The relationship between repeated measurements of HbA1c and risk of coronary events among the common haptoglobin phenotype groups: the Action for Health in Diabetes (Look AHEAD) study.

BACKGROUND: In the ACCORD study, participants with the haptoglobin (Hp) 2-2 phenotype and glycated hemoglobin (HbA1c) ≥ 8.0% had a higher risk of coronary artery disease (CAD) compared to those with HbA1c 7.0-7.9%. However, this association was not observed in participants without the Hp2-2 phenotype. The optimal glycemic target for CAD prevention for the Hp phenotypes remains uncertain and may vary based on demographic and clinical factors. OBJECTIVE: To investigate how reaching clinically relevant HbA1c targets relates to the risk of CAD in different Hp phenotype groups among a diverse cohort of individuals with T2DM (the Look AHEAD study, HbA1c ≤ 11% at baseline). METHODS: Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (< 6.5%, 6.5-6.9%, and ≥ 8.0% compared to 7.0-7.9%), updated at years 1-4, 6, 8, and 10, and incident CAD in the Hp2-2 (n = 1,587) and non-Hp2-2 (n = 2,944) phenotypes separately. Further pre-specified subgroup analyses by age, sex, history of cardiovascular disease (CVD), race, and diabetes duration were performed in each Hp phenotype group separately. RESULTS: Compared with HbA1c 7.0-7.9%, having HbA1c < 6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 phenotype (adjusted HR 0.71, 95% CI 0.55-0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 phenotype who were male (0.60, 0.44-0.83), who did not have a history of CVD (0.65, 0.47-0.90), who were aged ≥ 65 years (0.64, 0.44-0.94), who were White (0.68, 0.51-0.91), or who had diabetes duration > 10 years (0.58, 0.35-0.95). HbA1c ≥ 8.0% was associated with CAD risk only among participants with the Hp2-2 phenotype who had a history of CVD (1.79, 1.00-3.20). No associations were found between the other HbA1c targets and CAD risk when participants with the Hp2-2 phenotype were grouped together or divided into subgroups. CONCLUSION: The differences in our results compared to our previous findings may be due to variations in the study populations and factors associated with weight loss, making it difficult to draw definitive conclusions. Our current findings should be considered in the context of hypothesis generation, and ideally, will encourage additional research in this field.

Real-Time Observation of Frustrated Ultrafast Recovery from Ionization in Nanostructured SiO_{2} Using Laser-Driven Accelerators.

Ionizing radiation interactions in matter can trigger a cascade of processes that underpin long-lived damage in the medium. To date, however, a lack of suitable methodologies has precluded our ability to understand the role that material nanostructure plays in this cascade. Here, we use transient photoabsorption to track the lifetime of free electrons (τ_{c}) in bulk and nanostructured SiO_{2} (aerogel) irradiated by picosecond-scale (10^{-12} s) bursts of x rays and protons from a laser-driven accelerator. Optical streaking reveals a sharp increase in τ_{c} from <1 ps to >50 ps over a narrow average density (ρ_{av}) range spanning the expected phonon-fracton crossover in aerogels. Numerical modeling suggests that this discontinuity can be understood by a quenching of rapid, phonon-assisted recovery in irradiated nanostructured SiO_{2}. This is shown to lead to an extended period of enhanced energy density in the excited electron population. Overall, these results open a direct route to tracking how low-level processes in complex systems can underpin macroscopically observed phenomena and, importantly, the conditions that permit them to emerge.

Ground reaction force patterns in knees with and without radiographic osteoarthritis and pain: descriptive analyses of a large cohort (the Multicenter Osteoarthritis Study).

