Background
The growing number of cancer survivors combined with a looming shortage of oncology specialists will require greater coordination of post-treatment care responsibilities between ...oncologists and primary care physicians (PCPs). However, data are limited regarding these physicians’ views of cancer survivors’ care.
Objective
To compare PCPs and oncologists with regard to their knowledge, attitudes, and practices for follow-up care of breast and colon cancer survivors.
Design and Subjects
Mailed questionnaires were completed by a nationally representative sample of 1,072 PCPs and 1,130 medical oncologists in 2009 (cooperation rate = 65%). Sampling and non-response weights were used to calculate estimates to reflect practicing US PCPs and oncologists.
Main Measures
PCPs and oncologists reported their 1) preferred model for delivering cancer survivors’ care; 2) assessment of PCPs’ ability to perform follow-up care tasks; 3) confidence in their knowledge; and 4) cancer surveillance practices.
Key Results
Compared with PCPs, oncologists were less likely to believe PCPs had the skills to conduct appropriate testing for breast cancer recurrence (59% vs. 23%, P < 0.001) or to care for late effects of breast cancer (75% vs. 38%, P < 0.001). Only 40% of PCPs were very confident of their own knowledge of testing for recurrence. PCPs were more likely than oncologists to endorse routine use of non-recommended blood and imaging tests for detecting cancer recurrence, with both groups departing substantially from guideline recommendations.
Conclusion
There are significant differences in PCPs’ and oncologists’ knowledge, attitudes, and practices with respect to care of cancer survivors. Improving cancer survivors’ care may require more effective communication between these two groups to increase PCPs’ confidence in their knowledge, and must also address oncologists’ attitudes regarding PCPs’ ability to care for cancer survivors.
We demonstrate the fabrication of nanoperforated graphene materials with sub-20-nm features using cylinder-forming diblock copolymer templates across >1 mm2 areas. Hexagonal arrays of holes are ...etched into graphene membranes, and the remaining constrictions between holes interconnect forming a honeycomb structure. Quantum confinement, disorder, and localization effects modulate the electronic structure, opening an effective energy gap of 100 meV in the nanopatterned material. The field-effect conductivity can be modulated by 40× (200×) at room temperature (T = 105 K) as a result. A room temperature hole mobility of 1 cm2 V−1 s−1 was measured in the fabricated nanoperforated graphene field effect transistors. This scalable strategy for modulating the electronic structure of graphene is expected to facilitate applications of graphene in electronics, optoelectronics, and sensing.
While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As ...antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral “Fc fingerprint.” Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.
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•Beyond neutralization, antibodies drive antiviral control via Fc-mediated functions•Distinct vaccines elicit unique antibody Fc-effector profiles•Network analyses comprehensively integrating antibody profiles can compare vaccines•Case:control RV144 analysis points to mechanisms of reduced risk of HIV infection
Systems Serology reveals unique vaccine-induced “fingerprints,” highlighting potential markers of protection against HIV and providing a powerful method for comparing candidate vaccines against pathogens for which correlates of protection remain elusive.
For decades, chemists have strived to mimic the intricate design and diverse functions of naturally occurring systems through the bioinspired synthesis of programmable inorganic nanomaterials. The ...development of thiol-capped gold nanoparticles (AuNPs) has driven advancement in this area; however, although versatile and readily accessible, hybrid AuNPs are rarely atomically precise, which limits control over their surface topology and therefore the study of complex structure–function relationships. Here, we present a bottom-up approach to the systematic assembly of atomically precise hybrid nanoclusters employing a strategy that mimics the synthetic ease with which thiol-capped AuNPs are normally constructed, while producing well-defined covalent nanoscale assemblies with diverse surface topologies. For the first time, using a structurally characterized cluster-based organometallic building block, we demonstrate the systematic synthesis of nanoclusters with multivalent binding capabilities to complex protein targets.
A
bstract
The splitting processes of bremsstrahlung and pair production in a medium are coherent over large distances in the very high energy limit, which leads to a suppression known as the ...Landau-Pomeranchuk-Migdal (LPM) effect. In this paper, we continue analysis of the case when the coherence lengths of two consecutive splitting processes overlap (which is important for understanding corrections to standard treatments of the LPM effect in QCD), avoiding soft-gluon approximations. In particular, this paper analyzes the subtle problem of how to precisely separate overlapping double splitting (e.g. overlapping double bremsstrahlung) from the case of consecutive, independent bremsstrahlung (which is the case that would be implemented in a Monte Carlo simulation based solely on single splitting rates). As an example of the method, we consider the rate of real double gluon bremsstrahlung from an initial gluon with various simplifying assumptions (thick media;
q
approximation; large
N
c
; and neglect for the moment of processes involving 4-gluon ver-tices) and explicitly compute the correction Δ
d
Γ
/dx dy
due to overlapping formation times.
