Multi-scale time-resolved electron diffraction: A case study in moiré materials.

Ultrafast-optical-pump - structural-probe measurements, including ultrafast electron and x-ray scattering, provide direct experimental access to the fundamental timescales of atomic motion, and are thus foundational techniques for studying matter out of equilibrium. High-performance detectors are needed in scattering experiments to obtain maximum scientific value from every probe particle. We deploy a hybrid pixel array direct electron detector to perform ultrafast electron diffraction experiments on a WSe2/MoSe2 2D heterobilayer, resolving the weak features of diffuse scattering and moiré superlattice structure without saturating the zero order peak. Enabled by the detector's high frame rate, we show that a chopping technique provides diffraction difference images with signal-to-noise at the shot noise limit. Finally, we demonstrate that a fast detector frame rate coupled with a high repetition rate probe can provide continuous time resolution from femtoseconds to seconds, enabling us to perform a scanning ultrafast electron diffraction experiment that maps thermal transport in WSe2/MoSe2 and resolves distinct diffusion mechanisms in space and time.

Single-Crystal Alkali Antimonide Photocathodes: High Efficiency in the Ultrathin Limit.

The properties of photoemission electron sources determine the ultimate performance of a wide class of electron accelerators and photon detectors. To date, all high-efficiency visible-light photocathode materials are either polycrystalline or exhibit intrinsic surface disorder, both of which limit emitted electron beam brightness. In this Letter, we demonstrate the synthesis of epitaxial thin films of Cs_{3}Sb on 3C-SiC (001) using molecular-beam epitaxy. Films as thin as 4 nm have quantum efficiencies exceeding 2% at 532 nm. We also find that epitaxial films have an order of magnitude larger quantum efficiency at 650 nm than comparable polycrystalline films on Si. Additionally, these films permit angle-resolved photoemission spectroscopy measurements of the electronic structure, which are found to be in good agreement with theory. Epitaxial films open the door to dramatic brightness enhancements via increased efficiency near threshold, reduced surface disorder, and the possibility of engineering new photoemission functionality at the level of single atomic layers.

A kiloelectron-volt ultrafast electron micro-diffraction apparatus using low emittance semiconductor photocathodes.

We report the design and performance of a time-resolved electron diffraction apparatus capable of producing intense bunches with simultaneously single digit micrometer probe size, long coherence length, and 200 fs rms time resolution. We measure the 5d (peak) beam brightness at the sample location in micro-diffraction mode to be 7 × 10 13 A / m 2 rad 2 . To generate high brightness electron bunches, the system employs high efficiency, low emittance semiconductor photocathodes driven with a wavelength near the photoemission threshold at a repetition rate up to 250 kHz. We characterize spatial, temporal, and reciprocal space resolution of the apparatus. We perform proof-of-principle measurements of ultrafast heating in single crystal Au samples and compare experimental results with simulations that account for the effects of multiple scattering.

The relationship of 25-hydroxyvitamin D values and risk of fracture: a population-based retrospective cohort study.

Our study investigates 25-hydroxyvitamin D levels and fracture risk using population-level data. 25-Hydroxyvitamin D values < 12, 12-19, and > 50 ng/mL were not associated with increased risk of fractures overall compared with values 20-50 ng/mL. Severely low levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist. INTRODUCTION: Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and fracture risk have been inconsistent. We hypothesized that high 25(OH)D concentrations (> 50 ng/mL) would be associated with increased risk of fracture. METHODS: We identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005 and December 31, 2011, who had at least one 25(OH)D measurement. Fracture outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients' final clinical visit as an Olmsted County resident, December 31, 2014, or death. Data were analyzed using Cox proportional hazard regression. RESULTS: Of 11,002 individuals with a 25(OH)D measurement, 5.8% had a 25(OH)D value ˂ 12 ng/mL, and 5.1% had a value > 50 ng/mL. Compared with subjects with 25(OH)D values 20-50 ng/mL (reference group), values < 12, 12-19, and > 50 ng/mL displayed no association with overall fracture risk. After adjusting for a prior diagnosis of osteoporosis/osteopenia, only individuals with values ˂ 12 ng/mL had increased risk of any osteoporotic fracture (aHR = 1.41; 95% CI 1.05-1.89) and wrist fracture (aHR = 2.11; 95% CI 1.27-3.48) compared with the reference group. Compared with the reference group, values ˂ 12 ng/mL were associated with increased risk of any fracture (aHR = 1.35; 95% CI 1.01-1.80), osteoporotic fracture (aHR = 2.18; 95% CI 1.44-3.31), and wrist fracture (aHR = 2.39; 95% CI 1.19-4.81) in subjects without a prior diagnosis of osteoporosis/osteopenia, but not in those with a prior diagnosis of osteoporosis/osteopenia. CONCLUSION: Severely low 25(OH)D levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist, but 25(OH)D values > 50 ng/mL were not associated with increased fracture risk.