OBJECTIVE: To compare ground reaction force patterns (GRF) during walking among legs defined by presence or absence of knee pain and/or radiographic knee osteoarthritis (ROA). METHOD: Principal component analysis extracted major modes of variation (PCs) in GRF data from the Multicenter Osteoarthritis Study during self-paced walking. Legs were categorized as pain + ROA (n = 168), ROA only (n = 303), pain only (n = 476), or control (n = 1877). Relationships between group and GRF PCs were examined using Generalized Estimating Equations, adjusted for age, sex, body mass index, race, and clinic site with and without additional adjustment for gait speed. RESULTS: With or without speed adjustment, pain + ROA had flatter vertical GRF waveforms than control (speed adjusted PC2 difference [95%CI]: -66 [-113,-20]), pain + ROA and ROA only had higher lateral GRF at impact and greater mid-stance medial GRF than control (speed adjusted PC3 difference: 9 [3,16] and 6 [2,10], respectively), and ROA only had higher early vs late medial GRF than control (speed adjusted PC2 difference: 7 [2,13]). Pain only had flatter vertical GRF waveforms and a smaller difference between anterior and posterior GRF than control only without speed adjustment. CONCLUSION: In this large sample, sustained mid-stance loading and higher impact loads were identified in legs with ROA or ROA and pain, even when adjusting for differences in gait speed and other confounders. While it remains to be seen whether these features precede or result from ROA and pain, the presence of these patterns in the speed-adjusted models could have implications on gait interventions aimed to change joint loading.

Biomechanical measures of clinician-defined unsteadiness during a forward stepdown task in individuals post-arthroscopy for femoroacetabular impingement syndrome.

BACKGROUND: Patients with femoroacetabular impingement syndrome can present with aberrant movement patterns including unsteady balance. Balance training is included in rehabilitation after hip arthroscopy and may improve quality of movement; however, specific biomechanical measures associated with clinician-defined balance impairments are unknown. We aimed to understand these associations as they may inform targeted rehabilitative interventions. METHODS: The forward stepdown is a clinical test used to evaluate movement quality, including balance. 23 individuals at least one-year post-arthroscopy for femoroacetabular impingement syndrome and 15 healthy comparisons performed the forward stepdown, recorded by 3-dimensional motion capture and 2-dimensional video. Three physical therapists graded the 2-dimensional video for steadiness. Two-way analyses of variance were used to evaluate the interaction of group (post-arthroscopy/healthy comparison) by steadiness (steady/unsteady), for center of pressure medial-lateral excursion, center of pressure path length, and lateral trunk, pelvis, and lower extremity joint excursions. FINDINGS: Six (26.1%) participants post-arthroscopy and five (33.3%) healthy comparisons were categorized as unsteady. The odds of being categorized as unsteady were not greater for participants post-arthroscopy (P = 0.72). There were no significant interactions; however, participants with clinician-defined unsteady balance, regardless of group, had significantly greater frontal plane trunk excursion, greater hip excursion, and greater center of pressure path length than those with steady balance (P ≤ 0.006). INTERPRETATION: The odds of being categorized as unsteady were not greater for individuals post-arthroscopy for femoroacetabular impingement syndrome. Clinician-defined unsteadiness was associated with greater frontal plane trunk and hip motion which may be rehabilitation targets to improve balance during a dynamic single-leg task.

Absolute calibration of Fujifilm BAS-TR image plate response to laser driven protons up to 40 MeV.

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

Test-retest reliability and minimum detectable change for various frontal plane projection angles during dynamic tasks.

OBJECTIVE: Establish between-day test-retest reliability metrics for 2-dimensional frontal plane projection angles (FPPAs) during the lateral step-down (LSD), single-limb squat (SLS), single-limb landing (SLL), and drop vertical jump (DVJ). DESIGN: Test-retest reliability study. SETTING: University laboratory. PARTICIPANTS: 20 healthy adults (12 female, age = 23.60 ±â€¯1.93 years old, body mass index = 24.26 ±â€¯2.54 kg/m2) were tested on 2 separate occasions 7-14 days apart. MAIN OUTCOME MEASURES: Intraclass correlation coefficients (ICC), standard errors of the measurement (SEM), and minimal detectable change (MDC) values across the LSD, SLS, SLL, and DVJ for the following body region variables: trunk, trunk on pelvis, pelvis, hip, thigh to vertical, knee, and shank to vertical. RESULTS: There was moderate-to-substantial between-day test-retest reliability for nearly all body regions across all tasks (ICC = 0.65-0.96). SEM values varied across body regions and tasks (0.9-3.5°). MDCs were variable (2.3-9.8°). Of the body regions, MDCs were largest for the knee and hip. By task, MDCs were lowest for the LSD. CONCLUSIONS: This study identified between-day test-retest reliability metrics for 2-dimensional FPPAs across a variety of body regions during commonly assessed clinical tasks. These data allow clinicians and researchers to more confidently assess true change between assessments or over time.

Efficient post-acceleration of protons in helical coil targets driven by sub-ps laser pulses.