Mesenchymal stromal cells (MSCs) tend to infiltrate into tumors and form a major component of the tumor microenvironment. These tumor-resident MSCs are known to affect tumor growth, but the ...mechanisms are largely unknown. We found that MSCs isolated from spontaneous lymphomas in mouse (L-MSCs) strikingly enhanced tumor growth in comparison to bone marrow MSCs (BM-MSCs). L-MSCs contributed to greater recruitment of CD11b+Ly6C+ monocytes, F4/80+ macrophages, and CD11b+Ly6G+ neutrophils to the tumor. Depletion of monocytes/macrophages, but not neutrophils, completely abolished tumor promotion of L-MSCs. Furthermore, L-MSCs expressed high levels of CCR2 ligands, and monocyte/macrophage accumulation and L-MSC-mediated tumor promotion were largely abolished in CCR2−/− mice. Intriguingly, TNFα-pretreated BM-MSCs mimicked L-MSCs in their chemokine production profile and ability to promote tumorigenesis of lymphoma, melanoma, and breast carcinoma. Therefore, our findings demonstrate that, in an inflammatory environment, tumor-resident MSCs promote tumor growth by recruiting monocytes/macrophages.
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► Tumor-resident MSCs promote tumor growth more potently than normal tissue MSCs ► Tumor-resident MSCs recruit monocytes/macrophages that are crucial for tumor growth ► Tumor-resident MSCs produce abundant CCR2 ligands for monocyte/macrophage trafficking ► TNFα-pretreated BM-MSCs enhance tumor progression similarly to tumor-derived MSCs
Mesenchymal stromal cells infiltrating tumors are educated by local TNF-alpha to produce CCR2 ligands. As a result, monocytes/macrophages are recruited to the tumor mass, which in turn promotes tumor growth.
The tumour-suppressor phosphatase with tensin homology (PTEN) is the most important negative regulator of the cell-survival signalling pathway initiated by phosphatidylinositol 3-kinase (PI3K). ...Although PTEN is mutated or deleted in many tumours, deregulation of the PI3K-PTEN network also occurs through other mechanisms. Crosstalk between the PI3K pathways and other tumorigenic signalling pathways, such as those that involve Ras, p53, TOR (target of rapamycin) or DJ1, can contribute to this deregulation. How does the PI3K pathway integrate signals from numerous sources, and how can this information be used in the rational design of cancer therapies?
Progressive synaptic degeneration and neuron loss are major structural correlates of cognitive impairment in Alzheimer's disease (AD). The mechanisms by which synaptic degeneration in AD occurs have ...not been established. The activation of proteins within the caspase family has been implicated in AD-associated neurodegeneration, and synaptically localized caspase activity could play a role in the synaptic degeneration and loss found in AD. We used synaptosomal fractionation with Western blotting and immunohistochemistry to examine the anatomical, subcellular, and subsynaptic expression patterns of caspase 3 in both the anterior cingulate cortex and hippocampus of control and AD patients. In both control and AD cases, there was a selective enrichment of caspase- 3 at synapses, particularly in the postsynaptic density (PSD) fractions. Compared with controls, AD patients exhibited significant increases in synaptic procaspase- 3 and active caspase-3 expression levels that were most evident in the PSD fractions. These data demonstrate for the first time the preferential localization and increase of caspase-3 in the PSD fractions in AD and suggest an important role for caspase 3 in synapse degeneration during disease progression.
While a potential causal factor in Alzheimer's disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the ...hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway. Reduced insulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS⁶¹⁶) and IRS-1 pS⁶³⁶/⁶³⁹. In the HF, these candidate biomarkers of brain insulin resistance increased commonly and progressively from normal cases to mild cognitively impaired cases to AD cases regardless of diabetes or APOE ε4 status. Levels of IRS-1 pS⁶¹⁶ and IRS-1 pS⁶³⁶/⁶³⁹ and their activated kinases correlated positively with those of oligomeric Aβ plaques and were negatively associated with episodic and working memory, even after adjusting for Aβ plaques, neurofibrillary tangles, and APOE ε4. Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβ oligomers and yet promoting cognitive decline independent of classic AD pathology.
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