Association of Regional Variation in Primary Care Physicians’ Colorectal Cancer Screening Recommendations with Individual Use of Colorectal Cancer Screening

Introduction: Studies show that the recommendations of a primary care physician for colorectal cancer screening may be one important influence on an individual's use of screening. However, another possible influence, the effect of regional differences in physicians' beliefs and recommendations on screening use, has not been assessed. Methods: We linked data from the National Health Interview Survey on the use of colorectal cancer screening by respondents aged 50 years or older, by hospital-referral region, with data from the Survey of Colorectal Cancer Screening Practices on the colorectal cancer screening recommendations of primary care physicians, by region. Our principal independent variables were the proportion of physicians in a region who recommended screening at age 50 and continuing screening at the recommended frequency. Results: On average, 53.3% of physicians in a region correctly recommended initiating colorectal cancer screening, and 64.8% advised screening at the recommended frequency. Of adults who lived in regions where less than 30% of physicians correctly recommended initiating screening, 47.3% had been screened, in contrast to 54.8% in areas where 70% or more of physicians made correct recommendations. Seventy-one percent of respondents living in regions where less than 30% of physicians advised screening at the recommended frequency were current on screening, in contrast to 79.9% of respondents living in regions where 70% or more of physicians made this recommendation. These differences were statistically significant after adjustment for individual characteristics. Conclusion: Strategies to improve colorectal cancer screening recommendations of primary care physicians may improve the use of screening for millions of Americans.Version of Recor

A Comparison of Correlation-Agnostic Techniques for Magnetic Navigation

Navigation using a Global Navigation Satellite System (GNSS) is common for autonomous vehicles (ground or air). Unfortunately, GNSS-based navigation solutions are often susceptible to jamming, interference, and a limited number of satellites. A proposed technique to aid in navigation when a GNSS-based system fails is magnetic navigation - navigation using the Earth\u27s magnetic anomaly field. This solution comes with its own set of problems including the need for quality magnetic maps in every area in which magnetic navigation will be used. Many of the currently available magnetic maps are generated from a combination of dated magnetic surveys, resulting in maps riddled with spatially correlated errors, the correlation structure of which is largely unknown. The correlations are further confounded while navigating because they depend on how fast a vehicle moves through the map in addition to the original correlated error structure. Traditionally, this spatial correlation has been handled by introducing a First Order Gauss-Markov (FOGM) noise model into the estimation routine, with the FOGM parameters set somewhat arbitrarily. In this paper, we investigate the possibility of using correlation agnostic fusion techniques (i.e., Covariance Intersection and Probabilistically Conservative Fusion) for magnetic navigation. These techniques have the advantage of not requiring any parameter tuning; the same method and tuning parameters are used regardless of the spatial correlation. We demonstrate that utilizing probabilistically conservative fusion leads to navigation results that are better than many tuned approaches and reasonably close to the best possible tuning parameters of a FOGM

Tissue Culture of Secondary Xylem Parenchyma of Four Species of Southern Pines

Callus was grown from increment core explants of longleaf pine (Pinus palustris Mill.), slash pine (P. elliottii Engelm.), loblolly pine (P. taeda L.), and shortleaf pine (P. echinata Mill.) trees that had 30-45 annual rings of sapwood. Callus emanated from vertical and horizontal resin canals and uniserate rays. It originated from epithelial cells and longitudinal and ray parenchyma cells. There was relatively little difference in the amount of callus produced from the outer to inner sapwood of longleaf and slash pines compared to the reduction that occurred in loblolly and shortleaf pines. Production was generally lower in the transition zone, especially in loblolly and shortleaf pines, and virtually nonexistent in the heartwood. Several current theories of heartwood formation are discussed in light of the results

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Biopolitics meets Terrapolitics: Political Ontologies and Governance in Settler-Colonial Australia

Crises persist in Australian Indigenous affairs because current policy approaches do not address the intersection of Indigenous and European political worlds. This paper responds to this challenge by providing a heuristic device for delineating Settler and Indigenous Australian political ontologies and considering their interaction. It first evokes Settler and Aboriginal ontologies as respectively biopolitical (focused through life) and terrapolitical (focused through land). These ideal types help to identify important differences that inform current governance challenges. The paper discusses the entwinement of these traditions as a story of biopolitical dominance wherein Aboriginal people are governed as an “included-exclusion” within the Australian political community. Despite the overall pattern of dominance, this same entwinement offers possibilities for exchange between biopolitics and terrapolitics, and hence for breaking the recurrent crises of Indigenous affairs

Relationship between low Ankle-Brachial Index and rapid renal function decline in patients with atrial fibrillation: A prospective multicentre cohort study

OBJECTIVE: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). DESIGN: Observational prospective multicentre cohort study. SETTING:Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. PARTICIPANTS: 897 AF patients on treatment with vitamin K antagonists. MAIN OUTCOME MEASURES: The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. RESULTS: Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). CONCLUSIONS: In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration

Non-invasive management of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is common and symptoms can be debilitating and lethal. Risk management, exercise, radiological and surgical intervention are all valuable therapies, but morbidity and mortality rates from this disease are increasing. Circulatory enhancement can be achieved using simple medical electronic devices, with claims of minimal adverse side effects. The evidence for these is variable, prompting a review of the available literature. METHODS: Embase and Medline were interrogated for full text articles in humans and written in English. Any external medical devices used in the management of peripheral arterial disease were included if they had objective outcome data. RESULTS: Thirty-one papers met inclusion criteria, but protocols were heterogenous. The medical devices reported were intermittent pneumatic compression (IPC), electronic nerve (NMES) or muscle stimulators (EMS), and galvanic electrical dressings. In patients with intermittent claudication, IPC devices increase popliteal artery velocity (49-70 %) and flow (49-84 %). Gastrocnemius EMS increased superficial femoral artery flow by 140 %. Over 4.5-6 months IPC increased intermittent claudication distance (ICD) (97-150 %) and absolute walking distance (AWD) (84-112 %), with an associated increase in quality of life. NMES of the calf increased ICD and AWD by 82 % and 61-150 % at 4 weeks, and 26 % and 34 % at 8 weeks. In patients with critical limb ischaemia IPC reduced rest pain in 40-100 % and was associated with ulcer healing rates of 26 %. IPC had an early limb salvage rate of 58-83 % at 1-3 months, and 58-94 % at 1.5-3.5 years. No studies have reported the use of EMS or NMES in the management of CLI. CONCLUSION: There is evidence to support the use of IPC in the management of claudication and CLI. There is a building body of literature to support the use of electrical stimulators in PAD, but this is low level to date. Devices may be of special benefit to those with limited exercise capacity, and in non-reconstructable critical limb ischaemia. Galvanic stimulation is not recommended

Expert consensus document: A 'diamond' approach to personalized treatment of angina.

In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for traditional first-choice drugs. Considering some drugs, but not others, to be first choice is, therefore, difficult. Moreover, double or triple therapy is often needed to control angina. Patients with angina can have several comorbidities, and symptoms can result from various underlying pathophysiologies. Some agents, in addition to having antianginal effects, have properties that could be useful depending on the comorbidities present and the mechanisms of angina, but the guidelines do not provide recommendations on the optimal combinations of drugs. In this Consensus Statement, we propose an individualized approach to angina treatment, which takes into consideration the patient, their comorbidities, and the underlying mechanism of disease