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Why does Mary learn something when she leaves the room? One answer, endorsed by some physicalists as well as most dualists, is as follows. Mary learns something because phenomenal knowledge requires direct acquaintance with phenomenal properties. For this reason, there is an epistemic gap between the physical and the phenomenal: phenomenal facts cannot be deduced from physical facts. This is the acquaintance response to the Knowledge Argument. The physicalist and dualist versions of the acquaintance response diverge as to whether this epistemic gap reveals an ontological gap between the physical and the phenomenal.
Systematic reviews have developed over the past 40 years as a method for integrating findings from the available studies relating to clinical problems and interventions into one publication. Systematic reviews employ a variety of data analytic techniques including meta-analysis, which combines treatment effects across disparate studies in order to produce a truer estimate of treatment effect. The Cochrane Collaboration was established in order to facilitate access to high-quality evidence and specifies stringent guidelines for the production of systematic reviews. A Cochrane Systematic Review (CSR) includes consideration of the risk-of-bias of the selected studies in reaching conclusions. A recent CSR is used as an example to demonstrate the process of conducting a CSR, the data analytic methods employed and the assumptions made when employing these methods. There is a discussion of issues the reader will need to be aware of when considering the findings of a CSR and how this might differ from other systematic reviews including some consideration of how CSRs apply to the brain impairment literature.
Transparency of research is a large concern in political science, and the practice of publishing links to datasets and other online resources is one of the main methods by which political scientists promote transparency. But the method cannot work if the links don’t, and very often, they don’t. We show that most of the URLs ever published in the American Political Science Review no longer work as intended. The problem is severe in recent as well as in older articles; for example, more than one-fourth of links published in the APSR in 2013 were broken by the end of 2014. We conclude that “reference rot” limits the transparency and reproducibility of political science research. We also describe practices that scholars can adopt to combat the problem: when possible, they should archive data in trustworthy repositories, use links that incorporate persistent digital identifiers, and create archival versions of the webpages to which they link.
Ruminants remain productive during the energy insufficiency of late pregnancy or early lactation by evoking metabolic adaptations sparing available energy and nutrients (e.g. higher metabolic efficiency and induction of insulin resistance). A deficit in central leptin signaling triggers these adaptations in rodents but whether it does in ruminants remains unclear. To address this issue, five mature ewes were implanted with intracerebroventricular (ICV) cannula in the third ventricle. They were used in two experiments with an ovine leptin antagonist (OLA) when well-conditioned (average body condition score of 3.7 on a 5 point scale). The first experiment tested the ability of OLA to antagonize leptin under in vivo conditions. Ewes received continuous ICV infusion of artificial cerebrospinal fluid (aCSF), ovine leptin (4 µg/h) or the combination of ovine leptin (4 µg/h) and its mutant version OLA (40 µg/h) for 48 h. Dry matter intake (DMI) was measured every day and blood samples were collected on the last day of infusion. ICV infusion of leptin reduced DMI by 24% (P<0.05), and this effect was completely abolished by OLA co-infusion. A second experiment tested whether a reduction in endogenous leptin signaling in the brain triggers metabolic adaptations. This involved continuous ICV infusions of aCSF or OLA alone (40 µg/h) for 4 consecutive days. The infusion of OLA did not alter voluntary DMI over the treatment period or on any individual day. OLA did not affect plasma variables indicative of insulin action (glucose, non-esterified fatty acids, insulin and the disposition of plasma glucose during an insulin tolerance test) or plasma cortisol, but tended to reduce plasma triiodothyronine and thyroxine (P<0.07). Overall, these data show that a reduction of central leptin signaling has little impact on insulin action in well-conditioned mature sheep. They also raise the possibility that reduced central leptin signaling plays a role in controlling thyroid hormone production.
Within the field of innovation studies and technological change, the distinction between tacit and codified knowledge has recently been accorded great significance. Much of this interest was stimulated by Nelson and Winter (1982), whose classic work An Evolutionary Theory of Economic Change made extensive use of the concept of tacit knowledge in their analysis of how organizational routines shape technological change. In so doing, these authors have helped revive widespread interest in the earlier work of Michael Polanyi (1958, 1966), to the point where tacit knowledge has come to be recognized as a central component of the learning economy (Lundvall and Johnson 1994) and a key to innovation and value creation.
Moreover, tacit knowledge has come to be acknowledged as a prime determinant of the geography of innovative activity, since its central role in the process of learning-through-interacting tends to reinforce the local over the global. Those interested in the geographical structure of production and innovation systems have argued that the strong tacit component of leading-edge technical knowledge induces (indeed, requires) spatial clustering for the purposes of knowledge sharing that leads to innovation (Cooke and Morgan 1998; Maskell and Malmberg 1999). For a growing number of scholars, this explains the perpetuation and deepening of geographical concentration in a world of expanding markets, weakening borders, and ever-cheaper and more pervasive communication technologies.
To explore anthropometric indicators and mental development in very-low-income children in the second year of life.
Low-income areas (income <20th percentile) in semi-urban Mexico (defined as towns or cities with 2500–50 000 inhabitants).