Development of a 3-D energy-momentum analyzer for meV-scale energy electrons.

In this article, we report on the development of a time-of-flight based electron energy analyzer capable of measuring the 3-D momentum and energy distributions of very low energy (millielectronvolt-scale) photoemitted electrons. This analyzer is capable for measuring energy and 3-D momentum distributions of electrons with energies down to 1 meV with a sub-millielectronvolt energy resolution. This analyzer is an ideal tool for studying photoemission processes very close to the photoemission threshold and also for studying the physics of photoemission based electron sources.

Enhanced energy gain in a dielectric laser accelerator using a tilted pulse front laser.

Using an 800 nm, 45 fs pulse-front-tilted laser we demonstrate a record 315 keV energy gain in a dual grating dielectric laser accelerator (DLA) and average accelerating gradients of 560 MV/m over 0.5 mm. These results open a new regime in DLA characterized by significant evolution of the beam distribution in the longitudinal phase space, corresponding to > 1/4 of a synchrotron oscillation. By tilting the laser wavefront we control the resonant velocity of the DLA and observe a net energy gain, indicating that a tapered optical phase could be used to achieve very high energy gain.

The Effectiveness of a Family-Centered Childhood Obesity Intervention at the YMCA: A Pilot Study.

OBJECTIVE: Community-based, family-centered obesity prevention/treatment initiatives have been shown to be effective in reducing body mass index (BMI) and improving healthy habits in children if implemented with high intensity and sufficient duration. Let's Go! 5-2-1-0 Program (5-2-1-0) was incorporated into family-centered, monthly physical activity classes and cooking classes over six months delivered by Young Men's Christian Association (YMCA) staff. We hypothesized that implementation of this intervention would improve 5-2-1-0 knowledge attainment, increase healthy behavior (based on 5- 2-1-0 curriculum), and improve BMI and waist circumference measurements in children. METHODS: Children attending YMCA summer camps in Rochester, MN, during 2016 were recruited via study packets mailed to their families. Height, weight, and waist circumference measurements as well as the results of the Modified Healthy Habits Survey and the 5-2-1-0 Knowledge Acquisition Survey were recorded for each participating child at baseline and 6-month follow-up. The intervention group received monthly healthy habit reminder emails, and was invited to monthly evening cooking and physical activity classes for 7 sessions over a 6-month period. RESULTS: Fifteen families in the intervention group attended classes. Of those, 13 families regularly participated in (attended at least 5 out of 7) both the monthly physical activity and cooking classes. The children in the intervention group had a significant improvement in the number of Knowledge Acquisition Survey questions answered correctly (p<0.001), while there was no improvement in the control group. As compared to children in the control group, there was no significant change in BMI or waist circumference or healthy habits in the intervention group. CONCLUSION: Our study findings indicate that our intervention resulted in improved knowledge about healthy habits, but did not significantly impact healthy habits or BMI. Potential reasons for this were the small sample size and the attenuated length and/or intensity of the intervention.

Meter-Scale Terahertz-Driven Acceleration of a Relativistic Beam.

Terahertz (THz) radiation promises breakthrough advances in compact advanced accelerators due to the gigavolts-per-meter fields achievable, but the challenge of maintaining overlap and synchronism between beams and short laser-generated THz pulses has so far limited interactions to the few-millimeter scale. We implement a novel scheme for simultaneous group and phase velocity matching of nearly single-cycle THz radiation with a relativistic electron beam for meter-scale inverse free-electron laser interaction in a magnetic undulator, resulting in energy modulations of up to 150 keV using modest THz pulse energies (≤1 µJ). Using this scheme, we demonstrate for the first time the use of a laser-based THz source for bunch-length compression and time-stamping of a relativistic electron beam.

Double-shot MeV electron diffraction and microscopy.

