Floquet Engineering Topological Many-Body Localized Systems.

We show how second-order Floquet engineering can be employed to realize systems in which many-body localization coexists with topological properties in a driven system. This allows one to implement and dynamically control a symmetry protected topologically ordered qubit even at high energies, overcoming the roadblock that the respective states cannot be prepared as ground states of nearest-neighbor Hamiltonians. Floquet engineering-the idea that a periodically driven nonequilibrium system can effectively emulate the physics of a different Hamiltonian-is exploited to approximate an effective three-body interaction among spins in one dimension, using time-dependent two-body interactions only. In the effective system, emulated topology and disorder coexist, which provides an intriguing insight into the interplay of many-body localization that defies our standard understanding of thermodynamics and into the topological phases of matter, which are of fundamental and technological importance. We demonstrate explicitly how combining Floquet engineering, topology, and many-body localization allows one to harvest the advantages (time-dependent control, topological protection, and reduction of heating, respectively) of each of these subfields while protecting them from their disadvantages (heating, static control parameters, and strong disorder).

Changes in primary care provider utilization by phase of care for women diagnosed with breast cancer: a CanIMPACT longitudinal cohort study.

BACKGROUND: Primary care providers (PCPs) have always played an important role in cancer diagnosis. There is increasing awareness of the importance of their role during treatment and survivorship. We examined changes in PCP utilization from pre-diagnosis to survival for women diagnosed with breast cancer, factors associated with being a high user of primary care, and variation across four Canadian provinces. METHODS: The cohorts included women 18+ years of age diagnosed with stage I-III invasive breast cancer in years 2007-2012 in British Columbia (BC), Manitoba (MB), Ontario (ON), and Nova Scotia (NS) who had surgery plus adjuvant chemotherapy and were alive 30+ months after diagnosis (N = 19,589). We compared the rate of PCP visits in each province across phases of care (pre-diagnosis, diagnosis, treatment, and survival years 1 to 4). RESULTS: PCP use was greatest during treatment and decreased with each successive survival year in all provinces. The unadjusted difference in PCP use between treatment and pre-diagnosis was most pronounced in BC where PCP use was six times higher during treatment than pre-diagnosis. Factors associated with being a high user of primary care during treatment included comorbidity and being a high user of care pre-diagnosis in all provinces. These factors were also associated with being a higher user of care during diagnosis and survival. CONCLUSIONS: Contrary to the traditional view that PCPs focus primarily on cancer prevention and early detection, we found that PCPs are involved in the care of women diagnosed with breast cancer across all phases of care.

Cross-Canada differences in early-stage breast cancer treatment and acute-care use.

Background: Chemotherapy has improved outcomes in early-stage breast cancer, but treatment practices vary, and use of acute care is common. We conducted a pan-Canadian study to describe treatment differences and the incidence of emergency department visits (edvs), edvs leading to hospitalization (edvhs), and direct hospitalizations (hs) during adjuvant chemotherapy. Methods: The cohort consisted of women diagnosed with early-stage breast cancer (stages i-iii) during 2007-2012 in British Columbia, Manitoba, Ontario, or Nova Scotia who underwent curative surgery. Parallel provincial analyses were undertaken using linked clinical, registry, and administrative databases. The incidences of edvs, edvhs, and hs in the 6 months after treatment initiation were examined for patients treated with adjuvant chemotherapy. Results: The cohort consisted of 50,224 patients. The proportion of patients who received chemotherapy varied by province, with Ontario having the highest proportion (46.4%), and Nova Scotia, the lowest proportion (38.0%). Age, stage, receptor status, comorbidities, and geographic location were associated with receipt of chemotherapy in all provinces. Ontario had the highest proportion of patients experiencing an edv (36.1%), but the lowest proportion experiencing h (6.4%). Conversely, British Columbia had the lowest proportion of patients experiencing an edv (16.0%), but the highest proportion experiencing h (26.7%). The proportion of patients having an edvh was similar across provinces (13.9%-16.8%). Geographic location was associated with edvs, edvhs, and hs in all provinces. Conclusions: Intra- and inter-provincial differences in the use of chemotherapy and acute care were observed. Understanding variations in care can help to identify gaps and opportunities for improvement and shared learnings.

