Objective:
Between 31 and 35% of the college‐aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, ...acceptability, and initial efficacy of a technology‐based 8‐week weight loss intervention among college students.
Design and Methods:
Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post‐treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m2. Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races).
Results:
The primary outcome was weight loss after 8 weeks (post‐treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (−2.4 ± 2.5 kg) than the Facebook (−0.63 ± 2.4 kg) and Waiting List (−0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups.
Conclusions:
Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.
Between 31 and 35% of the college-aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and ...initial efficacy of a technology-based 8-week weight loss intervention among college students. Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post-treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m2. Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races). The primary outcome was weight loss after 8 weeks (post-treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (-2.4 ± 2.5 kg) than the Facebook (-0.63 ± 2.4 kg) and Waiting List (-0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups. Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.
Chemical genetic screening of small-molecule libraries has been a promising strategy for discovering unique and novel therapeutic compounds. However, identifying the targets of lead molecules that ...arise from these screens has remained a major bottleneck in understanding the mechanism of action of these compounds. Here, we have coupled the screening of a cysteine-reactive fragment-based covalent ligand library with an isotopic tandem orthogonal proteolysis-enabled activity-based protein profiling (isoTOP-ABPP) chemoproteomic platform to rapidly couple the discovery of lead small molecules that impair pancreatic cancer pathogenicity with the identification of druggable hotspots for potential cancer therapy. Through this coupled approach, we have discovered a covalent ligand DKM 2–93 that impairs pancreatic cancer cell survival and in vivo tumor growth through covalently modifying the catalytic cysteine of the ubiquitin-like modifier activating enzyme 5 (UBA5), thereby inhibiting its activity as a protein that activates the ubiquitin-like protein UFM1 to UFMylate proteins. We show that UBA5 is a novel pancreatic cancer therapeutic target and show DKM 2–93 as a relatively selective lead inhibitor of UBA5. Our results underscore the utility of coupling the screening of covalent ligand libraries with isoTOP-ABPP platforms for mining the proteome for druggable hotspots for cancer therapy.
The late Paleozoic Ice Age (LPIA) was one of Earth's most important Phanerozoic climatic events lasting for over 100 Mys. Despite its importance, its history is controversial with two hypotheses that ...portray glaciation differently (Fig. 1). Traditional views characterize the LPIA as a continuous glacial event that lasted from the Middle Mississippian until the Late Permian with a massive ice sheet that covered Gondwana throughout this interval. This approach often uses only one or two proxies to define the glaciation. The other emerging hypothesis suggests that numerous ice sheets occurred in Gondwana with individual glacial events lasting up to 10 Mys alternating with glacial minima/non-glacial intervals of similar duration. Both views are still prevalent. Both near- and far-field proxies are used to define the ice age. Near-field proxies include the occurrence/absence of diamictites, glaciotectonic deposits/landforms, striated clasts and clast pavements, outsized clasts (dropstones), rhythmites, cyclic diamictite-bearing successions, glendonites, grooved and striated surfaces, streamline landforms, and U-shaped paleovalleys. Detrital zircons and chemical index of alteration (CIA) studies help to delineate the occurrence, extent, and location of glaciation. Multiple complexities occur with the use of these proxies as different non-glacial processes and driving factors can produce similar features or results. Far-field proxies focus on identifying changes in eustacy. These include the occurrence of cyclic successions composed of alternating nonmarine and marine strata (cyclothems), depth of incised valleys, paleotopographic relief, phosphatic black shales, and changing oxygen isotope ratios. Like the near-field record, far-field proxies are complex indicators with varied nuances that make their application challenging. Here we discuss the limitations and use of these proxies and promote a multiproxy approach to investigating Earth's glacial intervals. We suggest that studies incorporate multiple proxies coupled with detailed environmental, paleoflow, and paleogeographic analyses to better constrain the occurrence, timing, and extent of glaciation and its influence on global systems. This approach will provide a robust view of the LPIA. We also consider the magnitude and nature of sea-level response to changing ice volumes by discussing ice-volume fluctuations, basin subsidence's modification of glacioeustacy, and sea-level's response to global isostatic adjustment (GIA). In considering these features, it becomes apparent that glacioeustacy is more complex than previously envisioned.
