Tracking excited states in wave function optimization using density matrices and variational principles

We present a method for finding individual excited states' energy stationary points in complete active space self-consistent field theory that is compatible with standard optimization methods and highly effective at overcoming difficulties due to root flipping and near-degeneracies. Inspired by both the maximum overlap method and recent progress in excited state variational principles, our approach combines these ideas in order to track individual excited states throughout the orbital optimization process. In a series of tests involving root flipping, near-degeneracies, charge transfers, and double excitations, we show that this approach is more effective for state-specific optimization than either the naive selection of roots based on energy ordering or a more direct generalization of the maximum overlap method. Furthermore, we provide evidence that this state-specific approach improves the performance of complete active space perturbation theory. With a simple implementation, a low cost, and compatibility with large active space methods, the approach is designed to be useful in a wide range of excited state investigations.Comment: 13 pages, submitted to JCT

Comorbidities only account for a small proportion of excess mortality after fracture: A record linkage study of individual fracture types

Background: Non-hip non-vertebral fractures (NHNV) constitute the majority of osteoporotic fractures but few studies have examined the association between these fractures, co-morbidity and mortality. Objective: To examine the relationship between individual non-hip non-vertebral fractures, co-morbidities and mortality. Methods: Prospective population-based cohort of 267,043 subjects (45 and Up Study, Australia) had baseline questionnaires linked to hospital administrative and all-cause mortality data from 2006 - 2013. Associations between fracture and mortality examined using multivariate, time dependent Cox models, adjusted for age, prior fracture, body mass index, smoking and co-morbidities (cardiovascular disease, diabetes, stroke, thrombosis and cancer) and survival function curves. Population attributable fraction calculated for each level of risk exposure. Results: During 1,490,651 person-years, women and men experienced 7,571 and 4,571 fractures and 7,064 deaths and 11,078 deaths, respectively. In addition to hip and vertebral fractures, pelvis, humerus, clavicle, rib, proximal tibia/fibula, elbow and distal forearm fractures in both sexes, and ankle fractures in men, were associated with increased multivariable adjusted mortality hazard ratios ranging from 1.3 to 3.4. Co-morbidity independently added to mortality such that a woman with a humeral fracture and one co-morbidity had a similarly reduced 5 year survival to that of a woman with a hip fracture and no co-morbidities. Population mortality attributable to any fracture without co-morbidity was 9.2% in women and 5.3% in men. Conclusion: All proximal non-hip, non-vertebral fractures in women and men were associated with increased mortality risk. Co-existent co-morbidities independently further increased mortality. Population attributable risk for mortality for fracture was similar to cardiovascular disease and diabetes, highlighting their importance and potential benefit for early intervention and treatment

Multiple days of heat exposure on firefighters\u27 work performance and physiology

This study assessed the accumulated effect of ambient heat on the performance of, and physiological and perceptual responses to, intermittent, simulated wildfire fighting tasks over three consecutive days. Firefighters (n = 36) were matched and allocated to either the CON (19°C) or HOT (33°C) condition. They performed three days of intermittent, self-paced simulated firefighting work, interspersed with physiological testing. Task repetitions were counted (and converted to distance or area) to determine work performance. Participants were asked to rate their perceived exertion and thermal sensation after each task. Heart rate, core temperature (Tc), and skin temperature (Tsk) were recorded continuously throughout the simulation. Fluids were consumed ad libitum. Urine volume was measured throughout, and urine specific gravity (USG) analysed, to estimate hydration. All food and fluid consumption was recorded. There was no difference in work output between experimental conditions. However, significant variation in performance responses between individuals was observed. All measures of thermal stress were elevated in the HOT, with core and skin temperature reaching, on average, 0.24 ± 0.08°C and 2.81 ± 0.20°C higher than the CON group. Participants\u27 doubled their fluid intake in the HOT condition, and this was reflected in the USG scores, where the HOT participants reported significantly lower values. Heart rate was comparable between conditions at nearly all time points, however the peak heart rate reached each circuit was 7 ± 3% higher in the CON trial. Likewise, RPE was slightly elevated in the CON trial for the majority of tasks. Participants\u27 work output was comparable between the CON and HOT conditions, however the performance change over time varied significantly between individuals. It is likely that the increased fluid replacement in the heat, in concert with frequent rest breaks and task rotation, assisted with the regulation of physiological responses (e.g., heart rate, core temperature)

Reduced mortality and subsequent fracture risk associated with oral bisphosphonate recommendation in a fracture liaison service setting: A prospective cohort study

Objective: Osteoporotic fragility fractures, that are common in men and women, signal increased risk of future fractures and of premature mortality. Less than one-third of postmenopausal women and fewer men are prescribed active treatments to reduce fracture risk. Therefore, in this study the association of oral bisphosphonate recommendation with subsequent fracture and mortality over eight years in a fracture liaison service setting was analysed. Materials and methods: In this prospective cohort study, 5011 men and women aged \u3e50 years, who sustained a clinical fracture, accepted the invitation to attend the fracture liaison service of the West Glasgow health service between 1999 and 2007. These patients were fully assessed and all were recommended calcium and vitamin D. Based on pre-defined fracture risk criteria, 2534 (50.7%) patients were additionally also recommended oral bisphosphonates. Mortality and subsequent fracture risk were the pre-defined outcomes analysed using Cox proportional hazard models. Results: Those recommended bisphosphonates were more often female (82.9 vs. 72.4%), were older (73.4 vs. 64.4 years), had lower bone mineral density T-score (-3.1 vs. -1.5) and more had sustained hip fractures (21.7 vs. 6.2%; p \u3c 0.001). After adjustments, patients recommended bisphosphonates had lower subsequent fracture risk (Hazard Ratio (HR): 0.60; 95% confidence interval (CI): 0.49±0.73) and lower mortality risk (HR: 0.79, 95%CI: 0.64±0.97). Conclusion: Of the patients, who are fully assessed after a fracture at the fracture liaison service, those with higher fracture risk and a recommendation for bisphosphonates had worse baseline characteristics. However, after adjusting for these differences, those recommended bisphosphonate treatment had a substantially lower risk for subsequent fragility fracture and lower risk for mortality. These community-based data indicate the adverse public health outcomes and mortality impacts of the current low treatment levels post fracture could be improved by bisphosphonate recommendation for both subsequent fracture and mortality

Establishment of novel neuroendocrine carcinoma patient-derived xenograft models for receptor peptide-targeted therapy

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of six mice developed tumors (NEC913 and NEC1452). Over 80% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2), whereas NEC1452 PDX tumors did not express SSTR2. Exome sequencing revealed loss o

Enhancing evidence informed policymaking in complex health systems: lessons from multi-site collaborative approaches

CITATION: Langlois, E. V., et al. 2016. Enhancing evidence informed policymaking in complex health systems: lessons from multi-site collaborative approaches. Health Research Policy and Systems, 14:20, doi:10.1186/s12961-016-0089-0.The original publication is available at http://health-policy-systems.biomedcentral.comENGLISH SUMMARY : Background: There is an increasing interest worldwide to ensure evidence-informed health policymaking as a means to improve health systems performance. There is a need to engage policymakers in collaborative approaches to generate and use knowledge in real world settings. To address this gap, we implemented two interventions based on iterative exchanges between researchers and policymakers/implementers. This article aims to reflect on the implementation and impact of these multi-site evidence-to-policy approaches implemented in low-resource settings. Methods: The first approach was implemented in Mexico and Nicaragua and focused on implementation research facilitated by communities of practice (CoP) among maternal health stakeholders. We conducted a process evaluation of the CoPs and assessed the professionals’ abilities to acquire, analyse, adapt and apply research. The second approach, called the Policy BUilding Demand for evidence in Decision making through Interaction and Enhancing Skills (Policy BUDDIES), was implemented in South Africa and Cameroon. The intervention put forth a ‘buddying’ process to enhance demand and use of systematic reviews by sub-national policymakers. The Policy BUDDIES initiative was assessed using a mixed-methods realist evaluation design. Results: In Mexico, the implementation research supported by CoPs triggered monitoring by local health organizations of the quality of maternal healthcare programs. Health programme personnel involved in CoPs in Mexico and Nicaragua reported improved capacities to identify and use evidence in solving implementation problems. In South Africa, Policy BUDDIES informed a policy framework for medication adherence for chronic diseases, including both HIV and non-communicable diseases. Policymakers engaged in the buddying process reported an enhanced recognition of the value of research, and greater demand for policy-relevant knowledge. Conclusions: The collaborative evidence-to-policy approaches underline the importance of iterations and continuity in the engagement of researchers and policymakers/programme managers, in order to account for swift evolutions in health policy planning and implementation. In developing and supporting evidence-to-policy interventions, due consideration should be given to fit-for-purpose approaches, as different needs in policymaking cycles require adapted processes and knowledge. Greater consideration should be provided to approaches embedding the use of research in real-world policymaking, better suited to the complex adaptive nature of health systems.http://health-policy-systems.biomedcentral.com/articles/10.1186/s12961-016-0089-0Publisher's versio

