Abdominal vacuum lift as an aid to diagnosing abdominal adhesions

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2006.Includes bibliographical references (leaves 18-22).The internal organs are designed to move freely and slide over one another during normal body movement. The abdominal organs, however, have a tendency to adhere to the abdominal cavity (peritoneum) and other abdominal organs after surgery or infection. These adhesions can cause pain, discomfort , inflammation, anxiety, depression, problems with conception, trouble eating, and decreased immune function. There are around 300,000 hospital admissions in the U.S. every year for patients due to adhesions.. Part of the problem is that there is no suitable method to diagnose adhesions. Recently there have been a number of studies which suggest that measuring visceral slides under ultrasound using exaggerated respiration may prove to be very promising in diagnosing adhesions non invasively. Yet there are still weaknesses in the predictive power of these procedures. For such procedures to be successfully implemented into clinical medicine and offer non invasive methods to diagnosing adhesions, they must first be able to offer higher percentage predictive values. We have worked on a number of models of an external abdominal vacuum system which we believe will increase the accuracy and predictive values of measuring visceral slides under ultrasound using exaggerated respiration.by Julius Strauss.S.B

Observations of Grizzly Bear (Ursus arctos) associated with abundance of spawning Kokanee (Oncorhynchus nerka) at an inland river, British Columbia, Canada

Salmon (Oncorhynchus spp.) are an important food source for Grizzly Bear (Ursus arctos), but many salmon populations are declining. While most research on Grizzly Bear–salmon interactions occurs in coastal ecosystems, declining salmon may also affect Grizzly Bears in inland ecosystems where salmon are also an important part of their diet. We document changes in the number and distribution of observations of Grizzly Bears and changing Kokanee (i.e., landlocked Sockeye Salmon, Oncorhynchus nerka) abundance at an inland river. We hypothesized that reduced abundance of Kokanee would limit the number of Grizzly Bear observations at the river. We compared Kokanee abundance and Grizzly Bear observations (n = 535) between 2012 and 2019 at the Lardeau River, British Columbia, Canada. We used a generalized linear mixed model to test if the number of bear observations changed as a function of Kokanee abundance among four river reaches during eight consecutive years of study. Kokanee abundance was a strong statistical predictor of Grizzly Bear observations (β = 0.52, P = 0.001, CI = 0.12–0.87), and Kokanee abundance and reach explained 73% of the variance. Our results suggest that reduced Kokanee abundance also reduces Grizzly Bear presence, likely because bears seek out other, more available food sources, away from Kokanee spawning habitat. This pattern could limit ecosystem services provided by Grizzly Bears adjacent to spawning areas and it could have implications for bear management and conservation

First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma

BACKGROUND: In preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab. METHODS: In the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy. Patients received M9241 at 4, 8, 12, or 16.8 µg/kg every 4 weeks (Q4W) plus avelumab 10 mg/kg every 2 weeks (Q2W, dose levels (DLs) 1-4) or M9241 16.8 µg/kg Q4W plus avelumab 800 mg once a week for 12 weeks followed by Q2W (DL5/dose expansion). Primary endpoints for the dose-escalation part were adverse events (AEs) and dose-limiting toxicities (DLTs), and those for the dose-expansion part were confirmed best overall response (BOR) per investigator (Response Evaluation Criteria in Solid Tumors V.1.1) and safety. The dose-expansion part followed a two-stage design; 16 patients were enrolled and treated in stage 1 (single-arm part). A futility analysis based on BOR was planned to determine whether stage 2 (randomized controlled part) would be initiated. RESULTS: At data cut-off, 36 patients had received M9241 plus avelumab in the dose-escalation part. All DLs were well tolerated; one DLT occurred at DL3 (grade 3 autoimmune hepatitis). The maximum-tolerated dose was not reached, and DL5 was declared the recommended phase II dose, considering an observed drug-drug interaction at DL4. Two patients with advanced bladder cancer (DL2 and DL4) had prolonged complete responses. In the dose-expansion part, no objective responses were recorded in the 16 patients with advanced UC; the study failed to meet the criterion (≥3 confirmed objective responses) to initiate stage 2. Any-grade treatment-related AEs occurred in 15 patients (93.8%), including grade ≥3 in 8 (50.0%); no treatment-related deaths occurred. Exposures for avelumab and M9241 concentrations were within expected ranges. CONCLUSIONS: M9241 plus avelumab was well tolerated at all DLs, including the dose-expansion part, with no new safety signals. However, the dose-expansion part did not meet the predefined efficacy criterion to proceed to stage 2