In this paper, we study by numerical simulations a time-resolved MeV electron scattering mode where two consecutive electron pulses are used to capture the evolution of a material sample on 10 ps time scales. The two electron pulses are generated by illuminating a photocathode in a radiofrequency photogun by two short laser pulses with adjustable delay. A streak camera/deflecting cavity is used after the sample to project the two electron bunches on two well separated regions of the detector screen. By using sufficiently short pulses, the 2D spatial information from each snapshot can be preserved. This "double-shot" technique enables the efficient capture of irreversible dynamics in both diffraction and imaging modes. In this work, we demonstrate both modes in start-to-end simulations of the UCLA Pegasus MeV microscope column.

Demonstration of Single-Shot Picosecond Time-Resolved MeV Electron Imaging Using a Compact Permanent Magnet Quadrupole Based Lens.

We present the results of an experiment where a short focal length (∼1.3 cm), permanent magnet electron lens is used to image micron-size features (of a metal sample) with a single shot from an ultrahigh brightness picosecond-long 4 MeV electron beam emitted by a radio-frequency photoinjector. Magnification ratios in excess of 30× were obtained using a triplet of compact, small gap (3.5 mm), Halbach-style permanent magnet quadrupoles with nearly 600 T/m field gradients. These results pave the way towards single-shot time-resolved electron microscopy and open new opportunities in the applications of high brightness electron beams.

US Preventative Services Task Force FRAX threshold has a low sensitivity to detect osteoporosis in women ages 50-64 years.

UNLABELLED: The US Preventative Services Task Force (USPSTF) recommends consideration for screening for osteoporosis in women under age 65 who have an estimated 10-year major osteoporotic fracture risk of 9.3 % or higher. We found that this threshold for osteoporosis screening in women ages 50-64 years old has a low sensitivity to detect osteoporosis. INTRODUCTION: The US Preventative Services Task Force (USPSTF) recommends consideration of dual-energy X-ray absorptiometry (DXA) in women under ages 50-64 with a major osteoporotic fracture (MOF) risk of 9.3 % or higher, as estimated by the fracture risk assessment tool (FRAX) tool. We assessed the performance of the 9.3 % MOF risk threshold for detecting osteoporosis and evaluated whether DXA indication appeared appropriate, based on USPSTF criteria and other risk factors, at our institution. METHODS: We performed a retrospective record review of women ages 50-64.5 years old to determine clinical factors and FRAX scores of women undergoing a DXA at our institution over a 6-month period after the USPSTF recommendations were released and evaluated the sensitivity and specificity of the 9.3 % MOF threshold to detect densitometric osteoporosis. Additionally, using the USPSTF criteria and several additional risk factors, we evaluated the extent of potentially inappropriate DXA use in women ages 50 to 64 years in a large primary care practice in an academic medical center. RESULTS: The analysis included 465 DXA tests. The overall sensitivity and specificity of a FRAX-calculated MOF risk ≥9.3 % was 37 and 74 %, respectively, for the detection of osteoporosis. The receiver operator characteristic curve (ROC) demonstrated an area under the curve of 0.58. Lowering the FRAX risk threshold to 5.5 % would increase the sensitivity of detecting osteoporosis in our population from 37 to 80 % while reducing the specificity from 74 to 27 %. Out of 465 DXAs, 371 (79.8 %) were classified as appropriately ordered per our pre-specified criteria. Of the 120 women with osteoporosis at the hip and/or spine based on T-score values of -2.5 or less, 14 DXAs (11.7 %) were classified as potentially inappropriate based on a FRAX-predicted MOF risk less than 9.3 % and lack of additional pre-specified risk factors. CONCLUSION: We found that the USPSTF-recommended MOF risk threshold of 9.3 % for osteoporosis screening in women ages 50-64 years old has a low sensitivity to detect osteoporosis.

Implementing Child-focused Activity Meter Utilization into the Elementary School Classroom Setting Using a Collaborative Community-based Approach.

INTRODUCTION: The prevalence of pediatric obesity has increased over the past 3 decades and is a pressing public health program. New technology advancements that can encourage more physical in children are needed. The Zamzee program is an activity meter linked to a motivational website designed for children 8-14 years of age. The objective of the study was to use a collaborative approach between a medical center, the private sector and local school staff to assess the feasibility of using the Zamzee Program in the school-based setting to improve physical activity levels in children. METHODS: This was a pilot 8-week observational study offered to all children in one fifth grade classroom. Body mass index (BMI), the amount of physical activity by 3-day recall survey, and satisfaction with usability of the Zamzee Program were measured pre- and post-study. RESULTS: Out of 11 children who enrolled in the study, 7 completed all study activities. In those who completed the study, the median (interquartile range) total activity time by survey increased by 17 (1042) minutes and the BMI percentile change was 0 (8). Both children and their caregivers found the Zamzee Activity Meter (6/7) and website (6/7) "very easy" or "easy" to use. CONCLUSION: The Zamzee Program was found to be usable but did not significantly improve physical activity levels or BMI. Collaborative obesity intervention projects involving medical centers, the private sector and local schools are feasible but the effectiveness needs to be evaluated in larger-scale studies.

CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia.

Truncation mutations of the receptor cytoplasmic domain for colony-stimulating factor 3 (CSF3R) are frequently seen in severe congenital neutropenia, whereas activating missense mutations affecting the extracellular domain (exon 14) have been described in hereditary neutrophilia and chronic neutrophilic leukemia (CNL). In order to clarify mutational frequency, specificity and phenotypic associations, we sequenced CSF3R exons 14-17 in 54 clinically suspected cases of CNL (n=35) or atypical chronic myeloid leukemia (aCML; n=19). Central review of these cases confirmed WHO-defined CNL in 12 patients, monoclonal gammopathy (MG)-associated CNL in 5 and WHO-defined aCML in 9. A total of 14 CSF3R mutations were detected in 13 patients, including 10 with CSF3RT618I (exon 14 mutation, sometimes annotated as CSF3R T595I). CSF3RT618I occurred exclusively in WHO-defined CNL with a mutational frequency of 83% (10 of 12 cases). CSF3R mutations were not seen in aCML or MG-associated CNL. CSF3RT618I was also absent among 170 patients with primary myelofibrosis (PMF; n=76) or chronic myelomonocytic leukemia (CMML; n=94). SETBP1 mutational frequencies in WHO-defined CNL, aCML, CMML and PMF were 33, 0, 7 and 3%, respectively. Four CSF3RT618I-mutated cases co-expressed SETBP1 mutations. We conclude that CSF3RT618I is a highly sensitive and specific molecular marker for CNL and should be incorporated into current diagnostic criteria.

Autism, early narcissistic injury and self-organization: a role for the image of the mother's eyes?

Holland elucidated the new paradigm of self-organization in complex adaptive systems. This paradigm holds for all living systems, including the personality. In conjunction with the theory of archetypes, self-organization suggests two radical hypotheses, one about early development, the other about the origins of autism. Autism is associated with several medical conditions, with genetic markers, and with infant visual deprivation. However none of these factors is either necessary or sufficient to cause autism. It is hypothesized that each of these factors increases the likelihood of a primary psychological deficit: failure to acquire, or retain, the image of the mother's eyes. This hypothesis was initially derived from analytic work with patients who have early narcissistic injury and with patients who have mild autistic traits. Both diagnoses may arise from the same initial disturbance: Symington argued that autism is an extreme form of infantile narcissism. Indirect evidence for the image-of-the-eyes hypotheses comes from the evolution of primates, from infant-mother observations, from observations of infant vision, and from experiments on vision in other vertebrates. Byrd recently confirmed that the incidence of autism is increasing dramatically. The image-of-the-eyes hypotheses suggest that this increase may be linked to increased use of non-maternal childcare for young infants.

Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols.

The cell injury caused by oxidized lipoproteins was among the first findings that led to the theory that it is the oxidation of low-density lipoprotein (LDL), not just LDL concentration, that leads to arterial disease. Voluminous studies have now revealed that oxidized lipoproteins and their constituents can induce numerous effects on cells that can be construed to be atherogenic. Cell injury is but one of these, and it is these injurious effects that are the focus of this brief review. Cell injury and death appear to play multiple roles in lesion development and the toxic lipid constituents of oxidized lipoproteins, including a variety of oxysterols, are candidates for the in vivo effectors of this cytotoxicity. Recent studies have focused on the mechanisms of oxidized lipoprotein-induced cell death, whether the cells die by apoptosis or necrosis, and the identities of the toxins that induce injury. Understanding the roles of these agents in lesion development could lead to therapies that modulate cell death and inhibit lesion formation.

Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a retrospective comparative study of single-agent dosages.