Assessing the impact of mailing self-sampling kits for human papillomavirus testing to unscreened non-responder women in Manitoba.

Background: CervixCheck, Manitoba's cervical cancer screening program, conducted a pilot study to assess whether screening participation could be improved in unscreened women by offering a mailed self-sampling kit for human papillomavirus (hpv) testing instead of a Pap test. Methods: In a prospective cohort study design, a sample of unscreened women (n = 1052) who had been sent an invitation letter from CervixCheck in the past but who did not respond were randomized to either an intervention group or a control group. The intervention group received a mailed hpv self-sampling kit; the control group received no additional communication. Returned hpv self-sampling swabs were analyzed by a provincial laboratory. After 6 months, screening participation in the two study groups was compared using a logistic regression model adjusted for age and area of residence (urban or rural). Secondary outcomes included hpv positivity, specimen inadequacy, compliance with follow-up, and time to colposcopy. Results: Screening participation was significantly higher in the intervention group than in the control group (n = 51, 9.6%, vs. n = 13, 2.5%; odds ratio: 4.7; 95% confidence interval: 2.56 to 8.77). Geographic area of residence (urban or rural) and age were not statistically significant. Conclusions: The study demonstrated that hpv self-sampling kits can enhance screening participation in unscreened non-responder women in the setting of an organized screening program. Next steps should include additional research to determine the best implementation strategy for hpv self-sampling in Manitoba.

Measuring colposcopy quality in Canada: development of population-based indicators.

Background: Colposcopy is a key part of cervical cancer control. As cervical cancer screening and prevention strategies evolve, monitoring colposcopy performance will become even more critical. In the present paper, we describe population-based colposcopy quality indicators that are recommended for ongoing measurement by cervical cancer screening programs in Canada. Methods: The Pan-Canadian Cervical Cancer Screening Network established a multidisciplinary expert working group to identify population-based colposcopy quality indicators. A systematic literature review was conducted to ascertain existing population and program-level colposcopy quality indicators. A systems-level cervical cancer screening pathway describing each step from an abnormal screening test, to colposcopy, and back to screening was developed. Indicators from the literature were assigned a place on the pathway to ensure that all steps were measured. A prioritization matrix scoring system was used to score each indicator based on predetermined criteria. Proposed colposcopy quality indicators were shared with provincial and territorial screening programs and subsequently revised. Results: The 10 population-based colposcopy quality indicators identified as priorities were colposcopy uptake, histologic investigation (biopsy) rate, colposcopy referral rate, failure to attend colposcopy, treatment frequency in women 18-24 years of age, re-treatment proportion, colposcopy exit-test proportion, histologic investigation (biopsy) frequency after low-grade Pap test results, length of colposcopy episode of care, and operating room treatment rate. Two descriptive indicators were also identified: colposcopist volume and number of colposcopists per capita. Summary: High-quality colposcopy services are an essential component of provincial cervical cancer screening programs. The proposed quality and descriptive indicators will permit colposcopy outcomes to be compared between provinces and across Canada so as to identify opportunities for improving colposcopy services.

Use of physician services during the survivorship phase: a multi-province study of women diagnosed with breast cancer.

