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The uprooting and displacement of people has long been among the hardships associated with development and modernity. Indeed, the circulation of commodities, currency, and labor in modern society necessitates both social and spatial mobility. However, the displacement and resettlement of millions of people each year by large-scale infrastructural projects raises serious questions about the democratic character of the development process. Although designed to spur economic growth, many of these projects leave local people struggling against serious impoverishment and gross violations of human rights. Working from a political-ecological perspective, Anthony Oliver-Smith offers the first book to document the fight against involuntary displacement and resettlement being waged by people and communities around the world. Increasingly over the last twenty-five years, the voices of people at the grass roots are being heard. People from many societies and cultures are taking action against development-forced displacement and resettlement (DFDR) and articulating alternatives. Taking the promise of democracy seriously, they are fighting not only for their place in the world, but also for their place at the negotiating table, where decisions affecting their well-being are made.

A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.

Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST). This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups. 64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation. Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain. ClinicalTrials.gov NCT00755573.

Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients' pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive (physical-) examination by the physician is still obligate.

Efficient protein secretion from yeast is essential for the bioeconomy.We employed Combinatorial Golden Gate cloning to create more than 6000 expression constructs.A G-protein-coupled receptor (GPCR) biosensor was used to identify the best secreting clones.The biosensor rapidly finds the best signal peptide sequence to secrete a target protein efficiently. Secretion of high-value proteins and enzymes is fundamental to the synthetic biology economy, allowing continuous fermentation during production and protein purification without cell lysis. Most eukaryotic protein secretion is encoded by an N-terminal signal peptide (SP); however, the strong impact of SP sequence variation on the secretion efficiency of a given protein is not well defined. Despite high natural SP sequence diversity, most recombinant protein secretion systems use only a few well-characterised SPs. Additionally, the selection of promoters and terminators can significantly affect secretion efficiency, yet screening numerous genetic constructs for optimal sequences remains inefficient. Here, we adapted a yeast G-protein-coupled receptor (GPCR) biosensor, to measure the concentration of a peptide tag that is co-secreted with any protein of interest (POI). Thus, protein secretion efficiency can be quantified via induction of a fluorescent reporter that is upregulated downstream of receptor activation. This enabled high-throughput screening of over 6000 combinations of promoters, SPs, and terminators, assembled using one-pot Combinatorial Golden Gate cloning. We demonstrate this biosensor can quickly identify best combinations for secretion and quantify secretion levels. Our results highlight the importance of SP optimisation as an initial step in designing heterologous protein expression strategies, demonstrating the value of high-throughput screening (HTS) approaches for maximising secretion efficiency. [Display omitted] We have developed a fast and simple way to optimise the secretion of different proteins from yeast using a biosensor. This technology can quickly screen thousands of different genetic combinations to find the best secretion signal peptide sequence. This is important because secreting proteins outside the cell is essential for the industrial production of high-value proteins. The technology readiness level (TRL) of our technology corresponds to TRL 6 according to the NASA standards (system/subsystem model or prototype demonstration in relevant environment). We have demonstrated the effectiveness of our system in rapidly optimising protein secretion within a laboratory strain of Saccharomyces cerevisiae. To increase the TRL, the system must now be demonstrated in an industrial strain of S. cerevisiae and other species of yeast relevant to industrial protein production, such as Komagataella phaffii (formerly Pichia pastoris). Challenges for full-scale implementation include genetic engineering of non-model host strains to replicate the biosensor system. Policy implications include the use of genetically modified organisms in biomanufacturing of pharmaceuticals and food products, for which there are several existing precedents (e.g., for Hepatitis B vaccine production and the recombinant production of leghaemoglobin by Impossible™ Foods).

The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study. Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together. The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis.

