Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of ...resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
The hippocampal formation and striatum subserve declarative and procedural memory, respectively. However, experimental evidence suggests that the ventral striatum, as opposed to the dorsal striatum, ...does not lend itself to being part of either system. Instead, it may constitute a system integrating inputs from the amygdala, prefrontal cortex and hippocampus to generate motivational, outcome-predicting signals that invigorate goal-directed behaviors. Inspired by reinforcement learning models, we suggest an alternative scheme for computational functions of the striatum. Dorsal and ventral striatum are proposed to compute outcome predictions largely in parallel, using different types of information as input. The nature of the inputs to striatum is furthermore combinatorial, and the specificity of predictions transcends the level of scalar value signals, incorporating episodic information.
The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined ...by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium‐sulphur colloid (99mTc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag®, which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non‐inferiority of SentiMag® vs. 99mTc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99mTc and SentiMag® was 97.9%. The DR per patient was 99.0% for 99mTc and 97.9% for SentiMag®. SentiMag® appears to be non‐inferior to the radiotracer and safe. While 99mTc remains the standard, SentiMag® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+® allows effective treatment of breast cancer patients.
Polyamines are small cationic molecules required for cellular proliferation and are detected at higher concentrations in most tumour tissues, compared to normal tissues. Agmatine (AGM), a biogenic ...amine, is able to arrest proliferation in cell lines by depleting intracellular polyamine levels. It enters mammalian cells via the polyamine transport system. Agmatine is able to induce oxidative stress in mitochondria at low concentrations (10 or 100 μM), while at higher concentrations (e.g. 1–2 mM) it does not affect mitochondrial respiration and is ineffective in inducing any oxidative stress. As this effect is strictly correlated with the mitochondrial permeability transition induction and the triggering of the pro-apoptotic pathway, AGM may be considered as a regulator of this type of cell death. Furthermore, polyamine transport is positively correlated with the rate of cellular proliferation. By increasing the expression of antizyme, a protein that inhibits polyamine biosynthesis and transport, AGM also exhibits a regulatory effect on cell proliferation. Methylglyoxal
bis
(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosyl-
l
-methionine decarboxylase, displaying anticancer activity, is a structural analogue of the natural polyamine spermidine. MGBG has been extensively studied, preclinically as well as clinically, and its anticancer activity has been attributed to the inhibition of polyamine biosynthesis and also to its effect on mitochondrial function. Numerous findings have suggested that MGBG might be used as a chemotherapeutic agent against cancer.
Valid and reliable public health data are becoming more difficult to obtain through random-digit dial (RDD) telephone surveys. As a result, researchers are evaluating different survey designs (i.e., ...sampling frame and survey mode combinations) as complements or alternatives to RDD. Traditionally, mail surveys of the general public have been limited due to a lack of a complete sampling frame of households. Recent advances in electronic record keeping, however, have allowed researchers to develop a sample from a frame of addresses (e.g., the U.S. Postal Service Delivery Sequence File, which appears to provide coverage which rivals or possibly exceeds that obtained through RDD sampling methods). To test the use of this frame for surveying adults aged 18 years and older across a wide geographic area, a pilot study was conducted as part of the 2005 Behavioral Risk Factor Surveillance System (BRFSS). The pilot compared use of a traditional, RDD telephone survey methodology to an approach using a mail version of the questionnaire completed by a random sample of households drawn from an address-based frame. The findings indicate that the mail survey approach can achieve higher response rates in low-response-rate states (<40%) than RDD (particularly when two mailings are sent). Additionally, the address frame with mail survey design provides access to cell phone only households and offers cost savings over the telephone approach. The resulting sample, however, significantly overrepresents non-Hispanic whites and people with higher levels of education.
Regulatory T cell (Treg)-mediated immunosuppression is considered a major obstacle for successful cancer immunotherapy. The association between clinical outcome and Tregs is being studied extensively ...in clinical trials, but unfortunately, no consensus has been reached about (a) the markers and (b) the gating strategy required to define human Tregs in this context, making it difficult to draw final conclusions. Therefore, we have organized an international workshop on the detection and functional testing of Tregs with leading experts in the field, and 40 participants discussing different analyses and the importance of different markers and context in which Tregs were analyzed. This resulted in a rationally composed ranking list of “Treg markers”. Subsequently, the proposed Treg markers were tested to get insight into the overlap/differences between the most frequently used Treg definitions and their utility for Treg detection in various human tissues. Here, we conclude that the CD3, CD4, CD25, CD127, and FoxP3 markers are the minimally required markers to define human Treg cells. Staining for Ki67 and CD45RA showed to provide additional information on the activation status of Tregs. The use of markers was validated in a series of PBMC from healthy donors and cancer patients, as well as in tumor-draining lymph nodes and freshly isolated tumors. In conclusion, we propose an essential marker set comprising antibodies to CD3, CD4, CD25, CD127, Foxp3, Ki67, and CD45RA and a corresponding robust gating strategy for the context-dependent analysis of Tregs by flow cytometry.
To date, the effects of long-term testosterone (T) administration on the human vagina are not completely understood. Thus, the aim of this study was to investigate the effects of long-term T ...treatment on vaginal tissue histology, estrogen receptor alpha (ERα) and beta (ERβ) expression and proliferation in female to male transsexual subjects (FtM). We compared vaginal samples from FtM subjects with those of premenopausal women (PrM) and postmenopausal women (M) not receiving any hormonal treatment for at least 2 years. Vaginal tissue samples from 16 FtM subjects treated with T (intramuscular injections of 100 mg Testoviron Depot/7-10 days for at least 1 year), undergoing sex reassignment surgery, and 16 PrM and 16 M subjects undergoing a vaginal hysterectomy for prolapse, were collected. For each sample, morphology, glycogen content, proliferation (ki-67), ERα and ERβ expression were evaluated. Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted. T administration resulted in a strong proliferation reduction when compared with both M and PrM subjects. Stromal and epithelial ERα as well as ERβ were significantly decreased in FtM when compared with PrM subjects. In conclusion, our data suggests that systemic T administration at supraphysiological dosage, determines profound changes in histomorphology and reduces ERs expression and proliferation of vaginal epithelium.
In this paper we present the Low Frequency Instrument (LFI), designed and developed as part of the Planck space mission, the ESA programme dedicated to precision imaging of the cosmic microwave ...background (CMB). Planck-LFI will observe the full sky in intensity and polarisation in three frequency bands centred at 30, 44 and 70 GHz, while higher frequencies (100–850 GHz) will be covered by the HFI instrument. The LFI is an array of microwave radiometers based on state-of-the-art indium phosphide cryogenic HEMT amplifiers implemented in a differential system using blackbody loads as reference signals. The front end is cooled to 20 K for optimal sensitivity and the reference loads are cooled to 4 K to minimise low-frequency noise. We provide an overview of the LFI, discuss the leading scientific requirements, and describe the design solutions adopted for the various hardware subsystems. The main drivers of the radiometric, optical, and thermal design are discussed, including the stringent requirements on sensitivity, stability, and rejection of systematic effects. Further details on the key instrument units and the results of ground calibration are provided in a set of companion papers.
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