INTRODUCTION: Oncologists have traditionally been responsible for providing routine follow-up care for cancer survivors; in recent years, however, primary care providers (pcps) are taking a greater role in care during the follow-up period. In the present study, we used a longitudinal multi-province retrospective cohort study to examine how primary care and specialist care intersect in the delivery of breast cancer follow-up care. METHODS: Various databases (registry, clinical, and administrative) were linked in each of four provinces: British Columbia, Manitoba, Ontario, and Nova Scotia. Population-based cohorts of breast cancer survivors were identified in each province. Physician visits were identified using billings or claims data and were classified as visits to primary care (total, breast cancer-specific, and other), oncology (medical oncology, radiation oncology, and surgery), and other specialties. The mean numbers of visits by physician type and specialty, or by combinations thereof, were examined. The mean numbers of visits for each follow-up year were also examined by physician type. RESULTS: The results showed that many women (>64%) in each province received care from both primary care and oncology providers during the follow-up period. The mean number of breast cancer-specific visits to primary care and visits to oncology declined with each follow-up year. Interprovincial variations were observed, with greater surgeon follow-up in Nova Scotia and greater primary care follow-up in British Columbia. Provincial differences could reflect variations in policies and recommendations, relevant initiatives, and resources or infrastructure to support pcp-led follow-up care. CONCLUSIONS: Optimizing the role of pcps in breast cancer follow-up care might require strategies to change attitudes about pcp-led follow-up and to better support pcps in providing survivorship care.

Multigene expression profile testing in breast cancer: is there a role for family physicians?

BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.

Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.

Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit ER signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the upregulation of alternative growth signals. The mechanisms that drive this resistance-especially epigenetic events that alter gene expression-are, however, not well understood. Genome-wide DNA methylation and expression analysis of cell line models of acquired AI resistance indicated that prostaglandin E2 receptor 4 (PTGER4) is upregulated after demethylation in resistant cells. Knockdown and inhibitor studies demonstrate that PTGER4 is essential for estrogen-independent growth. Our exploratory analysis of downstream signaling indicates that PTGER4 likely promotes AI resistance via ligand-independent activation of the ERα-cofactor CARM1. We believe that we have discovered a novel epigenetic mechanism for altering cell signaling and acquiring endocrine therapy resistance. Our findings indicate that PTGER4 is a potential drug target in AI-resistant cancers. In addition, the epigenetic component of PTGER4 regulation suggests that further study of PTGER4 may yield valuable insights into how DNA methylation-targeted diagnoses and treatments can improve AI-resistant breast cancer treatment.

Cancer incidence, mortality, and stage at diagnosis in First Nations living in Manitoba.

BACKGROUND: In the present study, we examined breast (bca) and colorectal cancer (crc) incidence and mortality and stage at diagnosis for First Nations (fn) individuals and all other Manitobans (aoms). METHODS: Several population-based databases were linked to determine ethnicity and to calculate age-standardized incidence and mortality rates. Logistic regression was used to compare bca and crc stage at diagnosis. RESULTS: From 1984-1988 to 2004-2008, the incidence of bca increased for fn and aom women. Breast cancer mortality increased for fn women and decreased for aom women. First Nations women were significantly more likely than aom women to be diagnosed at stages iii-iv than at stage i [odds ratio (or) for women ≤50 years of age: 3.11; 95% confidence limits (cl): 1.20, 8.06; or for women 50-69 years of age: 1.72; 95% cl: 1.03, 2.88). The incidence and mortality of crc increased for fn individuals, but decreased for aoms. First Nations status was not significantly associated with crc stage at diagnosis (or for stages i-ii compared with stages iii-iv: 0.98; 95% cl: 0.68, 1.41; or for stages i-iii compared with stage iv: 0.91; 95% cl: 0.59, 1.40). CONCLUSIONS: Our results underscore the need for improved cancer screening participation and targeted initiatives that emphasis collaboration with fn communities to reduce barriers to screening and to promote healthy lifestyles.

Recent trends in breast, cervical, and colorectal cancer screening test utilization in Canada, using self-reported data from 2008 and 2012.