Nonstandard lumbar region in predicting fracture risk

Background: Femoral neck BMD is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1-L2 BMD compared to standard L2-L4 BMD and assess whether the addition of either lumbar spine site could improve fracture prediction over FN BMD. Methodology: A prospective cohort of 3016 women and men 60+ years from the Dubbo Osteoporosis Epidemiology Study followed for occurrence of minimal trauma fractures from 1989 to 2014. DXA was used to measure bone mineral density at f L1-L2, L2-L4 and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using ROC curve analyses Results:There were 565 women and 179 men with a minimal trauma fracture during a mean of 11±7 years. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p Conclusion: In an elderly population, L1-L2 is as good as but not better than L2-L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed

Case Study in Chamorro Community and Academic Engagement for a Community-Partnered Research Approach

Objective: We describe the development of a community and academic research partnership, share reflections on processes for collaborations, and identify key factors for establishing strong and effective relationships to foster high-quality research. Background: A community-based participatory research (CBPR) effort evaluating a community-based patient navigation program assisting Chamorro women to access breast cancer services in Southern California served as the foundation for the development of the community-academic partnership. Methods: Using a CBPR approach focusing on active involvement of community members, organizational representatives, and academic researchers in all aspects of research process, faculty from a research university and a local community-based organization were brought together to build a partnership. Community and academic partners engaged in a series of meetings where dialogue focused on developing and nurturing trust and shared values, respect for community knowledge, and establishing community-defined and prioritized needs and goals. Partners have also focused on defining and developing explicit structures and policies to implement an equal partnership. Results: Experiences and lessons learned are shared, reflecting the processes of relationship building, and planning and implementing preliminary research steps. Lessons Learned: Adequate time for relationship-building, open and honest communication, flexibility, and ongoing examination of assumptions are keys to developing successful CBPR partnerships

LGBTQ+ microaggressions in clinical skills training.

BACKGROUND Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) people experience health disparities. Implicit bias and mistreatment by healthcare providers can also lead LGTBQ+ people to delay care or avoid it entirely. Clinical skills training in the care of LGBTQ+ patients is therefore critical to health equity. Standardized patient (SP) encounters allow medical students to be assessed as providers in a mock clinical setting. METHODS The study population was rising third-year medical students at the University of Louisville School of Medicine in 2022. Out of 149 total encounters, coders reviewed all encounters with gender diverse SPs (n=86) and coded microaggressions, which are brief exchanges that send denigrating messages to certain individuals. Each video was reviewed by 3 coders. RESULTS LGBTQ+ microaggressions occurred in the majority (66%) of encounters between medical students and SPs. However, student use of homophobic or transphobic language was rare (3% of encounters). Generally, students appeared neutral or positive when speaking about hormone use and gender transition. Transgender and gender diverse SPs identified moments of discomfort and/or ways that students could improve in the care of trans and gender diverse patients in debriefs. Many SPs reported discomfort with the students\u27 assumptions, whether or not they were accurate. DISCUSSION LGBTQ+ healthcare microaggressions are pervasive. Addressing microaggressions requires practice and accountability. Outcomes from this work can be synthesized as part of curriculum development and as recommendations for medical training. Because this project focused on encounters between students and standardized patients, it may be limited in generalizability to actual patients