The bear circadian clock doesn’t ‘sleep’ during winter dormancy

Most biological functions are synchronized to the environmental light:dark cycle via a circadian timekeeping system. Bears exhibit shallow torpor combined with metabolic suppression during winter dormancy. We sought to confirm that free-running circadian rhythms of body temperature (Tb) and activity were expressed in torpid grizzly (brown) bears and that they were functionally responsive to environmental light. We also measured activity and ambient light exposures in denning wild bears to determine if rhythms were evident and what the photic conditions of their natural dens were. Lastly, we used cultured skin fibroblasts obtained from captive torpid bears to assess molecular clock operation in peripheral tissues. Circadian parameters were estimated using robust wavelet transforms and maximum entropy spectral analyses

Measurement in Economics and Social Science

The paper discusses measurement, primarily in economics, from both analytical and historical perspectives. The historical section traces the commitment to ordinalism on the part of economic theorists from the doctrinal disputes between classical economics and marginalism, through the struggle of orthodox economics against socialism down to the cold-war alliance between mathematical social science and anti-communist ideology. In economics the commitment to ordinalism led to the separation of theory from the quantitative measures that are computed in practice: price and quantity indexes, consumer surplus and real national product. The commitment to ordinality entered political science, via Arrow’s ‘impossibility theorem’, effectively merging it with economics, and ensuring its sterility. How can a field that has as its central result the impossibility of democracy contribute to the design of democratic institutions? The analytical part of the paper deals with the quantitative measures mentioned above. I begin with the conceptual clarification that what these measures try to achieve is a restoration of the money metric that is lost when prices are variable. I conclude that there is only one measure that can be embedded in a satisfactory economic theory, free from unreasonable restrictions. It is the Törnqvist index as an approximation to its theoretical counterpart the Divisia index. The statistical agencies have at various times produced different measures for real national product and its components, as well as related concepts. I argue that all of these are flawed and that a single deflator should be used for the aggregate and the components. Ideally this should be a chained Törnqvist price index defined on aggregate consumption. The social sciences are split. The economic approach is abstract, focused on the assumption of rational and informed behavior, and tends to the political right. The sociological approach is empirical, stresses the non-rational aspects of human behavior and tends to the political left. I argue that the split is due to the fact that the empirical and theoretical traditions were never joined in the social sciences as they were in the natural sciences. I also argue that measurement can potentially help in healing this split

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Lunar Surface Systems Supportability Technology Development Roadmap

The Lunar Surface Systems Supportability Technology Development Roadmap is a guide for developing the technologies needed to enable the supportable, sustainable, and affordable exploration of the Moon and other destinations beyond Earth. Supportability is defined in terms of space maintenance, repair, and related logistics. This report considers the supportability lessons learned from NASA and the Department of Defense. Lunar Outpost supportability needs are summarized, and a supportability technology strategy is established to make the transition from high logistics dependence to logistics independence. This strategy will enable flight crews to act effectively to respond to problems and exploit opportunities in an environment of extreme resource scarcity and isolation. The supportability roadmap defines the general technology selection criteria. Technologies are organized into three categories: diagnostics, test, and verification; maintenance and repair; and scavenge and recycle. Furthermore, "embedded technologies" and "process technologies" are used to designate distinct technology types with different development cycles. The roadmap examines the current technology readiness level and lays out a four-phase incremental development schedule with selection decision gates. The supportability technology roadmap is intended to develop technologies with the widest possible capability and utility while minimizing the impact on crew time and training and remaining within the time and cost constraints of the program

The Ursinus Weekly, November 25, 1963

John F. Kennedy buried at Arlington today: Assassination saddens world • Students react to news of murder • Assassination historically • President\u27s life in review • A statement about John Kennedy • Oswald murdered Sunday • Chapel service held in memory of Kennedy • Editorial: Riderless horse; Reign of reason • Letters to the editor • Students petition for corrective measures at 6th Ave. & Main St. • Candace Sprecher struck by auto • Student editors at Scranton\u27s press conference • Messiah to be presented Dec. 12 • Tara theme of Senior Ball • Donald Barnhouse, TV 10 newscaster to speak • Soviets speak at Phila. Council: UC students question • College group visits Saint Gabriels • Lyndon Baines Johnson sworn in as 36 President Friday November 22, 1963 • Lecture presented on Rome Council • Greek gleanings • Curtain Club\u27s first theatre in round production December 6 • Teacher exams to be given Feb. 15https://digitalcommons.ursinus.edu/weekly/1259/thumbnail.jp

A multi-decade record of high quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) “living data” publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770. The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID

Input-specific control of reward and aversion in the ventral tegmental area

Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (γ-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.National Institutes of Health (U.S.) (Grant NIH NS069375)JPB FoundationNational Institute of Mental Health (U.S.

Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.37