Accounting for changing temperature patterns increases historical estimates of climate sensitivity

Eight atmospheric general circulation models (AGCMs) are forced with observed historical (1871–2010) monthly sea surface temperature and sea ice variations using the Atmospheric Model Intercomparison Project II data set. The AGCMs therefore have a similar temperature pattern and trend to that of observed historical climate change. The AGCMs simulate a spread in climate feedback similar to that seen in coupled simulations of the response to CO2 quadrupling. However, the feedbacks are robustly more stabilizing and the effective climate sensitivity (EffCS) smaller. This is due to a pattern effect, whereby the pattern of observed historical sea surface temperature change gives rise to more negative cloud and longwave clear‐sky feedbacks. Assuming the patterns of long‐term temperature change simulated by models, and the radiative response to them, are credible; this implies that existing constraints on EffCS from historical energy budget variations give values that are too low and overly constrained, particularly at the upper end. For example, the pattern effect increases the long‐term Otto et al. (2013, https://doi.org/10.1038/ngeo1836) EffCS median and 5–95% confidence interval from 1.9 K (0.9–5.0 K) to 3.2 K (1.5–8.1 K

Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1

Achieving the vision of identifying and quantifying cancer-related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion. Delineated here are the design and evaluation of a newly synthesized turn-on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins. Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone-based enzyme substrate. Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two-electron reduction of the sterically and conformationally restricted quinone substrate by the cancer-associated human NAD(P)H:quinone oxidoreductase isozyme 1 (hNQO1). Successes of the approach include rapid differentiation of NQO1-expressing and -nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two-photon microscopy. The potential for use of the turn-on probe in longer-term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability. © 2012 American Chemical Society

Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α(2)-adrenergic receptor (α(2)-AR) density in adolescent (35-days-old) rats, using [(3)H]RX821002 (5 nM). RESULTS: Sex-specific alterations of α(2)-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α(2)-AR in parietal cortex. CONCLUSION: These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine

Patient-Facing Mobile Apps to Treat High-Need, High-Cost Populations: A Scoping Review

BACKGROUND: Self-management is essential to caring for high-need, high-cost (HNHC) populations. Advances in mobile phone technology coupled with increased availability and adoption of health-focused mobile apps have made self-management more achievable, but the extent and quality of the literature supporting their use is not well defined. OBJECTIVE: The purpose of this review was to assess the breadth, quality, bias, and types of outcomes measured in the literature supporting the use of apps targeting HNHC populations. METHODS: Data sources included articles in PubMed and MEDLINE (National Center for Biotechnology Information), EMBASE (Elsevier), the Cochrane Central Register of Controlled Trials (EBSCO), Web of Science (Thomson Reuters), and the NTIS (National Technical Information Service) Bibliographic Database (EBSCO) published since 2008. We selected studies involving use of patient-facing iOS or Android mobile health apps. Extraction was performed by 1 reviewer; 40 randomly selected articles were evaluated by 2 reviewers to assess agreement. RESULTS: Our final analysis included 175 studies. The populations most commonly targeted by apps included patients with obesity, physical handicaps, diabetes, older age, and dementia. Only 30.3% (53/175) of the apps studied in the reviewed literature were identifiable and available to the public through app stores. Many of the studies were cross-sectional analyses (42.9%, 75/175), small (median number of participants=31, interquartile range 11.0-207.2, maximum 11,690), or performed by an app\u27s developers (61.1%, 107/175). Of the 175 studies, only 36 (20.6%, 36/175) studies evaluated a clinical outcome. CONCLUSIONS: Most apps described in the literature could not be located on the iOS or Android app stores, and existing research does not robustly evaluate the potential of mobile apps. Whereas apps may be useful in patients with chronic conditions, data do not support this yet. Although we had 2-3 reviewers to screen and assess abstract eligibility, only 1 reviewer abstracted the data. This is one limitation of our study. With respect to the 40 articles (22.9%, 40/175) that were assigned to 2 reviewers (of which 3 articles were excluded), inter-rater agreement was significant on the majority of items (17 of 30) but fair-to-moderate on others