The Last Waltz

Hear how the music is calling to youTelling its passion so tender and true,Each swelling measure calling to pleasure,Flooding with ardor, with heart beating harder.Melodies golden, lilting and light,Measures unfolding, joyous and bright,hear how they\u27re calling to you tonight,Calling to dance in radiant delight. REFRAINFor this may be the last waltz,That love will grant to youThe last the sweetest dream waltz,Where in our dreams come trueOh, dear and wondrous last waltz,You lure us as we part,Oh, cruel taunting last waltz,You break my longing heart. For heart. Wondrous, compelling the melody seemsTempting and burning our hearts to their dreams,Murmuring measure promising pleasure,Singing their songs of joys that we treasure. Dance with your loved one, dance while you can,Lilt with your rhythm, maiden and man,Life so enduring with all it\u27s charms

Blood pressure reduction and clinical outcomes with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: protocol for a systematic review and meta-regression analysis

Background Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) efficaciously reduce systolic blood pressure (BP), a well-established risk factor for myocardial infarction (MI). Both inhibit the renin-angiotensin system, albeit through different mechanisms, and produce similar reductions in BP. However, in parallel meta-analyses of ACEi and ARB trials, ACEis reduce risk of MI whereas ARBs do not—a phenomenon described as the ‘ARB-MI paradox’. In addition, ACEis reduce all-cause mortality, whereas ARBs do not, which appears to be independent of BP lowering. The divergent cardiovascular effects of ACE inhibitors and ARBs, despite similar BP reductions, are counter-intuitive. This systematic review aims to ascertain the extent to which clinical outcomes in randomised trials of ACEi and ARBs are attributable to reductions in systolic BP. Methods A comprehensive search of bibliographic databases will be performed to identify all randomised studies of agents of the ACEi and ARB class. Placebo and active comparator-controlled studies that report clinical outcomes, with greater than 500 person-years of follow-up in each study arm, will be included. Two independent reviewers will screen study records against a priori-defined eligibility criteria and perform data extraction. The Cochrane Risk of Bias Tool will be applied to all included studies. Studies retracted subsequent to initial publication will be excluded. Primary outcomes of interest include MI and all-cause mortality; secondary outcomes include stroke, heart failure, revascularisation and cardiovascular mortality. Meta-regression will be performed, evaluating the relationship between attained reduction in systolic BP and relative risk of each outcome, stratified by drug class. Where a BP-dependent effect exists (two-tailed p value < 0.05), relative risks, standardised per 10 mmHg difference in BP, will be reported for each study outcome. Publication bias will be examined using Funnel plots, and calculation of Egger’s statistic. Discussion This systematic review will provide a detailed synthesis of evidence regarding the relationship between BP reduction and clinical outcomes with ACEi and ARBs. Greater understanding of the dependency of the effect of each class on BP reduction will advance insight into the nature of the ARB-MI paradox and guide the future usage of these agents. Systematic review registration PROSPERO CRD4201707298

Simple Ways to Measure Behavioral Responses of Drosophila to Stimuli and Use of These Methods to Characterize a Novel Mutant

The behavioral responses of adult Drosophila fruit flies to a variety of sensory stimuli – light, volatile and non-volatile chemicals, temperature, humidity, gravity, and sound - have been measured by others previously. Some of those assays are rather complex; a review of them is presented in the Discussion. Our objective here has been to find out how to measure the behavior of adult Drosophila fruit flies by methods that are inexpensive and easy to carry out. These new assays have now been used here to characterize a novel mutant that fails to be attracted or repelled by a variety of sensory stimuli even though it is motile

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses

Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology