Introduction Direct-to-consumer m Health devices are a potential asset to behavioral research but rarely tested as intervention tools. This trial examined the accelerometer-based Fitbit tracker and ...website as a low-touch physical activity intervention. The purpose of this study is to evaluate, within an RCT, the feasibility and preliminary efficacy of integrating the Fitbit tracker and website into a physical activity intervention for postmenopausal women. Methods Fifty-one inactive, postmenopausal women with BMI ≥25.0 were randomized to a 16-week web-based self-monitoring intervention ( n =25) or comparison group ( n =26). The Web-Based Tracking Group received a Fitbit, instructional session, and follow-up call at 4 weeks. The comparison group received a standard pedometer. All were asked to perform 150 minutes/week of moderate to vigorous physical activity (MVPA). Physical activity outcomes were measured by the ActiGraph GT3X+ accelerometer. Results Data were collected and analyzed in 2013–2014. Participants were aged 60 (SD=7) years with BMI of 29.2 (3.5) kg/m2 . Relative to baseline, the Web-Based Tracking Group increased MVPA by 62 (108) minutes/week ( p <0.01); 10-minute MVPA bouts by 38 (83) minutes/week ( p =0.008); and steps by 789 (1,979) ( p =0.01), compared to non-significant increases in the Pedometer Group (between-group p =0.11, 0.28, and 0.30, respectively). The Web-Based Tracking Group wore the tracker on 95% of intervention days; 96% reported liking the website and 100% liked the tracker. Conclusions The Fitbit was well accepted in this sample of women and associated with increased physical activity at 16 weeks. Leveraging direct-to-consumer m Health technologies aligned with behavior change theories can strengthen physical activity interventions.
Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have ...received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges.
In order to gain a more comprehensive insight into the nature of venetoclax resistance mechanisms, we evaluated the changes in the BCL-2 family members at the genetic and expression levels in seven different venetoclax-resistant derived leukemia and lymphoma cell lines.
Gene and protein expression analyses identified a number of different alterations in the expression of pro- and anti-apoptotic BCL-2 family members. In the resistant derived cells, an increase in either or both the anti-apoptotic proteins BCL-X
or MCL-1, which are not targeted by venetoclax was observed, and either concomitant or exclusive with a decrease in one or more pro-apoptotic proteins. In addition, mutational analysis also revealed a mutation in the BH3 binding groove (F104L) that could potentially interfere with venetoclax-binding. Not all changes may be causally related to venetoclax resistance and may only be an epiphenomenon. For resistant cell lines showing elevations in BCL-X
or MCL-1, strong synergistic cell killing was observed when venetoclax was combined with either BCL-X
- or MCL-1-selective inhibitors, respectively. This highlights the importance of BCL-X
- and MCL-1 as causally contributing to venetoclax resistance.
Overall our study identified numerous changes in multiple resistant lines; the changes were neither mutually exclusive nor universal across the cell lines tested, thus exemplifying the complexity and heterogeneity of potential resistance mechanisms. Identifying and evaluating their contribution has important implications for both patient selection and the rational development of strategies to overcome resistance.
The DSM-5 Personality and Personality Disorders Work Group formulated a hybrid dimensional/categorical model that represented personality disorders as combinations of core impairments in personality ...functioning with specific configurations of problematic personality traits. Specific clusters of traits were selected to serve as indicators for six DSM categorical diagnoses to be retained in this system - antisocial, avoidant, borderline, narcissistic, obsessive-compulsive and schizotypal personality disorders. The goal of the current study was to describe the empirical relationships between the DSM-5 section III pathological traits and DSM-IV/DSM-5 section II personality disorder diagnoses.
Data were obtained from a sample of 337 clinicians, each of whom rated one of his or her patients on all aspects of the DSM-IV and DSM-5 proposed alternative model. Regression models were constructed to examine trait-disorder relationships, and the incremental validity of core personality dysfunctions (i.e. criterion A features for each disorder) was examined in combination with the specified trait clusters.
Findings suggested that the trait assignments specified by the Work Group tended to be substantially associated with corresponding DSM-IV concepts, and the criterion A features provided additional diagnostic information in all but one instance.
Although the DSM-5 section III alternative model provided a substantially different taxonomic structure for personality disorders, the associations between this new approach and the traditional personality disorder concepts in DSM-5 section II make it possible to render traditional personality disorder concepts using alternative model traits in combination with core impairments in personality functioning.