Estrogen Therapy and Coronary-Artery Calcification Manson, JoAnn E; Allison, Matthew A; Rossouw, Jacques E ...
New England journal of medicine/The New England journal of medicine,
06/2007, Letnik:
356, Številka:
25
Journal Article
Recenzirano
Odprti dostop
In the previously published Women's Health Initiative comparing conjugated equine estrogens with placebo in women who had undergone hysterectomy, there was a substantially lower rate of events ...related to coronary heart disease among the women receiving estrogen. The current substudy showed that coronary-artery calcium scores were lower in women receiving estrogen than in those receiving placebo. Since estrogen has complex effects, the new findings should not be construed as being clinically directive.
In a previous study in women who had undergone hysterectomy, there was a substantially lower rate of events related to coronary heart disease among the women receiving estrogen. This current substudy showed that coronary-artery calcium scores were lower in women receiving estrogen than in those receiving placebo.
Although it has been hypothesized that postmenopausal estrogen therapy delays atherosclerosis,
1
–
3
recent findings from randomized clinical trials have cast doubt on a cardioprotective role of exogenous estrogen. The Women's Health Initiative (WHI) trial of conjugated equine estrogens, administered to postmenopausal women who had undergone hysterectomy, reported a hazard ratio of 0.95 (95% confidence interval CI, 0.79 to 1.16) for nonfatal myocardial infarction plus fatal coronary heart disease (CHD) among women receiving conjugated equine estrogens as compared with those receiving placebo, but secondary analyses according to age group suggested that the results differed in younger women.
4
,
5
The corresponding hazard . . .
Background
Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen‐Alone (E‐Alone) trial, randomization to conjugated equine estrogen‐alone versus placebo was ...associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI‐CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post‐trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.
Methods and Results
WHI‐CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age‐adjusted rates/1000 person‐years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2‐fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen–alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.
Conclusions
Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E‐Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen–alone versus placebo or CVD risk factors.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.
Aim
Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of ...biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study.
Method
A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90‐patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964).
Results
The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh‐specific complications occurred. Thirty‐one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re‐access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns.
Conclusion
Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials.
We have developed a diagnostic system that measures the spectrally integrated (i.e. the total) energy and power radiated by a pulsed blackbody x-ray source. The total-energy-and-power (TEP) ...diagnostic system is optimized for blackbody temperatures between 50 and 350 eV. The system can view apertured sources that radiate energies and powers as high as 2 MJ and 200 TW, respectively, and has been successfully tested at 0.84 MJ and 73 TW on the Z pulsed-power accelerator. The TEP system consists of two pinhole arrays, two silicon-diode detectors, and two thin-film nickel bolometers. Each of the two pinhole arrays is paired with a single silicon diode. Each array consists of a 38×38 square array of 10-μm -diameter pinholes in a 50-μm -thick tantalum plate. The arrays achromatically attenuate the x-ray flux by a factor of ∼1800 . The use of such arrays for the attenuation of soft x rays was first proposed by Turner and co-workers Rev. Sci. Instrum. 70, 656 (1999). The attenuated flux from each array illuminates its associated diode; the diode’s output current is recorded by a data-acquisition system with 0.6-ns time resolution. The arrays and diodes are located 19 and 24 m from the source, respectively. Because the diodes are designed to have an approximately flat spectral sensitivity, the output current from each diode is proportional to the x-ray power. The nickel bolometers are fielded at a slightly different angle from the array-diode combinations, and view (without pinhole attenuation) the same x-ray source. The bolometers measure the total x-ray energy radiated by the source and—on every shot—provide an in situ calibration of the array-diode combinations. Two array-diode pairs and two bolometers are fielded to reduce random uncertainties. An analytic model (which accounts for pinhole-diffraction effects) of the sensitivity of an array-diode combination is presented.
PDF
