JUUL, and interest in future regular use (ps<.01). Non-JUUL users showed decreased interest in initiating JUUL use after viewing the intervention (p<.01). There were significant Time X Group interactions for JUUL-related knowledge (p<.001), with never JUUL/never smokers showing the greatest increase in product knowledge following the intervention. However, no other interaction effects were significant. DISCUSSION/SIGNIFICANCE OF IMPACT: The intervention was effective in increasing knowledge and risk perceptions while reducing intentions for future use. The intervention was most effective in increasing knowledge among non-users, suggesting that brief educational interventions may be useful tools for preventing pod-mod initiation. CONFLICT OF INTEREST DESCRIPTION: Dr. Carpenter has received consulting honoraria from Pfizer. All other authors have no conflicts to disclose.
Antidepressant use has risen x3-5 in Western countries since the early 1990s, outstripping changes in depression incidence or prevalence. This represents a major public health challenge.
Nationally-collected antidepressant data were used to assess the impact of "Doing Well", (DW) a novel depression care programme operating in Renfrewshire, Scotland. "Doing Well" implemented a model of “stepped collaborative care”, practitioner education and significant service redesign. Prescribing was compared for three groups: "DW" (76,000 population; clinical and educational intervention), "DW neighbours” (101,000 population; educational interventions only), and Scotland (no specific intervention).
A national rise in antidepressant prescriptions was stabilised for the "DW" group (graph). Antidepressant cost/item fell by 42% and 40% in both “DW” and “DW neighbours” groups but rose by 8% nationally.
Access to clinical interventions are required to reduce antidepressant prescriptions, but cost savings may be made with educational interventions alone.
Depression is a major public health problem in European countries, and health systems need to ensure access to effective psychological and pharmacological treatments. Research suggests that improvements in depression care require “complex interventions” that implement change in several areas simultaneously.
We describe an observational study of the implementation of a “stepped care” model to provide care for all adults presenting with a new case of depression in a mixed urban-rural area of Scotland with a population of 76,000 people.
A team of 5.2 clinicians provided care for about 1,000 new cases of depression each year. “Guided Self-Help” was the baseline intervention for all patients, supplemented where necessary with pharmacological treatment and Cognitive Behavioural or Interpersonal Therapy.
Service delivery systems were reformed to provide: specialist treatment in primary care settings using primarily non-medical clinicians, comprehensive electronic clinical records, continuous outcome monitoring and intensive investment in staff training and support.
Clinical outcomes (measured by the Personal Health Questionnaire, Social and Work Adjustment Scale and EQ-5D) showed significant improvement despite relatively brief clinician contact (2.5 hours over 4.6 contacts). Savings of more than 50% were made on the antidepressant drug budget. Service user satisfaction ratings were high.
Population needs for depression care can be met using “stepped care” models such as that described above. A randomised controlled study of this approach would be required to fully test the model.
Against a backdrop of poor mental health education in UK schools a group of students from Norwich Medical School have formed a student society called ‘Headucate’ in order to create, deliver and evaluate an educational intervention for adolescents, initially to be delivered in Norfolk schools.
To create an educational intervention that:
Is the length of a standard lesson
Is age appropriate and acceptable
Contains appropriate signposting
Contains content that challenges common myths and replaces them with knowledge
Contains content that encourages empathy and understanding towards those with mental illnesses
Is easily delivered in the same way each time so that its effectiveness can be evaluated
To create an intervention effective at tackling stigma and empowering adolescents to recognise signs of poor mental health and access services appropriately.
Lesson plan created after consultation with psychiatrists, a psychologist, a GP, a university outreach professional, a teacher and secondary school age children, then trialled and revised.
Interactive workshop produced with 5 sections.
1) Myth vs Fact activity that dispels prevalent myths
2) Scenario based activity to demonstrate that mental health is a spectrum
3) An interactive presentation covering the most common mental illnesses and their symptoms
4) An activity focusing on talking to those with mental illnesses, furthering the scenario from the previous activity
5) A question and answer session. Every student leaves with a leaflet containing appropriate signposting.
We have created an educational intervention ready to be delivered and evaluated.
Mental health education is not compulsory in the UK therefore adolescents have very varied experiences despite half of people with mental health illnesses reporting having experienced symptoms by 14 years old. University students are ideal for delivering a relaxed, educational intervention aimed at this age group, providing an opportunity to for them to learn necessary tools for recognising signs of poor mental health and tackle associated stigma.
To expand Headucate's membership, including other disciplines within the University of East Anglia (UEA) and provide core training enabling members to deliver a school-based educational intervention
Recruitment of members has been a multifaceted approach utilising social media sites such as Facebook and the Headucate website, and oncampus events and ‘awareness campaigns’ including several successful evening talks and lectures.