The characteristics of laser driven proton beams can be efficiently controlled and optimised by employing a recently developed helical coil technique, which exploits the transient self-charging of solid targets irradiated by intense laser pulses. Here we demonstrate a well collimated (<1° divergence) and narrow bandwidth (~10% energy spread) proton beamlet of ~107 particles at 10 ± 0.5 MeV obtained by irradiating helical coil targets with a few joules, sub-ps laser pulses at an intensity of ~2 × 1019 W cm-2. The experimental data are in good agreement with particle tracing simulations suggesting post-acceleration of protons inside the coil at a rate ~0.7 MeV/mm, which is comparable to the results obtained from a similar coil target irradiated by a fs class laser at an order of magnitude higher intensity, as reported in S. Kar et al., Nat. Commun, 7, 10792 (2016). The dynamics of hot electron escape from the laser irradiated target was studied numerically for these two irradiation regimes, which shows that the target self-charging can be optimised at a pulse duration of few hundreds of fs. This information is highly beneficial for maximising the post-acceleration gradient in future experiments.

An ultra-high gain and efficient amplifier based on Raman amplification in plasma.

Raman amplification arising from the excitation of a density echelon in plasma could lead to amplifiers that significantly exceed current power limits of conventional laser media. Here we show that 1-100 J pump pulses can amplify picojoule seed pulses to nearly joule level. The extremely high gain also leads to significant amplification of backscattered radiation from "noise", arising from stochastic plasma fluctuations that competes with externally injected seed pulses, which are amplified to similar levels at the highest pump energies. The pump energy is scattered into the seed at an oblique angle with 14 J sr-1, and net gains of more than eight orders of magnitude. The maximum gain coefficient, of 180 cm-1, exceeds high-power solid-state amplifying media by orders of magnitude. The observation of a minimum of 640 J sr-1 directly backscattered from noise, corresponding to ≈10% of the pump energy in the observation solid angle, implies potential overall efficiencies greater than 10%.

Experimental measurements of the collisional absorption of XUV radiation in warm dense aluminium.

The collisional (or free-free) absorption of soft x rays in warm dense aluminium remains an unsolved problem. Competing descriptions of the process exist, two of which we compare to our experimental data here. One of these is based on a weak scattering model, another uses a corrected classical approach. These two models show distinctly different behaviors with temperature. Here we describe experimental evidence for the absorption of 26-eV photons in solid density warm aluminium (T_{e}≈1 eV). Radiative x-ray heating from palladium-coated CH foils was used to create the warm dense aluminium samples and a laser-driven high-harmonic beam from an argon gas jet provided the probe. The results indicate little or no change in absorption upon heating. This behavior is in agreement with the prediction of the corrected classical approach, although there is not agreement in absolute absorption value. Verifying the correct absorption mechanism is decisive in providing a better understanding of the complex behavior of the warm dense state.

Picosecond metrology of laser-driven proton bursts.

Tracking primary radiation-induced processes in matter requires ultrafast sources and high precision timing. While compact laser-driven ion accelerators are seeding the development of novel high instantaneous flux applications, combining the ultrashort ion and laser pulse durations with their inherent synchronicity to trace the real-time evolution of initial damage events has yet to be realized. Here we report on the absolute measurement of proton bursts as short as 3.5±0.7 ps from laser solid target interactions for this purpose. Our results verify that laser-driven ion acceleration can deliver interaction times over a factor of hundred shorter than those of state-of-the-art accelerators optimized for high instantaneous flux. Furthermore, these observations draw ion interaction physics into the field of ultrafast science, opening the opportunity for quantitative comparison with both numerical modelling and the adjacent fields of ultrafast electron and photon interactions in matter.

Fast-electron refluxing effects on anisotropic hard-x-ray emission from intense laser-plasma interactions.

Fast-electron generation and dynamics, including electron refluxing, is at the core of understanding high-intensity laser-plasma interactions. This field is itself of strong relevance to fast ignition fusion and the development of new short-pulse, intense, x-ray, γ-ray, and particle sources. In this paper, we describe experiments that explicitly link fast-electron refluxing and anisotropy in hard-x-ray emission. We find the anisotropy in x-ray emission to be strongly correlated to the suppression of refluxing. In contrast to some previous work, the peak of emission is directly along the rear normal to the target rather than along either the incident laser direction or the specular reflection direction.