PURPOSE: The aim of this study was to evaluate the relative activity and tolerance of liposomal doxorubicin in recurrent ovarian, peritoneal, and tubal carcinoma at an initial dose of 40 or 50 mg/m(2) every 4 weeks. METHODS: A retrospective single-institution study was performed on patients who received liposomal doxorubicin from 1/97 to 12/00. Demographic data, liposomal doxorubicin dose, dose reductions, response, and progression-free and overall survival were recorded. RESULTS: Seventy-eight patients, 38 treated at 40 mg/m(2) and 40 treated at 50 mg/m(2), were identified. There was no difference with respect to patient age, performance status, percentage of patients who were platinum resistant or paclitaxel resistant, or tumor bulk. The response rate in this highly resistant population was 13.5 and 7.7% for liposomal doxorubicin at 40 and 50 mg/m(2) every 4 weeks, respectively. Stable disease was observed in 49 and 51% of patients treated with liposomal doxorubicin at a dose of 40 and 50 mg/m(2) every 4 weeks, respectively. The progression-free survival for patients with responding and stable disease was similar. Dose reductions were required in 27.5% of patients treated at 50 mg/m(2) versus no patients treated at 40 mg/m(2) (P < 0.001). Treatment delays due to toxicity were required in 32.5% of patients treated at 50 mg/m(2) versus 16% of patients treated at 40 mg/m(2) (P = 0.14). CONCLUSION: Liposomal doxorubicin at a dose of 40 mg/m(2) appears to be as active as liposomal doxorubicin at a dose of 50 mg/m(2) in ovarian, peritoneal, and tubal carcinoma and is better tolerated based on the frequency of dose reductions and treatment delays.

Management of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a complex condition in which diffuse clotting and profuse hemorrhaging occur simultaneously. It is a serious, often fatal, condition that is estimated to occur in approximately 10% of all patients diagnosed with cancer. No single laboratory test is available that is absolutely diagnostic for DIC; however, several laboratory results, combined with certain clinical findings, will support the diagnosis. Despite the lack of a standardized protocol for clinical management, aggressive medical and nursing care can play a prominent role in the clinical outcome of the patient with DIC.

New isolation technique to study apoptosis in human intestinal epithelial cells.

Intestinal epithelial cells derive from stem cells at the base of the crypt and migrate along the crypt-lumen axis. Their life is terminated as they reach the luminal surface where they detach and are shed. Intestinal epithelial cells show evidence of apoptosis in the region of shedding, and cell death is thought to resemble a form of apoptosis called detachment-induced cell death, or anoikis. Human intestinal epithelial cells die rapidly in vitro due to loss of anchorage during isolation, making primary culture of these cells a goal that has not yet been reached. However, the molecular mechanisms underlying this process of anoikis are largely unknown. In this study, a novel protocol for the rapid, temperature-controlled isolation of highly purified human colonic epithelial cells from surgical specimens is described. Using this method, early molecular events of anoikis in nontransformed epithelial cells were studied. Intestinal epithelial cells were isolated at the beginning of the apoptotic cascade, before the activation of caspase 3 family members and cleavage of poly(ADP-ribose) polymerase and DNA fragmentation. Elucidating the molecular mechanisms of detachment-induced cell death may facilitate the establishment of long-term primary cultures of human intestinal epithelial cells and enhance our understanding of homeostasis in the intestinal epithelium.

Cloning of a DNA-binding protein that interacts with the ethylene-responsive enhancer element of the carnation GST1 gene.

Ethylene transcriptionally activates a glutathione S-transferase gene (GST1) at the onset of the senescence program in carnation (Dianthus caryophyllus L.) flower petals. A 126 bp region of the GST1 promoter sequence has been identified as an ethylene-responsive enhancer element (ERE). In this paper, we demonstrate the ability of nuclear proteins from senescing petals to recognize a 22 bp sequence within the ERE (ERE oligonucleotide). Mutation of the ERE oligonucleotide sequence significantly alters the strength of this nuclear protein-DNA association. The wild-type ERE oligonucleotide sequence was used to isolate a cDNA clone encoding a sequence-specific DNA binding protein. Nucleotide sequencing and deduced amino acid sequence analysis of this cDNA predicted a 32 kDa protein which we have designated carnation ethylene-responsive element-binding protein-1 (CEBP-1). The mRNA expression pattern of CEBP-1 suggests that it is not transcriptionally regulated by ethylene. The amino acid sequence homology of CEBP-1 with other plant nucleic acid binding proteins indicates a conserved nucleic acid binding domain. Within this domain are two highly conserved RNA-binding motifs, RNP-1 and RNP-2. An acidic region and a putative nuclear localization signal are also identified.