Three training sessions, which include ‘Introduction to Mental Health’, ‘Workshop run-through’ and ‘Child Protection’, have been developed for all members wishing to partake in the delivery of workshops.
We have recruited approximately 300 members since summer 2012; 70 fully paid members in 2012/13 academic year and currently 45 paid members for 2013/14.
A total of 18 members are fully trained and ready to deliver workshops within schools and 17 other members have just one training session remaining.
We are looking forward to delivering our first workshops in October and building on a successful first year. We are confident we can provide workshops for approximately 600 children per year.
Social interactions dysfunctions make up core symptoms of many mental disorders and have been extensively studied through cognitive paradigms gathered under the concept of social cognition. Nevertheless, a growing body of literature have demonstrated that motor coordination is an important feature of these human social interactions but has been little studied in the context of mental diseases.
In this study, we propose to compare the processes of inter-agent coordination in healthy and socially impaired clinical populations (e.g. schizophrenia and social phobia patients).
20 schizophrenia and 20 social phobia patients were compared to 20 healthy subjects using an hand-held pendulum paradigm in intentional and unintentional interpersonal motor coordination, with different leadership conditions. All participants had psychopathological and neuropsychological evaluations.
Our results demonstrated that each group of subject was characterised by specific signature concerning interpersonal motor coordination. More specifically, instability of the coordination and temporal delay between patient and controls revealed that schizophrenia impaired intentional coordination but not spontaneous non-intentional coordination whereas social phobia only affected leader conditions.
Taken altogether, these preliminary results give evidence that motor control through motor coordination behaviours is a fundamental part of social interactions deficits in schizophrenia and social phobia. These results lead us to examine if the evaluation of motor coordination during a social interactions could help to discriminate the deficits in social interactions and to propose specific therapy for their rehabilitation.
This research was supported by an Agence Nationale de la Recherche grant (Project SCAD # ANR-09- BLAN-0405-03).
The symptoms of many mental illnesses often begin during high school. Interventions to improve mental health awareness amongst adolescents may lead to improved outcomes. in the UK unfortunately many schools do not fulfil this need and mental health education is not a compulsory part of the curriculum.
To develop and measure the effectiveness of and educational intervention designed to raise awareness and empower adolescents to recognise signs of poor mental health and access services appropriately.
Evaluate the effectiveness of the intervention through baseline and follow up surveys.
Students at Norwich Medical School collaborated with teachers, psychiatrists and general practitioners to design an educational intervention that aims to tackle stigma and raise awareness of mental health conditions among 13-14 year olds in the hope that they can access services when needed, support those around them and look after their mental health. To evaluate effectiveness of the intervention, a knowledge, attitudes and practices survey that utilises a social distance scale that has been adapted for this age group and will be used to gather baseline and follow up data after six months.
We have developed a one-hour educational intervention delivered by medical students, that uses a variety of teaching techniques to raise awareness of mental health issues. We will start implementation in January 2013 so will have baseline effectiveness results shortly after.
Headucate has the potential to fill an important gap in effectively raising awareness of mental health issues in schools.
Worldwide, early intervention services for young people with recent-onset psychosis have been associated with improvements in outcomes, including reductions in hospitalization, symptoms, and improvements in treatment engagement and work/school participation. States have received federal mental health block grant funding to implement team-based, multi-element, evidence-based early intervention services, now called coordinated specialty care (CSC) in the USA. New York State’s CSC program, OnTrackNY, has grown into a 23-site, statewide network, serving over 1800 individuals since its 2013 inception. A state-supported intermediary organization, OnTrackCentral, has overseen the growth of OnTrackNY. OnTrackNY has been committed to quality improvement since its inception. In 2019, OnTrackNY was awarded a regional hub within the National Institute of Mental Health-sponsored Early Psychosis Intervention Network (EPINET). The participation in the national EPINET initiative reframes and expands OnTrackNY’s quality improvement activities. The national EPINET initiative aims to develop a learning healthcare system (LHS); OnTrackNY’s participation will facilitate the development of infrastructure, including a systematic approach to facilitating stakeholder input and enhancing the data and informatics infrastructure to promote quality improvement. Additionally, this infrastructure will support practice-based research to improve care. The investment of the EPINET network to build regional and national LHSs will accelerate innovations to improve quality of care.
The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.
Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.
At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion.
Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.
DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling the G1 checkpoint or ATR-CHK1-Wee1 pathway controlling the S and G2/M checkpoints. Loss of G1 checkpoint control is common in cancer through TP53, ATM mutations, Rb loss or cyclin E overexpression, providing a stronger rationale for targeting the S/G2 checkpoints. This review will focus on the ATM-CHK2-p53-p21 pathway and the ATR-CHK1-WEE1 pathway and ongoing efforts to target these pathways for patient benefit.