Course Notes: United States Particle Accelerator School Beam Physics with Intense Space-Charge

The purpose of this course is to provide a comprehensive introduction to the physics of beams with intense space charge. This course is suitable for graduate students and researchers interested in accelerator systems that require sufficient high intensity where mutual particle interactions in the beam can no longer be neglected. This course is intended to give the student a broad overview of the dynamics of beams with strong space charge. The emphasis is on theoretical and analytical methods of describing the acceleration and transport of beams. Some aspects of numerical and experimental methods will also be covered. Students will become familiar with standard methods employed to understand the transverse and longitudinal evolution of beams with strong space charge. The material covered will provide a foundation to design practical architectures. In this course, we will introduce you to the physics of intense charged particle beams, focusing on the role of space charge. The topics include: particle equations of motion, the paraxial ray equation, and the Vlasov equation; 4-D and 2-D equilibrium distribution functions (such as the Kapchinskij-Vladimirskij, thermal equilibrium, and Neuffer distributions), reduced moment and envelope equation formulations of beam evolution; transport limits and focusing methods; the concept of emittance and the calculation of its growth from mismatches in beam envelope and from space-charge non-uniformities using system conservation constraints; the role of space-charge in producing beam halos; longitudinal space-charge effects including small amplitude and rarefaction waves; stable and unstable oscillation modes of beams (including envelope and kinetic modes); the role of space charge in the injector; and algorithms to calculate space-charge effects in particle codes. Examples of intense beams will be given primarily from the ion and proton accelerator communities with applications from, for example, heavy-ion fusion, spallation neutron sources, nuclear waste transmutation, etc

Quick and simple: psoas density measurement is an independent predictor of anastomotic leak and other complications after colorectal resection

Purpose: Radiologically-defined sarcopenia has been shown to predict negative outcomes after cancer surgery, however radiological assessment of sarcopenia often requires additional software and standardisation against anthropomorphic data. Measuring psoas density using hospital Picture Archiving and Communication Systems, universally available in the UK, may have advantages over methods requiring the use of additional specialist and often costly software. This study aimed to assess the association between radiologically-defined sarcopenia measured by psoas density and postoperative outcome in patients having a colorectal cancer resectionMethods: All patients having a resection for colorectal cancer, discussed at the colorectal multi-disciplinary team in one institution between 1/1/15 and 31/12/15, were retrospectively identified. Mean psoas density at the level of the L3 vertebra were analysed from preoperative CT scans to define sarcopenia. Postoperative complications and mortality were recorded.Results: One hundred and sixty-nine patients had a colorectal resection for cancer and 140 of these had a primary anastomosis. Ninety-day mortality and 1-year mortality was 1.1% and 7.1% respectively. Eighteen(10.7%) patients suffered a Clavien-Dindo(CD) grade 3 or 4 complication of which 6(33%) were anastomotic leaks. In the whole cohort, sarcopenia was associated with an increased risk of CD3/4 complication(adjusted OR 6.33(1.65-24.23) p= 0.007). In those who had an anastomosis, sarcopenia was associated with an increased risk of anastomotic leak (adjusted OR 14.37(1.37-150.04) p=0.026).Conclusions: A quick and easy radiological assessment of sarcopenia using psoas density on standard hospital PACS is associated with a 6-fold increased risk of major post-operative complication and a 14-fold increase in anastomotic leak

The Origin of Galactic Cosmic Rays

Motivated by recent measurements of the major components of the cosmic radiation around 10 TeV/nucleon and above, we discuss the phenomenology of a model in which there are two distinct kinds of cosmic ray accelerators in the galaxy. Comparison of the spectra of hydrogen and helium up to 100 TeV per nucleon suggests that these two elements do not have the same spectrum of magnetic rigidity over this entire region and that these two dominant elements therefore receive contributions from different sources.Comment: To be published in Physical Review D, 13 pages, with 3 figures, uuencode

Association between beta-blocker use and mortality/morbidity in patients with heart failure with reduced, midrange, and preserved ejection fraction and advanced chronic kidney disease

Background:It is unknown if beta-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials.Methods:Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m(2)) from the Swedish Heart Failure Registry between 2001 and 2016. We first explored associations between beta-blocker use, 5-year death, and the composite of cardiovascular death/HF hospitalization among 3775 patients with HF with reduced ejection fraction (HFrEF) and advanced CKD. We compared observed hazards with those from a control cohort of 15 346 patients with HFrEF and moderate CKD (estimated glomerular filtration rate <60-30 mL/min per 1.73 m(2)), for whom beta-blocker trials demonstrate benefit. Second, we explored outcomes associated to beta-blocker among advanced CKD participants with preserved (HFpEF; N=2009) and midrange ejection fraction (HFmrEF; N=1514).Results:During a median follow-up of 1.3 years, 2012 patients had a subsequent HF hospitalization, and 2849 died in the HFrEF cohort, of which 2016 died due to cardiovascular causes. Among patients with HFrEF, beta-blocker use was associated with lower risk of death (adjusted hazard ratio 0.85 [95% CI, 0.75-0.96]) and cardiovascular mortality/HF hospitalization (0.87 [0.77-0.98]) compared with nonuse. The magnitude of the associations was similar to that observed for HFrEF patients with moderate CKD. Conversely, no significant association was observed for beta-blocker users in advanced CKD with HFpEF (death: 0.88 [0.77-1.02], cardiovascular mortality/HF hospitalization: 1.05 [0.90-1.23]) or HFmrEF (death: 0.95 [0.79-1.14], cardiovascular mortality/HF hospitalization: 1.09 [0.90-1.31]).Conclusions:In HFrEF patients with advanced CKD, the use of beta-blockers was associated with lower morbidity and mortality. Although inconclusive due to limited power, these benefits were not observed in similar patients with HFpEF or HFmrEF.Clinical epidemiolog

Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States

Background Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. Study Design Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. Results Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69–0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74–0.83). Conclusions Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment

Evaluating the effectiveness of neoadjuvant chemotherapy in reducing mastectomy for women with breast cancer

Background: Neoadjuvant chemotherapy in breast cancer reduced mastectomy rates by 7% to 13% in randomized trials. However, the differential effects for women with different stages, receptor subtypes, and ages are unknown. We compared mastectomy rates in women who did vs did not receive neoadjuvant chemotherapy in 18 patient subgroups. The main objective was to quantify the potential benefit from neoadjuvant chemotherapy in reducing mastectomy rates for each subgroup. Methods: Our retrospective analysis used data from the National Cancer Data Base, which includes approximately 70% of incident cancers across the United States. Absolute risk reductions for mastectomy were determined for 18 subgroups of clinical stage, receptor subtype, and age group. In each subgroup, propensity score weighting balanced measured covariates between women treated with vs without neoadjuvant chemotherapy. Results: A total of 55 709 patients were analyzed. In clinical stage IIA disease, only patients with human epidermal growth factor receptor 2 (HER2)-positive tumors had reduced mastectomy rates associated with neoadjuvant chemotherapy (age < 60 years, 12%; age ≥ 60 years, 12.6%). For stage IIB cancers, neoadjuvant chemotherapy was associated with an absolute reduction in mastectomy rates of 5.9% in women younger than age 60 years with hormone receptor-positive/HER2- disease, 8.2% to 10.7% for triple-negative disease, and 11.7% to 17.4% for HER2+ disease. For stage IIIA, the reductions in mastectomy rates ranged from 6.6% to 15.9%. Conclusions: In an analysis of patients treated across the United States, we found that neoadjuvant chemotherapy was associated with a reduction in mastectomy rates to a similar magnitude overall as shown in randomized trials, but this benefit varied widely by patient subgroup. This study provides novel information to help women make informed decisions regarding treatment

Exercise and other nonpharmacological strategies to reduce blood pressure in older adults: a systematic review and meta-analysis

The incidence of hypertension increases with advancing age and represents a significant burden of disease. Lifestyle modification represents the first-line intervention in treatment algorithms; however, the majority of evidence for this comes from studies involving young participants using interventions that may not always be feasible in the elderly. This manuscript presents a systematic review of all randomized controlled trials involving participants with a mean age of 65 or over investigating nonpharmacological strategies to reduce blood pressure (BP). Fifty-three randomized controlled trials were included. The majority of interventions described aerobic exercise training, dynamic resistance exercise training, or combined aerobic and dynamic resistance exercise training (COM), with limited studies reporting isometric exercise training or alternative lifestyle strategies. Aerobic exercise training, dynamic resistance exercise training, COM, and isometric exercise training all elicited significant reductions in both systolic and diastolic BP, with no additional benefit of COM compared with single modality exercise training. Three months of traditional exercise-based lifestyle intervention may produce a reduction in BP of approximately 5 mmHg systolic and 3 mmHg diastolic in older individuals, similar to that expected in younger individuals

Astrophysical Uncertainties in the Cosmic Ray Electron and Positron Spectrum From Annihilating Dark Matter

In recent years, a number of experiments have been conducted with the goal of studying cosmic rays at GeV to TeV energies. This is a particularly interesting regime from the perspective of indirect dark matter detection. To draw reliable conclusions regarding dark matter from cosmic ray measurements, however, it is important to first understand the propagation of cosmic rays through the magnetic and radiation fields of the Milky Way. In this paper, we constrain the characteristics of the cosmic ray propagation model through comparison with observational inputs, including recent data from the CREAM experiment, and use these constraints to estimate the corresponding uncertainties in the spectrum of cosmic ray electrons and positrons from dark matter particles annihilating in the halo of the Milky Way.Comment: 21 pages, 9 figure

Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star

A search of the time-series photometry from NASA's Kepler spacecraft reveals a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626 with a period of 290 days. The characteristics of the host star are well constrained by high-resolution spectroscopy combined with an asteroseismic analysis of the Kepler photometry, leading to an estimated mass and radius of 0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the planet. The system passes a battery of tests for false positives, including reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A full BLENDER analysis provides further validation of the planet interpretation by showing that contamination of the target by an eclipsing system would rarely mimic the observed shape of the transits. The final validation of the planet is provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year span. Although the velocities do not lead to a reliable orbit and mass determination, they are able to constrain the mass to a 3{\sigma} upper limit of 124 MEarth, safely in the regime of planetary masses, thus earning the designation Kepler-22b. The radiative equilibrium temperature is 262K for a planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is a rocky planet, it is the first confirmed planet with a measured radius to orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap

Real-World Evidence: What It Is and What It Can Tell Us According to the International Society for Pharmacoepidemiology (ISPE) Comparative Effectiveness Research (CER) Special Interest Group (SIG)

On December 8, 2016, the New England Journal of Medicine published a sounding board on Real World Evidence (RWE)1 by the US Food and Drug Administration (FDA) leadership. While the value of RWE based on nonrandomized observational studies was appreciated, such as for hypothesis generating, safety, and measuring quality in healthcare delivery, the authors expressed concerns on the quality of data sources and the ability of methodologies to control for confounding. In response, we offer a few considerations regarding these concerns