A state university's model program to increase the number of its disadvantaged students who matriculate into health professions schools.

Health professions schools often provide support for minority and disadvantaged students in high school or in a single college summer program. However, long-term support for students during their undergraduate years is also crucial. Since 1990, San Diego State University (SDSU), a large urban public university, has implemented the Health Careers Opportunity Program (HCOP) to increase the number of the university's disadvantaged students (most of whom are from minority groups) who matriculate into medical, dental, veterinary, and physician assistant schools. The program's 11 components, each dedicated to some form of educational intervention and support, emphasize developing students' collaborative learning skills, fostering their pride in accomplishment, and helping them achieve positive self-images and self-confidence; these goals are linked with building students' analytical and problem-solving skills. Weekly journals kept by students' mentors serve as an "early warning system" for "bad" feelings, attitudes, and behaviors that reflect students' personal problems and correlate with lower grades, and help the program staff work intensively with students immediately, before problems become severe. The SDSU's HCOP increased the number of disadvantaged (mostly minority) students staying in the prehealth career path (not counting those in the schools of nursing and public health) from 70 in 1989 to 360 in 1995. In 1992 through 1994, the students who had completed the HCOP's Summer Academic Program (to help them bridge into a science curriculum) had pass rates for entry-level math, writing competency, and math placement that were consistently higher than the rates for other SDSU students. The overall grade-point average of HCOP students in the spring of 1995 (3.05) was significantly higher than the overall GPA of all minority students in prehealth training before the HCOP began (2.59 in 1988). The number of SDSU's minority students accepted by health professions schools (primarily medical schools) rose significantly from six in 1990 to 23 in 1995. It is clear that the labor-intensive interventions of the HCOP throughout students' years at SDSU until they matriculate into health professions schools are working.

A critical review of atomic absorption, spectrochemical, and x-ray fluorescence methods for the determination of the noble metals--II.

The review is a continuation of the initial reviews and covers the period of abstracting up to and including April, 1967. Work on the atomic-absorption determination of noble metals is also included.

Impact of diagnostic immunohistochemistry on the recognition and management of two cases of thyroid cancer with protracted courses.

This report presents two cancer cases with protracted courses in which diagnostic immunohistochemistry for thyroglobulin and/or calcitonin was performed several years after the original light microscopic interpretation. In both cases, diagnostic immunohistochemistry suggested significant changes in tumor classification. In light of current controversies and interpretive problems in this area, confirmatory tests for serum calcitonin and serum thyroglobulin and scans for iodine 131 uptake were performed. These confirmed the immunohistochemical evidence, and led to major changes in patient management. Several similar cases were found in the literature. In cancer cases with a protracted course, but with atypical or discordant clinical and/or pathologic features, diagnostic immunohistochemistry for thyroid markers may merit consideration because of the potential for meaningful changes in clinical management.

Characterisation of deuterium spectra from laser driven multi-species sources by employing differentially filtered image plate detectors in Thomson spectrometers.

A novel method for characterising the full spectrum of deuteron ions emitted by laser driven multi-species ion sources is discussed. The procedure is based on using differential filtering over the detector of a Thompson parabola ion spectrometer, which enables discrimination of deuterium ions from heavier ion species with the same charge-to-mass ratio (such as C(6+), O(8+), etc.). Commonly used Fuji Image plates were used as detectors in the spectrometer, whose absolute response to deuterium ions over a wide range of energies was calibrated by using slotted CR-39 nuclear track detectors. A typical deuterium ion spectrum diagnosed in a recent experimental campaign is presented, which was produced from a thin deuterated plastic foil target irradiated by a high power laser.

Electron refluxing and K-shell line emission from Ti foils irradiated with subpicosecond laser pulses at 527 nm.

We present data on emission of K-shell radiation from Ti foils irradiated with subpicosecond pulses of second harmonic radiation (527 nm) from the TARANIS laser system at intensities of up to 10(18) W cm(-2). The data are used to demonstrate that a resonance absorption type mechanism is responsible for absorption of the laser light and to estimate fast electron temperatures of 30-60 keV that are in broad agreement with expectation from models of absorption for a steep density gradient. Data taken with resin-backed targets are used to demonstrate clear evidence of electron refluxing even at the modest fast electron temperatures inferred.

Learning chronobiology by improving Wikipedia.

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.