Fault Slip and Exhumation History of the Willard Thrust Sheet, Sevier Fold‐Thrust Belt, Utah: Relations to Wedge Propagation, Hinterland Uplift, and Foreland Basin Sedimentation

Zircon (U‐Th)/He (ZHe) and zircon fission track thermochronometric data for 47 samples spanning the areally extensive Willard thrust sheet within the western part of the Sevier fold‐thrust belt record enhanced cooling and exhumation during major thrust slip spanning approximately 125–90 Ma. ZHe and zircon fission track age‐paleodepth patterns along structural transects and age‐distance relations along stratigraphic‐parallel traverses, combined with thermo‐kinematic modeling, constrain the fault slip history, with estimated slip rates of ~1 km/Myr from 125 to 105 Ma, increasing to ~3 km/Myr from 105 to 92 Ma, and then decreasing as major slip was transferred onto eastern thrusts. Exhumation was concentrated during motion up thrust ramps with estimated erosion rates of ~0.1 to 0.3 km/Myr. Local cooling ages of approximately 160–150 Ma may record a period of regional erosion, or alternatively an early phase of limited... (see full abstract in article)

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

End-Stage Renal Disease Among HIV-Infected Adults in North America

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Rip current observations on a low-sloping dissipative beach

Rip currents are the main cause of beach rescues and fatalities. Key drivers of rip current hazard are: (1) fast current speeds; and (2) the exit rate of floating material from inside to outside of the surf zone. Exit rates may vary temporally, such as due to Very Low Frequency (VLF) motions, which have a period on the order of 10 minutes. However, there is little field data to determine the driver(s) of exit rate. Therefore, the aim of this research was to determine rip current circulation patterns, and specifically, determine their relationship to surf zone exits, on a high-energy dissipative beach. Three days of field measurements were undertaken at Ngarunui Beach, New Zealand. Three daily surf zone flow patterns were found: (1) alongshore; (2) surf zone eddy with high exit rate; and (3) surf zone eddy with no exits. There were strong infragravity peaks in energy within the surf zone, at 30-45s, although none at VLF (~10 minute) frequencies. Further research is underway to determine what drove the high surf zone exit rate observed at Ngarunui Beach

Storm-driven changes in rip channel patterns on an embayed beach

This paper introduces a semi-automatic computer algorithm designed to detect rip current channels in video imagery. As a case study, this method is applied to 3.3 years of video data from an embayed beach to demonstrate the link between antecedent surf zone morphology, wave energy and up/down transitions in beach state. An objective measure of rip channel change was developed to define six significant rip reconfiguration events and relate these events to wave energy. Over the period of study no complete resets of the nearshore morphology occurred. The analysis indicates that direct correlation of rip patterns with the instantaneous wave conditions is not a useful way to demonstrate how rips and waves interact. The average wave energy over a period of ten days, combined with storm duration were good indicators of rip channel change, demonstrating that in general, beach morphology responds with a time lag to changes in forcing. Rip channels with a short cross-shore length and narrow alongshore spacing responded faster to changes in wave conditions than rips with a long cross-shore length and wider alongshore spacing. To force changes in the rip morphology, longer rip channels required wave events of higher energy and/or a longer duration. Offshore islands protect the beach under certain wave approach angles, sometimes resulting in a dual-width surf zone, which was narrow at the sheltered end and wide at the exposed end of the beach. The wider surf zone end was characterised by three dominant and persistent rip channels, whereas the narrow surf zone section contained a number of smaller rips which evolved rapidly under wave forcing. Our observations demonstrate the importance of rip channel size in controlling the response time of nearshore morphology

Pulsations in surf zone currents on a high energy mesotidal beach in New Zealand

The exchange of material between the surf zone and continental shelf can be driven by pulsations in rip current velocities. However, there is a poor understanding of the relationship of these pulsations to surf zone morphology and material exchange. Moreover, understanding of rip current dynamics has focused mainly on single-barred beaches in an intermediate state, and there have been few studies on high energy beaches. Therefore, this paper undertakes preliminary research on surf zone current velocity pulsations, on a high energy beach in New Zealand. This initial analysis presents results from two days of measurements using Acoustic Doppler Velocimeters and Lagrangian GPS drifters. Drifters revealed pulsations in current velocities on the order of ~0.5-2 m s⁻¹ throughout the surf zone, whether inside a rip current circulation cell or not. More infragravity wave energy was associated with constant pulsations in current velocity, and lower infragravity energy with pulsation bursts, lasting 5-10 minutes, interspersed with periods of relatively constant velocity lasting 15-25 minutes. However, higher wave conditions also reduced the exit rate from the surf zone.5 page(s