Eight hundred and ninety-six children aged 12.5–23.5 months surveyed from September to December 2001.
Questionnaire survey and anthropometric survey of households. Multivariate regression models evaluated differences across age in anthropometry (height-for-age Z-score (HAZ) and weight-for-height Z-score) and cognitive function (Mental Development Index (MDI) of the Bayley Scales of Infant Development) while controlling for socio-economic and parental characteristics.
There was a significant decline in HAZ and in age-adjusted MDI score across the second year of life. Although the children showed MDI scores close to the mean, normed US values at 13–14 months, the scores were significantly lower than expected in older children (P < 0.0001), even after controlling for socio-economic status and parental characteristics. At 13–14 months, only 3% of children received scores below 70 (less than minus two standard deviations), whereas by 19–20 months, almost 17% of children were performing below this level. No socio-economic or parental characteristics were significant predictors of HAZ or MDI.
Parallel deficits are evident in both height-for-age and cognitive functioning during the second year of life in low-income Mexican infants. The consistency of these growth and development findings further stresses the need for targeted interventions to reduce the vulnerability of low-income Mexican children very early in life.
Despite the prevalence of psychiatric illness in people with acquired brain injury (ABI), there are very few empirically validated studies examining the efficacy of treatments targeting commonly occurring disorders such as depression and anxiety. Using a randomised controlled trial, this study evaluated the efficacy of a cognitive behavioural intervention specifically designed for managing social anxiety following ABI. Twelve brain-injured participants were screened, randomly allocated to either treatment group (TG) or a wait list group (WLG), and proceeded through to the final stages of therapy. The TG received between 9 and 14 hourly, individual sessions of cognitive behavioural therapy. Repeated measures analyses revealed significant improvements in general anxiety, depression and a transient mood measure, tension-anxiety, for the TG when compared to the WLG at posttreatment. These treatment gains were maintained at one-month follow-up. Although in the predicted direction, postintervention improvements in social anxiety and self-esteem for the TG were not significant in comparison with the WLG. This study lends support to the small body of literature highlighting the potential of cognitive behavioural interventions for managing the psychological problems that serve as a barrier to rehabilitation following ABI.
Fluorescence resonance energy transfer (FRET) microscopy was used to study interactions between proteins in intact cells. We showed that growth hormone (GH) causes transient homodimerization of GH receptors tagged with yellow or cyan fluorescent proteins. The peak of FRET signaling occurred 2 to 4 min after hormonal stimulation and was followed by a decrease in FRET signal. Repeating those experiments in cells pretreated with the inhibitor of internalization methyl-β-cyclodextrin, or in potassium-depleted cells showed no difference in the kinetics of FRET signaling as compared with the non-treated cells, indicating that the decrease in FRET signal does not result from receptor internalization by the pathways inhibited by methyl-β-cyclodextrin or potassium depleted but might occur by other pathways of internalization. Using a similar methodology, we also demonstrated that ovine placental lactogen (oPL) causes transient heterodimerization of GH and prolactin (PRL) receptors 2·5 to 3 min after oPL application. On the other hand, oGH or oPRL had no effect at all, further substantiating the finding the oPL, which lacks a specific receptor, acts in homologous systems by heterodimerization of GH and PRL receptors. We also demonstrated that both PRL and leptin (LEP) are capable of transactivation of the oncogenic receptors erbB2 and erbB3. Upon PRL or LEP stimulation of HEK-293T cells transfected with LEP or PRL receptors and erbB2 or erbB3, erbB proteins are first phosphorylated and then activate MAPK (erk1/erk2). However, the FRET experiments failed to document any evidence of a direct interaction between erbB2 and the PRL or LEP receptors, suggesting that erbB activation probably occurs via activated JAK2, translocated from the respective receptors to erbB2.
It's always a pleasure to read a paper by Charles Goodhart, who brings a unique blend of academic rigor and originality, frontline experience, and plain common sense to his musings on central banking. Goodhart points out that the controlling consensus for monetary policy is that it should be focused on achieving and maintaining price stability over time. Both economic theory and experience indicate that prolonged deviations from reasonable price stability—in either direction—can have serious negative implications for economic performance.
Goodhart highlights a number of issues that arise in implementing policy within this framework. I'm not going to comment directly on Goodhart's paper. Rather, reading the paper sparked my own musings on some areas that might benefit from further research, and I thought that with the Federal Reserve Bank of Cleveland launching its Central Bank Institute, this might be an opportune moment for such a discussion. There is considerable overlap between Goodhart's topics and my own; in large measure he was my inspiration, though in some cases we come at the same subject from different angles. I call this comment “Whither Central Banking Research?” Obviously, my list is not a complete research agenda; rather, it covers four topics that have caught my attention in my work with the Federal Reserve, reinforced in some cases by my experience at the Bank of England.
With the gavelling of the accession package at the conclusion of the Working Party meeting on 17 September 2001, the negotiation on China's accession to the WTO was finally brought to a close. Thereafter, the WTO Ministerial Conference approved the terms of China's accession in Doha (Qatar) on 10 November 2001 and the Chinese government notified its acceptance on 11 November. In line with customary practice, and as set out in China's Protocol of Accession, China became a member of the WTO thirty days later, on 11 December 2001.
Each accession to the WTO is a unique event, but few would argue with the proposition that China's accession is in a class of its own. After all, China was one of the twenty-three original Contracting Parties to the GATT in 1948 and her application for readmission to the multilateral trading system dates back fifteen years to July 1986, easily making it the longest and most arduous accession negotiation in the history of the GATT/WTO.
After China's revolution in 1949 and the split between Mao Zedong and Chiang Kai-Shek, the government in Taiwan announced in 1950 that China would leave the GATT. Although the government in Beijing never recognized this withdrawal decision, nearly forty years later, in 1986, the People's Republic of China notified the GATT of its wish to resume its status as a GATT Contracting Party and its willingness to renegotiate the terms of its membership.
Pregnancy and lactation are phases during which major adaptations in maternal metabolism are necessary to meet the requirements of foetal growth and of lactation. Leptin, an adipocyte derived hormone, involved in regulation of energy metabolism, has been implicated in the coordination of these adaptive processes. Similar to monogastric species, increased leptin blood concentrations are reported for sheep at mid-pregnancy when compared to prebreeding, late pregnancy or early lactation (Ehrhardt et al., 2001). In sheep, the changes of leptin concentrations showed no obvious relation with the ability of insulin to promote glucose utilisation (Ehrhardt et al., 2001). With the study presented herein, we aimed to elucidate whether exogenous leptin modulates insulin responsiveness and whether the responsiveness is dependent of the physiological status of the animal. Using specific clamp techniques i.e. glucose infusion studies to quantify insulin secretion and resistance, we compared the effect of leptin application on glucose metabolism in pregnant versus lactating goats.
Obese protein (OB) also known as leptin serves as a protein signal secreted from adipose tissue and acts on a central nervous system that regulate ingestive behavior and energy balance (Campfield, 2000). The sequence of various leptins from 10 mammalian species was compiled and the 3D structure of human leptin mutant W100E was elucidated (Zhang et al., 1997). We have prepared recombinant leptins of sheep, chicken, cow and pig. Mammalian and chicken leptins are respectively 146 and 145 amino acid containing proteins found in circulation. Leptin in blood is found in both free and bound form; the main binding protein is the extracellular domain (ECD) of leptin receptor (Liu et al., 1997). One of the established functions of leptin, is its attenuating effect on the expression of NPY and other neuropeptides in hypothalamus that subsequently leads to decreased food intake (Campfield, 2000). Therefore it seems logical that blocking leptin receptors that are responsible for transferring it through the blood-brain barrier or for its action in hypothalamus will lead to increase in food intake. Leptin receptor belongs to cytokine receptor superfamily. Its ECD consists of ∷ 800 amino acids but it was suggested that only the cytokine homology subdomain II (CHD) consisting of ∷ 200 amino acids is responsible for binding (Fong et al., 1997). The objective of the present work is to prepare recombinant proteins aimed to block leptin action. We suggest two approaches (a) preparation of leptin antagonists capable of binding but not homodimerizing leptin receptors and (b) subcloning and preparing CHD II of leptin receptor responsible for binding of the hormone.
In mammals leptin plays a key role in regulating the whole-body energy homeostasis and is important for for normal reproduction Much evidence indicates that leptin mediates the undernutrition-induced alterations of the reproductive axis (Ahima and Flier, 2000). In birds leptin gene was cloned in chickens (Taouis et al., 1998) and recombinant chicken leptin (chLep) was prepared in our laboratory (Raver et al., 1998). Unlike mammals, leptin is expressed not only in the adipose tissue but also in liver and leptin plasma level is lower in fasted than in fed hens (Dridi et al., 2000). However, the importance of leptin in avian reproduction is not known. Therefore, the aim of the present study was to examine whether in chickens leptin affects events occuring in the ovary during fasting.
As recently as 1960, a child born into poverty anywhere in the world had only a one-in-four chance of reaching his fifth birthday, while a person age 15 had a life expectancy of 67 years. Today, vaccines protect eight out of ten of the world's children, more than nine out of ten infants will enroll in school, and the average adult will live into his eighth decade. Around the world, the health gains made in the past two generations are arguably the greatest accomplishment of civilization. What makes these gains so remarkable is that they have been accomplished by people living on every continent on the globe—people representing a panoply of cultures, social structures, and values. Amid this diversity, there is a consistent belief that all societies, and the governments that represent them, are responsible for improving the well-being of the population.
In the health sector, this responsibility means understanding the many factors that go into improving people's health. Some of the most important factors—such as national economic development, education, particularly of women, and the creation of technologies that lead to more effective clinical care—lie outside of what is typically viewed as the health sector. Although these factors are not directly involved with the financing, organization, and delivery of health care, they are substantive sectoral inputs into any country's effort to create better health for its population, and, thus, need to be understood in any health policy context.