In Canada, self-reported data from the Canadian Community Health Survey 2008 and 2012 provide an opportunity to examine overall utilization of breast, cervical, and colorectal cancer screening tests for both programmatic and opportunistic screening. Among women 50-74 years of age, utilization of screening mammography was stable (62.0% in 2008 and 63.0% in 2012). Pap test utilization for women 25-69 years of age remained high and stable across Canada in 2008 and 2012 (78.9% in 2012). The percentage of individuals 50-74 years of age who reporting having at least 1 fecal test within the preceding 2 years increased in 2012 (to 23.0% from 16.9% in 2008), but remains low. Stable rates of screening mammography utilization (about 30%) were reported in 2008 and 2012 among women 40-49 years of age, a group for which population-based screening is not recommended. Although declining over time, cervical cancer screening rates were high for women less than 25 years of age (for whom screening is not recommended). Interestingly, an increased percentage of women 70-74 years of age reported having a Pap test. In 2012, a smaller percentage of women 50-69 years of age reported having no screening test (5.9% vs. 8.5% in 2008), and more women reported having the three types of cancer screening tests (19.0% vs. 13.2%). Efforts to encourage use of screening within the recommended average-risk age groups are needed, and education for stakeholders about the possible harms of screening outside those age groups has to continue.

Demographic trends of sick leave absenteeism among civil service employees at a federal agency from 2004 to 2012.

OBJECTIVE: To investigate the associations between demographic variables and sick leave use. METHODS: We analyzed sick leave use among civil servants at a federal agency (FA) from 2004 to 2012 by demographic and FA-specific variables. We used a mixed methods approach and type III analysis to build a descriptive model of sick leave proportions and demographic variables. RESULTS: Sick absenteeism usage varied significantly (variation of greater than one sick day per year) by sex, Emergency Operations Center response tier, length of service at the FA, age, and general schedule pay grade level. Our final descriptive model contained age, sex, response tier and an interaction term between age and sex. CONCLUSIONS: Future studies should examine these associations on smaller time scales, perhaps breaking the data down by month or day of the week.

Predicting temporal trends in total absenteeism rates for civil service employees of a federal public health agency.

OBJECTIVE: This study evaluates the predictability in temporal absences trends due to all causes (total absenteeism) among employees at a federal agency. The objective is to determine how leave trends vary within the year, and determine whether trends are predictable. METHODS: Ten years of absenteeism data from an attendance system were analyzed for rates of total absence. RESULTS: Trends over a 10-year period followed predictable and regular patterns during a given year that correspond to major holiday periods. Temporal trends in leave among small, medium, and large facilities compared favorably with the agency as a whole. CONCLUSIONS: Temporal trends in total absenteeism rates for an organization can be determined using its attendance system. The ability to predict employee absenteeism rates can be extremely helpful for management in optimizing business performance and ensuring that an organization meets its mission.

An in vivo RNAi screen identifies SALL1 as a tumor suppressor in human breast cancer with a role in CDH1 regulation.

The gold standard for determining the tumorigenic potential of human cancer cells is a xenotransplantation into immunodeficient mice. Higher tumorigenicity of cells is associated with earlier tumor onset. Here, we used xenotransplantation to assess the tumorigenic potential of human breast cancer cells following RNA interference-mediated inhibition of over 5000 genes. We identify 16 candidate tumor suppressors, one of which is the zinc-finger transcription factor SALL1. Analyzing this particular molecule in more detail, we show that inhibition of SALL1 correlates with reduced levels of CDH1, an important contributor to epithelial-to-mesenchymal transition. Furthermore, SALL1 expression led to an increased migration and more than twice as many cells expressing a cancer stem cell signature. Also, SALL1 expression correlates with the survival of breast cancer patients. These findings cast new light on a gene that has previously been described to be relevant during embryogenesis, but not carcinogenesis.

Effects of four treatment strategies for temporomandibular joint closed lock.

