2,826 research outputs found
Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer.
Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC
Interventions to promote cost-effectiveness in adult Intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study
Background
There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources.
Methods
A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as ‘critical’ by more than 50% of steering committee members. These interventions and experts’ comments were summarized as final considerations for best practice.
Results
At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 ‘critical’ best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept.
Conclusions
This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources
Electronic Devices Based on Purified Carbon Nanotubes Grown By High Pressure Decomposition of Carbon Monoxide
The excellent properties of transistors, wires, and sensors made from
single-walled carbon nanotubes (SWNTs) make them promising candidates for use
in advanced nanoelectronic systems. Gas-phase growth procedures such as the
high pressure decomposition of carbon monoxide (HiPCO) method yield large
quantities of small diameter semiconducting SWNTs, which are ideal for use in
nanoelectronic circuits. As-grown HiPCO material, however, commonly contains a
large fraction of carbonaceous impurities that degrade properties of SWNT
devices. Here we demonstrate a purification, deposition, and fabrication
process that yields devices consisting of metallic and semiconducting nanotubes
with electronic characteristics vastly superior to those of circuits made from
raw HiPCO. Source-drain current measurements on the circuits as a function of
temperature and backgate voltage are used to quantify the energy gap of
semiconducting nanotubes in a field effect transistor geometry. This work
demonstrates significant progress towards the goal of producing complex
integrated circuits from bulk-grown SWNT material.Comment: 6 pages, 4 figures, to appear in Nature Material
Spatially Resolved Magnetic Field Structure in the Disk of a T Tauri Star
Magnetic fields in accretion disks play a dominant role during the star
formation process but have hitherto been observationally poorly constrained.
Field strengths have been inferred on T Tauri stars themselves and possibly in
the innermost part of the accretion disk, but the strength and morphology of
the field in the bulk of the disk have not been observed. Unresolved
measurements of polarized emission (arising from elongated dust grains aligned
perpendicular to the field) imply average fields aligned with the disks.
Theoretically, the fields are expected to be largely toroidal, poloidal, or a
mixture of the two, which imply different mechanisms for transporting angular
momentum in the disks of actively accreting young stars such as HL Tau. Here we
report resolved measurements of the polarized 1.25 mm continuum emission from
HL Tau's disk. The magnetic field on a scale of 80 AU is coincident with the
major axis (~210 AU diameter) of the disk. From this we conclude that the
magnetic field inside the disk at this scale cannot be dominated by a vertical
component, though a purely toroidal field does not fit the data well either.
The unexpected morphology suggests that the magnetic field's role for the
accretion of a T Tauri star is more complex than the current theoretical
understanding.Comment: Accepted for publication in Natur
Intramedullary knee spacer in 2-stage revision knee surgery with segmental bone loss: A technical note involving 6 cases
The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder
In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844),
Goldbeter and Koshland mathematically analyzed a reversible covalent
modification system which is highly sensitive to the concentration of
effectors. Its signal-response curve appears sigmoidal, constituting a
biochemical switch. However, the switch behavior only emerges in the
"zero-order region", i.e. when the signal molecule concentration is much lower
than that of the substrate it modifies. In this work we showed that the
switching behavior can also occur under comparable concentrations of signals
and substrates, provided that the signal molecules catalyze the modification
reaction in cooperation. We also studied the effect of dynamic disorders on the
proposed biochemical switch, in which the enzymatic reaction rates, instead of
constant, appear as stochastic functions of time. We showed that the system is
robust to dynamic disorder at bulk concentration. But if the dynamic disorder
is quasi-static, large fluctuations of the switch response behavior may be
observed at low concentrations. Such fluctuation is relevant to many biological
functions. It can be reduced by either increasing the conformation
interconversion rate of the protein, or correlating the enzymatic reaction
rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON
Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat
Seatbelt use and risk of major injuries sustained by vehicle occupants during motor-vehicle crashes: A systematic review and meta-analysis of cohort studies
BackgroundIn 2004, a World Health Report on road safety called for enforcement of measures such as seatbelt use, effective at minimizing morbidity and mortality caused by road traffic accidents. However, injuries caused by seatbelt use have also been described. Over a decade after publication of the World Health Report on road safety, this study sought to investigate the relationship between seatbelt use and major injuries in belted compared to unbelted passengers.MethodsCohort studies published in English language from 2005 to 2018 were retrieved from seven databases. Critical appraisal of studies was carried out using the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Pooled risk of major injuries was assessed using the random effects meta-analytic model. Heterogeneity was quantified using I-squared and Tau-squared statistics. Funnel plots and Egger's test were used to investigate publication bias. This review is registered in PROSPERO (CRD42015020309).ResultsEleven studies, all carried out in developed countries were included. Overall, the risk of any major injury was significantly lower in belted passengers compared to unbelted passengers (RR 0.47; 95%CI, 0.29 to 0.80; I-2=99.7; P=0.000). When analysed by crash types, belt use significantly reduced the risk of any injury (RR 0.35; 95%CI, 0.24 to 0.52). Seatbelt use reduces the risk of facial injuries (RR=0.56, 95% CI=0.37 to 0.84), abdominal injuries (RR=0.87; 95% CI=0.78 to 0.98) and, spinal injuries (RR=0.56, 95% CI=0.37 to 0.84). However, we found no statistically significant difference in risk of head injuries (RR=0.49; 95% CI=0.22 to 1.08), neck injuries (RR=0.69: 95%CI 0.07 to 6.44), thoracic injuries (RR 0.96, 95%CI, 0.74 to 1.24), upper limb injuries (RR=1.05, 95%CI 0.83 to 1.34) and lower limb injuries (RR=0.77, 95%CI 0.58 to 1.04) between belted and non-belted passengers.ConclusionIn sum, the risk of most major road traffic injuries is lower in seatbelt users. Findings were inconclusive regarding seatbelt use and susceptibility to thoracic, head and neck injuries during road traffic accidents. Awareness should be raised about the dangers of inadequate seatbelt use. Future research should aim to assess the effects of seatbelt use on major injuries by crash type
CRYSTAL-FIELD EFFECTS IN THE ELECTRON-SPIN-RESONANCE OF GD3+ AND ER3+ IN PR2CUO4
The low-temperature (T < 300 K) electron-spin-resonance (ESR) spectra of Gd3+ and Er3+ in Pr2CuO4 show symmetry properties appropriate to the crystal tetragonal symmetry. The completely resolved Gd3+ spectra allowed us to measure, at T = 2 K, the principal g values g parallel-to = 1.985(8), g perpendicular-to =2.040(8), and the crystal-field parameters [b2(0) = -399(2) X 10(-4) cm-1, b4(0) = -33.1(7) X 10(-4) cm-1, and b4(4) = 205(3) X 10(-4) cm-1]. The large broadening of the ESR lines, observed above T approximately 40 K, is due to a relaxation via the thermally populated crystal-field excited Pr levels. For Er3+ in Pr2CuO4 we observe a single ESR line corresponding to a ground-state doublet with g parallel-to = 17.94(5) and g perpendicular-to less-than-or-equal-to 0.2. The absence of any splittings of the ESR lines below the Neel temperature implies that the magnetostatic dipole field at the rare-earth-ion site due to the antiferromagnetically ordered Cu moments is < 45 Oe.44282682
The Surgical Infection Society revised guidelines on the management of intra-abdominal infection
Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations.
Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council.
Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included.
Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline
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