“What if There's Something Wrong with Her?”‐How Biomedical Technologies Contribute to Epistemic Injustice in Healthcare

While there is a steadily growing literature on epistemic injustice in healthcare, there are few discussions of the role that biomedical technologies play in harming patients in their capacity as knowers. Through an analysis of newborn and pediatric genetic and genomic sequencing technologies (GSTs), I argue that biomedical technologies can lead to epistemic injustice through two primary pathways: epistemic capture and value partitioning. I close by discussing the larger ethical and political context of critical analyses of GSTs and their broader implications for just and equitable healthcare delivery

Anterior Cruciate Ligament Rehabilitation for the 10- to 18-Year-Old Adolescent Athlete:Practice Guidelines Based on International Delphi Consensus

Background:There are 2 treatment options for adolescent athletes with anterior cruciate ligament (ACL) injuries—rehabilitation alone (nonsurgical treatment) or ACL reconstruction plus rehabilitation. However, there is no clear consensus on how to include strength and neuromuscular training during each phase of rehabilitation.Purpose:To develop a practical consensus for adolescent ACL rehabilitation to help provide care to this age group using an international Delphi panel.Study Design:Consensus statement.Methods:A 3-round online international Delphi consensus study was conducted. A mix of open and closed literature-based statements were formulated and sent out to an international panel of 20 ACL rehabilitation experts. Statements were divided into 3 domains as follows: (1) nonsurgical rehabilitation; (2) prehabilitation; and (3) postoperative rehabilitation. Consensus was defined as 70% agreement between panel members.Results:Panel members agreed that rehabilitation should consist of 3 criterion-based phases, with continued injury prevention serving as a fourth phase. They also reached a consensus on rehabilitation being different for 10- to 16-year-olds compared with 17- and 18-year-olds, with a need to distinguish between prepubertal (Tanner stage 1) and mid- to postpubertal (Tanner stages 2-5) athletes. The panel members reached a consensus on the following topics: educational topics during rehabilitation; psychological interventions during rehabilitation; additional consultation of the orthopaedic surgeon; duration of postoperative rehabilitation; exercises during phase 1 of nonsurgical and postoperative rehabilitation; criteria for progression from phase 1 to phase 2; resistance training during phase 2; jumping exercises during phase 2; criteria for progression from phase 2 to phase 3; and criteria for return to sports (RTS). The most notable differences in recommendations for prepubertal compared with mid- to postpubertal athletes were described for resistance training and RTS criteria.Conclusion:Together with available evidence, this international Delphi statement provides a framework based on expert consensus and describes a practice guideline for adolescent ACL rehabilitation, which can be used in day-to-day practice. This is an important step toward reducing practice inconsistencies, improving the quality of rehabilitation after adolescent ACL injuries, and closing the evidence-practice gap while waiting for further studies to provide clarity

Recent work on human nature: Beyond traditional essences

Kronfeldner M, Roughley N, Toepfer G. Recent work on human nature: Beyond traditional essences. Philosophy Compass. 2014;9(9):642-652.Recent philosophical work on the concept of human nature disagrees on how to respond to the Darwinian challenge, according to which biological species do not have traditional essences. Three broad kinds of reactions can be distinguished: (1) conservative intrinsic essentialism, which defends essences in the traditional sense, (2) eliminativism, which suggests dropping the concept of human nature altogether, and (3) constructive approaches, which argue that revisions can generate sensible concepts of human nature beyond traditional essences. The different constructive approaches pick out one or two of the three epistemic roles that are fused in traditional essentialist conceptions of human nature: descriptive (descriptivism), explanatory (explanativism), definitional (taxonomic relationalism), or explanatory and definitional (property cluster essentialism). These turns towards diverging epistemic roles are best interpreted pluralistically: there is a plurality of concepts of human nature that have to be clearly distinguished, each with a legitimate role in respective scientific contexts

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO