Abstract Cues associated with rewards acquire the ability to engage the same brain systems as rewards themselves. However, reward cues have multiple properties. For example, they not only act as ...predictors of reward capable of evoking conditional responses (CRs), but they may also acquire incentive motivational properties. As incentive stimuli they can evoke complex emotional and motivational states. Here we sought to determine whether the predictive value of a reward cue is sufficient to engage brain reward systems, or whether the cue must also be attributed with incentive salience. We took advantage of the fact that there are large individual differences in the extent to which reward cues are attributed with incentive salience. When a cue (conditional stimulus, CS) is paired with delivery of food (unconditional stimulus, US), the cue acquires the ability to evoke a CR in all rats; that is, it is equally predictive and supports learning the CS–US association in all. However, only in a subset of rats is the cue attributed with incentive salience, becoming an attractive and desirable incentive stimulus. We used in situ hybridization histochemistry to quantify the ability of a food cue to induce c-fos mRNA expression in rats that varied in the extent to which they attributed incentive salience to the cue. We found that a food cue induced c-fos mRNA in the orbitofrontal cortex, striatum (caudate and nucleus accumbens), thalamus (paraventricular, intermediodorsal and central medial nuclei), and lateral habenula, only in rats that attributed incentive salience to the cue. Furthermore, patterns of “connectivity” between these brain regions differed markedly between rats that did or did not attribute incentive salience to the food cue. These data suggest that the predictive value of a reward cue is not sufficient to engage brain reward systems—the cue must also be attributed with incentive salience.
Livers retrieved after circulatory death are associated with an increased incidence of primary nonfunction, early allograft dysfunction, and biliary strictures. The authors report a case of ...preimplant normothermic perfusion of a suboptimal liver from a 57‐year‐old donor after circulatory death who had been hospitalized for 9 days; predonation alanine transaminase level was 63 IU/L, and the period from withdrawal of life‐supporting treatment to circulatory arrest was 150 minutes. After 5 hours of static cold storage, the liver was subject to normothermic machine perfusion with a plasma‐free red cell–based perfusate. Perfusate lactate level fell from 7.2 to 0.3 mmol/L within 74 minutes of ex situ perfusion, at which point perfusate alanine transaminase level was 1152 IU/L and urea concentration was 9.4 mmol/L. After 132 minutes, normothermic perfusion was stopped and implantation begun. After transplantation, the patient made an uneventful recovery and was discharged on day 8; liver biochemistry was normal by day 19 and has remained normal thereafter. Donor common bile duct excised at implantation showed preservation of peribiliary glands, and cholangiography 6 months posttransplantation showed no evidence of cholangiopathy. Preimplant ex situ normothermic perfusion of the liver appears to be a promising way to evaluate a marginal liver before transplantation and may modify the response to ischemia.
The authors report a liver transplant where ex situ normothermic machine perfusion was used to reduce cold ischemia and permit functional assessment of a donation after circulatory death liver before implantation.
Fisheries and aquaculture make a crucial contribution to global food security, nutrition and livelihoods. However, the UN Sustainable Development Goals separate marine and terrestrial food production ...sectors and ecosystems. To sustainably meet increasing global demands for fish, the interlinkages among goals within and across fisheries, aquaculture and agriculture sectors must be recognized and addressed along with their changing nature. Here, we assess and highlight development challenges for fisheries-dependent countries based on analyses of interactions and trade-offs between goals focusing on food, biodiversity and climate change. We demonstrate that some countries are likely to face double jeopardies in both fisheries and agriculture sectors under climate change. The strategies to mitigate these risks will be context-dependent, and will need to directly address the trade-offs among Sustainable Development Goals, such as halting biodiversity loss and reducing poverty. Countries with low adaptive capacity but increasing demand for food require greater support and capacity building to transition towards reconciling trade-offs. Necessary actions are context-dependent and include effective governance, improved management and conservation, maximizing societal and environmental benefits from trade, increased equitability of distribution and innovation in food production, including continued development of low input and low impact aquaculture.
Resistance to artemisinin-based combination therapy (ACT) in the
parasite is threatening to reverse recent gains in reducing global deaths from malaria. While resistance manifests as delayed parasite ...clearance in patients, the phenotype can only spread geographically via the sexual stages and mosquito transmission. In addition to their asexual killing properties, artemisinin and its derivatives sterilize sexual male gametocytes. Whether resistant parasites overcome this sterilizing effect has not, however, been fully tested. Here, we analyzed
clinical isolates from the Greater Mekong Subregion, each demonstrating delayed clinical clearance and known resistance-associated polymorphisms in the
(PfK13
) gene. As well as demonstrating reduced asexual sensitivity to drug, certain PfK13
isolates demonstrated a marked reduction in sensitivity to artemisinin in an
male gamete formation assay. Importantly, this same reduction in sensitivity was observed when the most resistant isolate was tested directly in mosquito feeds. These results indicate that, under artemisinin drug pressure, while sensitive parasites are blocked, resistant parasites continue transmission. This selective advantage for resistance transmission could favor acquisition of additional host-specificity or polymorphisms affecting partner drug sensitivity in mixed infections. Favored resistance transmission under ACT coverage could have profound implications for the spread of multidrug-resistant malaria beyond Southeast Asia.
Two experiments examined event-related potentials (ERPs) and behavioral correlates of categorizing stimuli varying in perceptual similarity to targets. Participants performed a target-detection task ...in which non-target stimuli varied in target similarity but occurred with equivalent probability. The stimuli were variations of a schematic human face comprised of eight distinct features: two eyes, two eyebrows, one nose, one mouth, and two ears. Non-target stimuli that were perceptually similar to targets produced larger P300-like neurophysiological responses than did other non-target stimuli. These effects emerged whether participants’ target was relatively complex (eight features) or quite simple (zero features). Accordingly, the presence of many constituent elements of a test stimulus does not appear necessary to trigger increases in categorical processing of non-targets that are similar to a target. The data further suggest that the P300 amplitude may be used as a good index of perceptual similarity between target and non-target stimuli.
Summary Objective To assess patient preferences for treatment-related benefits and risks associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis ...(OA). Design Using a chronic-illness panel in the United Kingdom, patients 45 years or older with a self-reported diagnosis of OA were eligible to participate in the study. Patient preferences were assessed using a discrete-choice experiment that compared hypothetical treatment profiles of benefits and risks consistent with NSAID use. Benefit outcomes (ambulatory pain, resting pain, stiffness, and difficulty doing daily activities) were presented on a 0-to-100 mm scale. Risk outcomes (bleeding ulcer, stroke, and myocardial infarction MI) were expressed as probabilities over a fixed time period. Each patient answered 10 choice tasks comparing different treatment profiles. Preference weights were estimated using a random-parameters logit model. Results Final sample included 294 patients. Patients ranked reductions in ambulatory pain and difficulty doing daily activities (both: 6.32; 95% confidence interval CI: 5.0–7.6) as the most important benefit outcomes, followed by reductions in resting pain (2.80; 95% CI: 1.8–3.8) and stiffness (2.65; 95% CI: 0.9–4.4). Incremental changes (3%) in the risk of MI or stroke were assessed as the most important risk outcomes (10.00; 95% CI: 8.2–11.8; and 8.90; 95% CI: 7.3–10.5, respectively). Conclusion Patients ranked ambulatory pain as a more important benefit than resting pain; likely due to its impact on ability to do daily activities. For a 25-mm reduction, patients were willing to accept four times the risk of MI in ambulatory pain vs resting pain.
The India-France SARAL/AltiKa mission is the first Ka-band altimetric mission dedicated to oceanography. The mission objectives are primarily the observation of the oceanic mesoscales but also ...include coastal oceanography, global and regional sea level monitoring, data assimilation, and operational oceanography. The mission ended its nominal phase after 3 years in orbit and began a new phase (drifting orbit) in July 2016. The objective of this paper is to provide a state of the art of the achievements of the SARAL/AltiKa mission in terms of quality assessment and unique characteristics of AltiKa data. It shows that the AltiKa data have similar accuracy at the centimeter level in term of absolute water level whatever the method (from local to global) and the type of water surfaces (ocean and lakes). It shows also that beyond the fact that AltiKa data quality meets the expectations and initial mission requirements, the unique characteristics of the altimeter and the Ka-band offer unique contributions in fields that were previously not fully foreseen.
The leishmaniases are a group of four vector-borne neglected tropical diseases caused by 20 species of protozoan parasites of the genus Leishmania and transmitted through a bite of infected female ...phlebotomine sandflies. Endemic in over 100 countries, the four types of leishmaniasis-visceral leishmaniasis (VL) (known as kala-azar), cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and post-kala-azar dermal leishmaniasis (PKDL)-put 1.6 billion people at risk. In Kenya, the extent of leishmaniasis research has not yet been systematically described. This knowledge is instrumental in identifying existing research gaps and designing appropriate interventions for diagnosis, treatment, and elimination.
This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to determine the state of leishmaniases research in Kenya and identify research gaps. We searched seven online databases to identify articles published until January 2022 covering VL, CL, MCL, and/or PKDL in Kenya. A total of 7,486 articles were found, of which 479 underwent full-text screening, and 269 met our eligibility criteria. Most articles covered VL only (n = 141, 52%), were published between 1980 and 1994 (n = 108, 39%), and focused on the theme of "vectors" (n = 92, 34%). The most prevalent study types were "epidemiological research" (n = 88, 33%) tied with "clinical research" (n = 88, 33%), then "basic science research" (n = 49, 18%) and "secondary research" (n = 44, 16%).
While some studies still provide useful guidance today, most leishmaniasis research in Kenya needs to be updated and focused on prevention, co-infections, health systems/policy, and general topics, as these themes combined comprised less than 4% of published articles. Our findings also indicate minimal research on MCL (n = 1, <1%) and PKDL (n = 2, 1%). We urge researchers to renew and expand their focus on these neglected diseases in Kenya.
Aims/hypothesis Recent work has identified the important roles of M1 pro-inflammatory and M2 anti-inflammatory macrophages in the regulation of insulin sensitivity. Specifically, increased numbers of ...M2 macrophages and a decrease in M1 macrophages within the adipose tissue are associated with a state of enhanced insulin sensitivity. IL-10 is an anti-inflammatory cytokine and is a critical effector molecule of M2 macrophages. Methods In the present study, we examined the contribution of haematopoietic-cell-derived IL-10 to the development of obesity-induced inflammation and insulin resistance. We hypothesised that haematopoietic-cell-restricted deletion of IL-10 would exacerbate obesity-induced inflammation and insulin resistance. Lethally irradiated wild-type recipient mice receiving bone marrow from either wild-type or Il10-knockout mice were placed on either a chow or a high-fat diet for a period of 12 weeks and assessed for alterations in body composition, tissue inflammation and glucose and insulin tolerance. Results Contrary to our hypothesis, neither inflammation, as measured by the activation of pro-inflammatory stress kinases and gene expression of several pro-inflammatory cytokines in the adipose tissue and liver, nor diet-induced obesity and insulin resistance were exacerbated by the deletion of haematopoietic-cell-derived IL-10. Interestingly, however, Il10 mRNA expression and IL-10 protein production in liver and/or adipose tissue were markedly elevated in Il10-knockout bone-marrow-transplanted mice relative to wild-type bone marrow-transplanted mice. Conclusions/interpretation These data show that deletion of IL-10 from the haematopoietic system does not potentiate high-fat diet-induced inflammation or insulin resistance.
The composition of the planetary boundary layer in regions of deep tropical convection has a profound impact on the Tropical Tropopause Layer (TTL). The Aerosol and Chemical Transport in tropIcal ...conVEction (ACTIVE) aircraft campaign was conducted from November 2005 to February 2006 from Darwin, Australia, to characterize the influence of both monsoonal and localized land‐based deep convection on the composition of the TTL. This paper summarizes the composition of the potential inflow to such convection in terms of aerosol particle size and composition, carbon monoxide, and ozone, as measured in the lowest 4 km of the atmosphere by the NERC Dornier‐228 aircraft during 28 flights in different meteorological regimes over the course of ACTIVE. Six contrasting periods are identified in the boundary layer background as a result of the prevailing meteorology and sources of pollution. The campaign began with a relatively polluted and variable biomass burning season in November, followed by a transition to the monsoon season through December with much less burning. A clean maritime flow dominated the wet‐active, and dry‐inactive, monsoon period in January; it was followed by a monsoon break period in February, with a return to continental flow and a more premonsoon background state. Deep convective systems, capable of transporting boundary layer air to the TTL, were observed daily outside of the monsoon periods. The chemical composition of submicron aerosols in the premonsoon periods was dominated by a mix of fresh and aged organic material with significant black carbon, well‐correlated with carbon monoxide indicating a common burning source, while marine aerosol during the monsoon changed markedly between the wet and dry phases. High concentrations of coarse‐mode aerosols were also observed in the monsoon: the clean, marine air masses and high surface winds imply that sea salt may be the dominant aerosol type under these conditions. The climatology presented here will provide a valuable data set for model simulation of chemical and aerosol transport by deep convection in the Darwin region.
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