Antecedent geology plays a crucial role in determining the inner-shelf, nearshore, and onshore geomorphology observed in coastal systems. However, the influence of the geologic framework on a system ...is difficult to extract when evaluating responses to changes due to storms and anthropogenic modifications, and few studies have quantified the potential for these influences in dune/beach environments. This study evaluates topographic change to the dune/beach system at Fire Island, New York over a ten year period (1998-2008) at two sites representing eastern and western reaches of the island where morphology has been shown to vary. The sites are situated along swaths of coast eroding differentially and where the inner shelf geologic framework differs substantially. Fewer large storms occurred in the first half of the study period, compared with the later part of the study period which includes several severe and prolonged extratropical storms. Additionally, a major beach replenishment project was conducted at one of the study sites. Topographic data from LiDAR and RTK GPS surveys are used to construct high-resolution 3D surfaces, which are used to determine volumetric change and to extract 2D alongshore features and profiles for analysis. The study sites help to further characterize morphologic differences between eastern and western reaches of the island. The western site displays higher sand volumes, lower dunes, and a lower gradient profile slope when compared with the eastern site. In addition to these fundamental morphologic differences, the two sites also differ significantly in their response to coastal storms and in the fact that their replenishment histories are different. The replenished areas show reduced vulnerability to storms through minimal volume loss and shoreline accretion that should be considered when evaluating the response of replenished areas to episodic events. We propose that site-specific differences evident throughout the study period can be linked to alongshore variations in the framework geology of the system. Anthropogenic modifications may have intensified differences already inherent in the system.
Summary
Background Patients with chronic hepatitis C virus and advanced fibrosis or cirrhosis are at risk for disease progression and hepatic decompensation.
Aim To determine the effects on hepatic ...histology of treatment with peginterferon alfa‐2a (90 or 180 μg/week) or interferon alfa‐2a (3 million units three times weekly) for 48 weeks in patients with paired biopsies.
Methods Liver biopsies were obtained at baseline and 6 months after end of treatment. Histological and virological responses were compared.
Results Patients attaining sustained virological response (n = 40) demonstrated the greatest improvements in fibrosis (−1.0, P < 0.0001) and inflammation (−0.65, P < 0.0001). Patients who cleared hepatitis C virus during treatment, but later relapsed (n = 59), experienced less improvement in fibrosis (−0.04, P < 0.0001) and inflammation (−0.14, P = 0.0768). Nonresponders (n = 85) showed no significant improvement in inflammation or fibrosis. Multiple regression analysis showed that the only factors contributing to improvement in fibrosis were sustained virological response (vs. nonresponder, P = 0.0005; vs. relapse, P = 0.7525) and body mass index ≤30 kg/m2 (P = 0.0995).
Conclusions These findings indicate that virological response to peginterferon alfa‐2a improves inflammation and fibrosis in hepatitis C virus patients with advanced fibrosis or cirrhosis. Improving virological response and maintaining ideal body weight are critical for achieving optimal histological outcomes in hepatitis C virus patients.
Tip‐enhanced Raman spectroscopy (TERS) is a promising technique for structural studies of biological systems and biomolecules, owing to its ability to provide a chemical fingerprint with ...sub‐diffraction‐limit spatial resolution. This application of TERS has thus far been limited, due to difficulties in generating high field enhancements while maintaining biocompatibility. The high sensitivity achievable through TERS arises from the excitation of a localized surface plasmon resonance in a noble metal atomic force microscope (AFM) tip, which in combination with a metallic surface can produce huge enhancements in the local optical field. However, metals have poor biocompatibility, potentially introducing difficulties in characterizing native structure and conformation in biomolecules, whereas biocompatible surfaces have weak optical field enhancements. Herein, a novel, biocompatible, highly enhancing surface is designed and fabricated based on few‐monolayer mica flakes, mechanically exfoliated on a metal surface. These surfaces allow the formation of coupled plasmon enhancements for TERS imaging, while maintaining the biocompatibility and atomic flatness of the mica surface for high resolution AFM. The capability of these substrates for TERS is confirmed numerically and experimentally. We demonstrate up to five orders of magnitude improvement in TERS signals over conventional mica surfaces, expanding the sensitivity of TERS to a wide range of non‐resonant biomolecules with weak Raman cross‐sections. The increase in sensitivity obtained through this approach also enables the collection of nanoscale spectra with short integration times, improving hyperspectral mapping for these applications. These mica/metal surfaces therefore have the potential to revolutionize spectromicroscopy of complex, heterogeneous biological systems such as DNA and protein complexes.
Bio‐enhancement! By combining the biocompatibility of mica surfaces with the field‐enhancement provided by metals, we have designed substrates that increase sensitivity for TERS bio‐imaging by up to five orders of magnitude.
Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies.
A retrospective study of endometrial cancer (EC) cases from 2 ...regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified.
During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04–0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18–0.80).
Universal IHC screening did not result in increased LS detection in EC.
•Significant factors associated with an abnormal IHC screen included endometrioid histology and tumor grade >1.•Significant factors associated with Lynch Syndrome were younger age and lower BMI.•Universal IHC screening did not lead to increased detection of Lynch Syndrome compared to risk-based IHC screening.•Uptake of IHC screening was inconsistent when a physician order was required.
Observed morphodynamic changes over multiple decades were coupled with storm-driven run-up characteristics at Fire Island, New York, to explore the influence of wave processes relative to the impacts ...of other coastal change drivers on the near-term evolution of the barrier island. Historical topography was generated from digital stereo-photogrammetry and compared with more recent lidar surveys to quantify near-term (decadal) morphodynamic changes to the beach and primary dune system between the years 1969, 1999, and 2009. Notably increased profile volumes were observed along the entirety of the island in 1999, and likely provide the eolian source for the steady dune crest progradation observed over the relatively quiescent decade that followed. Persistent patterns of erosion and accretion over 10-, 30-, and 40-year intervals are attributable to variations in island morphology, human activity, and variations in offshore bathymetry and island orientation that influence the wave energy reaching the coast. Areas of documented long-term historical inlet formation and extensive bayside marsh development show substantial landward translation of the dune–beach profile over the near-term period of this study. Correlations among areas predicted to overwash, observed elevation changes of the dune crestline, and observed instances of overwash in undeveloped segments of the barrier island verify that overwash locations can be accurately predicted in undeveloped segments of coast. In fact, an assessment of 2012 aerial imagery collected after Hurricane Sandy confirms that overwash occurred at the majority of near-term locations persistently predicted to overwash. In addition to the storm wave climate, factors related to variations within the geologic framework which in turn influence island orientation, offshore slope, and sediment supply impact island behavior on near-term timescales.
► Comprehensive dune-beach morphology changes are quantified over decadal intervals. ► Total water level elevations determined to assess storm influences on morphology. ► Measured changes are strongly correlated with the wave climate. ► Undeveloped areas display pronounced landward translation of the subaerial profile. ► Limited profile changes correspond with differences in along-coast influences.
Approximately 50% of patients with hepatitis C virus (HCV) genotype 1 treated with peginterferon alfa‐2a/ribavirin discontinue treatment early or experience a suboptimal response despite 48 weeks of ...therapy. The objective of this analysis was to develop a model to identify nonrapid virologic response (non‐RVR) patients who may be candidates for intensified therapy that would increase treatment response. The retrospective analysis included non‐RVR patients from four trials of 48‐week peginterferon alfa‐2a/ribavirin treatment. Patients were grouped into those who cleared virus between weeks 5 and 12 (complete early virologic responders, cEVR) or between weeks 13 and 24 (slow responders). A model was developed to predict relapse at the end of follow‐up (week 72). An optimal model was evaluated and compared with current practice by using receiver operating characteristic curves, sensitivity and specificity. In total, 539 non‐RVR patients were eligible for analysis of which 72% experienced cEVR and 28% were slow responders. Variables associated with relapse included age, ethnicity, baseline HCV RNA and interval of time to HCV RNA undetectable. The optimal model was most accurate at predicting patients at risk for relapse. The practice of considering treatment intensification (e.g. extending treatment duration) in all slow responders was less accurate but likely most practical. A week 4 HCV <2‐log reduction was the earliest but least accurate marker. We developed a model that could identify non‐RVR patients at high risk for relapse after 48 weeks of peginterferon alfa‐2a plus ribavirin and who may benefit from intensified therapy to reduce this risk of relapse.
We report the results from a haloscope search for axion dark matter in the 3.3-4.2 μeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of ..."invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.
To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations.
Women with BRCA mutations and intact ovaries were ...invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy.
A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%).
A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.
•Using a pure BRCA population, we have developed a novel Risk of Ovarian Cancer (ROCA) algorithm for HE4.•A combined CA-125 and HE4 two-marker ROCA reduces the number of false positive patient tests.•The two-marker ROCA surveillance option deserves further study to define test positive predictive value and test sensitivity
We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 ...and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months.
Women were recruited 6/13/16–9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale.
There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034).
This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.
•Compliance with biomarker blood tests performed every 4 months was high (83.2%).•Compliance with standard surveillance ultrasounds and CA 125 was significantly lower (51.9%).•Women who did biomarker testing every 4 months had lower stress scores at 12 months than at baseline.
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