The Loop Current System, involving the Loop Current and Loop Current Eddies, is the principal circulation feature in the Gulf of Mexico, which exhibits salinity gradients due to Mississippi River ...system freshwater discharge and large salinity variability on seasonal timescales. This research uses satellite‐derived sea surface salinity from NASA's Soil Moisture Active Passive and ESA's Soil Moisture and Ocean Salinity missions with altimetric sea surface height data to observe and quantify the redistribution of low‐salinity water by Loop Current System interaction. Freshwater flux in this region during summer months is modulated by Loop Current System configuration as classified by three states. An extended Loop Current transports low‐salinity water southward to the Florida Straits. A Loop Current eddy near the Louisiana‐Texas shelf recirculates low‐salinity water within the central Gulf. During a retracted Loop Current, no interaction occurs and low‐salinity water remains close to the coast in the northern Gulf.
Plain Language Summary
The Gulf of Mexico receives freshwater from the Mississippi and Atchafalaya Rivers with an annual peak during spring due to snow melt over the upper part of the watershed. The fresh water forms a low‐salinity water plume, which evolves based on local wind forcing as well as circulation features associated with the Loop Current System. The Loop Current brings Caribbean Sea water northward into the Gulf of Mexico and transports waters out of the Gulf through the Florida Straits where it feeds into the Gulf Stream. While inside the Gulf, the Loop Current can extend northward to the Mississippi‐Alabama coast. When extended northward, the Loop Current advects low‐salinity water eastward along the Mississippi/Alabama/Florida shelf, and southward along the West Florida Shelf. This low‐salinity water then exits the Gulf through the Florida Straits. Additionally, the Loop Current occasionally sheds anticyclonic eddies which migrate westward to the Texas coast, and can recirculate low‐salinity water in the central Gulf of Mexico. Analysis of nearly a decade of satellite salinity data shows a preference for events of freshwater flux toward the southeastern Gulf of Mexico during the late summer months with substantial interannual variability linked with the configuration of the Loop Current System.
Key Points
Utilization of satellite‐derived surface salinity to study freshwater fluxes and salinity variability in the Gulf of Mexico is presented
Loop Current System configuration, not river discharge, determines patterns of lateral freshwater fluxes and surface salinity signatures
Loop Current System configurations are classified as favorable or not for strong freshwater flux during summer months
Zooplankton play an important role in global biogeochemistry, and their
secondary production supports valuable fisheries of the world's oceans.
Currently, zooplankton standing stocks cannot be ...estimated using remote
sensing techniques. Hence, coupled physical–biogeochemical models (PBMs)
provide an important tool for studying zooplankton on regional and global
scales. However, evaluating the accuracy of zooplankton biomass estimates
from PBMs has been a major challenge due to sparse observations. In this
study, we configure a PBM for the Gulf of Mexico (GoM) from 1993 to 2012 and
validate the model against an extensive combination of biomass and rate
measurements. Spatial variability in a multidecadal database of
mesozooplankton biomass for the northern GoM is well resolved by the model
with a statistically significant (p < 0.01) correlation of 0.90.
Mesozooplankton secondary production for the region averaged 66±8×109 kg C yr−1, equivalent to ∼10 % of
net primary production (NPP), and ranged from 51 to 82×109 kg C yr−1, with higher secondary production inside cyclonic eddies and
substantially reduced secondary production in anticyclonic eddies. Model
results from the shelf regions suggest that herbivory is the dominant
feeding mode for small mesozooplankton (< 1 mm), whereas larger mesozooplankton are primarily carnivorous. In open-ocean oligotrophic
waters, however, both mesozooplankton groups show proportionally greater
reliance on heterotrophic protists as a food source. This highlights an
important role of microbial and protistan food webs in sustaining
mesozooplankton biomass in the GoM, which serves as the primary food source
for early life stages of many commercially important fish species, including
tuna.
Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the ...latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X(L) inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.
Detection of oil floating on the ocean surface, and particularly thick layers of it, is crucial for emergency response to oil spills. While detection of oil on the ocean surface is possible under ...moderate sea-state conditions using a variety of remote-sensing methods, estimation of oil layer thickness is technically challenging. In this paper, we used synthetic aperture radar (SAR) imagery collected during the Deepwater Horizon oil spill and the Texture Classifier Neural Network Algorithm (TCNNA) to identify the spill's extent. We then developed an oil emulsion detection algorithm using TCNNA outputs to enhance the contrast of pixels within the oil slick in order to identify SAR image signatures that may correspond to regions of thick, emulsified oil. These locations were found to be largely consistent with ship-based observations and optical and thermal remote-sensing instrument data. The detection method identifies regions of increased radar backscattering within larger areas of oilcovered water. Detection was dependent on SAR incident angles and SAR beam mode configuration. L-band SAR was found to have the largest window of incidence angles (19–38° off nadir) useful for detecting oil emulsions. C-band SAR showed a narrower window (20–32° off nadir) than L-band, while X-band SAR had the narrowest window (20–31° off nadir). The results suggest that in case of future spills in the ocean, SAR data may be used to identify oil emulsions to help make management decisions.
To determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost.
Four hundred ...ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer.
Median follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer-specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer-specific death (P = .0482), but not for IBTR (P = .346).
The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.
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