A previous randomized controlled trial (RCT) by Schiffman et al. (2007)(15) compared four treatments strategies for temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock). In this parallel group RCT, 106 patients with magnetic resonance imaging (MRI)-confirmed TMJ closed lock were randomized between medical management, non-surgical rehabilitation, arthroscopic surgery, and arthroplasty. Surgical groups also received rehabilitation post-surgically. The current paper reassesses the effectiveness of these four treatment strategies using outcome measures recommended by the International Association of Oral and Maxillofacial Surgeons (IAOMS). Clinical assessments at baseline and at follow-up (3, 6, 12, 18, 24, and 60 months) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing. TMJ MRIs were performed at baseline and 24 months, and TMJ tomograms at baseline, 24 and 60 months. Most IAOMS recommended outcome measures improved significantly over time (P≤0.0003). There was no difference between treatment strategies relative to any treatment outcome at any follow-up (P≥0.16). Patient self-assessment of treatment success correlated with their ability to eat, with pain-free opening ≥35mm, and with reduced pain intensity. Given no difference between treatment strategies, non-surgical treatment should be employed for TMJ closed lock before considering surgery.

Changes in cervical cancer screening behavior for women attending Pap Test Week clinics.

OBJECTIVE: This retrospective study of all women who accessed the 2006 Manitoba Pap Test Week clinics was designed to determine factors associated with inadequate cervical cancer screening and changes in cervical cancer screening behavior. METHODS: Data were acquired using the CervixCheck Manitoba registry and an ancillary database of demographic information collected from clinic attendees. RESULTS: The study included 1124 women. Of these, 53% (n = 598) were under-screened (no Pap test in the previous 2 years) prior to accessing the clinics. Logistic regression analyses demonstrated that older age (odds ratio [OR] = 1.02, 95% confidence interval [CI] 1.01-1.03), no doctor (OR = 1.4, 95% CI 1.05-1.54), and living in Canada < 1 year (OR = 5.5, 95% CI 2.73-11.12) were associated with being under-screened prior to accessing the Pap Test Week clinics. Thirty-seven percent (n = 223) of under-screened women demonstrated improved screening status subsequent to the 2006 Pap Test Week (had a subsequent Papanicolaou [Pap] test performed within 2 years) and these women were more likely to live in an urban setting (P = 0.003), be younger (P < 0.001), originate outside Canada (P = 0.006), have lived in Canada for less than 1 year (P = 0.006), and have had an abnormal Pap test result in 2006 (P < 0.001). Previously under-screened women were less likely to become adequately-screened subsequent to 2006 if they had a Pap test performed at a Pap Test Week clinic compared to having a Pap test performed elsewhere (37% versus 60%, P < 0.001). CONCLUSION: This study identified a subset of under-screened women accessing Pap Test Week clinics whose screening status might be most modifiable.

Predicting temporal trends in sickness absence rates for civil service employees of a federal public health agency.

OBJECTIVE: To determine whether trends of sickness in employees at a federal agency are predictable, and whether the variance was minimal enough to detect unusual levels of employee illness for further investigation. METHODS: Ten years of absenteeism data from an attendance system were analyzed for rates of sickness absence. Specifically, week of year and day of week were used to describe temporal trends. RESULTS: This study evaluates the predictability in temporal absence trends due to sickness among employees at a federal agency. Trends follow regular patterns during a given year that correspond to seasonal illnesses. Temporal trends in sick leave have been proven to be very predictable. CONCLUSION: The minimal variance allows the detection of sick leave anomalies that may be ascribable to specific causes, allowing the business or agency to follow-up and develop interventions.

Electrical neuromodulation for patients with cardiac diseases.

In this review we discuss the position of electrical neuromodulation as a safe and reversible adjuvant therapy for treatment of patients with chronic cardiac diseases who have become refractory to conventional strategies. In patients with chronic refractory angina, electrical neuromodulation, independent of the applied modality, has shown to reduce complaints of angina, to enhance exercise capacity, to improve quality of life and to employ anti-ischaemic effects. To date, electrical neuromodulation seems to be one of the best adjuvant therapies for these patients. In addition, neuromodulation in the treatment of heart failure and resistant arrhythmias is the subject of several ongoing studies.