Hyperalgesia is a well recognized hallmark of disease. Pro-inflammatory cytokines have been suggested to be mainly responsible, but human data are scarce. Changes in pain threshold during systemic inflammation evoked by human endotoxemia, were evaluated with three quantitative sensory testing methods. Pressure pain thresholds, electrical pain thresholds and tolerance to the cold pressor test were measured before and 2 hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served as controls. Endotoxemia led to a rise in body temperature and inflammatory symptom scores and a rise in plasma TNF-α, IL-6, IL-10 and IL-1RA. During endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced with 20 ± 4 % and 13 ± 3 %, respectively. In controls only a minor decrease in pressure pain thresholds (7 ± 3 %) and no change in electrical pain thresholds occurred. Endotoxin-treated subjects experienced more pain during the cold pressor test, and fewer subjects were able to complete the cold pressor test measurement, while in controls the cold pressor test results were not altered. Peak levels and area under curves of each individual cytokine did not correlate to a change in pain threshold measured by one of the applied quantitative sensory testing techniques. In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception.

Climate change will have a progressively increasing impact on environmental degradation and environmentally dependent socio-economic systems with potential to cause substantial population displacement. The key concerns in Less Developed Countries (LDCs) will include serious threats to food security and health, considerable economic decline, inundation of coastal areas, and degradation of land and fresh water resources (Reuveny in Polit Geogr, 2007). The relationship between environmental change and potential humanitarian crises has been captured by: McGregor (Geography and refugees: patterns and processes of change, Belhaven Press, London, pp 159-70, 1993), Kibreab (Environment and Population Change, International Union for the Scientific Study of Population, Liège, 1994), Kibreab (Disasters 21(1):20-38, 1997), Myers (Bioscience 43:752-761, 1993), Myers and Kent (Environmental exodus: an emergent crisis in the global arena, Climate Institute, Washington, DC, 1995), Black (New Issues in Refugee Research, Working Paper no. 34, 2001), Lee (Environmental matters: conflict, refugees and international relations, World Human Development Institute Press, Seoul and Tokyo, 2001), Castles (Environmental Change and Induced Migration: Making Sense of the Debate Working Paper No. 70, 2002), Christian Aid (Human tide: the real migration crisis, Christian Aid, London, 2007), and Massey et al. (http://www.psc.isr.umich.edu/pubs/pdf/rr07-615.pdf, 2007). However, we know little about the interplay between environmental change and stresses on ecological systems, resulting socio-economic vulnerability and potential outcomes in terms of population displacement or induced migration. So far these relationships are poorly conceptualized, lack systematic investigation, and are reduced to simplistic causal explanations. This leads to misleading conclusions that deny the complex multivariate processes—environmental, political, social, and economic— which are the root causes of environmentally induced migration and/or conflict. When people are faced with severe environmental degradation they have one of three options: (1) stay and adapt to mitigate the effects; (2) stay, do nothing and accept a lower quality of life; or (3) leave the affected area. The process of movement and migration is usually subject to a complex set of push and pull forces, where push forces relate to the source area while pull factors relate to the destination. These forces are in constant flux, as much as environmental change, and interact with socio-economic and political conditions including state or government decision making powers, which can tip the balance at any point by either denying movement or the right to settle elsewhere. The paper focuses on how environmental change and environmental hazards contribute to the migration by exploring the mechanisms through which vulnerability and migration are linked—via livelihoods, relocation policies, and other factors. The paper begins by outlining important definitions of what is environmentally induced migration. The paper also considers the question of whether migration is a process that reduces or increases vulnerability. The paper draws on multidisciplinary literature including ecology, environment, and climate change; sociology of migration; anthropology of displacement; and economics; but also on preliminary from various case studies in Egypt, Vietnam, and Mozambique.

Background and objectivesPrevious studies have documented that high rates of delay discounting are associated with obesity. However, studies utilizing monetary reward experiments typically report no associations, as opposed to positive associations apparent in studies utilising food-reward experiments. Our objective was to investigate the reasons behind the mixed evidence from a methodological perspective using systematic review and meta-analytic methodologies.MethodsSeven databases (EMBASE, MEDLINE, PsycINFO, Scopus, Web of Science, Econlit and IBSS) were systematically searched. Logistic meta-regression was applied to identify the determinants of a significant association and risk of bias was assessed using a modified form of the Newcastle Ottawa cohort scale.ResultsA total of 59 studies were identified, among which 29 studies (49.2%) found a significant positive association and 29 (49.2%) reported no association. A higher proportion of significant and positive associations was reported in those studies utilizing ‘best-practice’ methods (i.e. appropriate measurement models) to estimate monetary delay discounting (15/27; 55.6%) and incentive-compatible experiments (10/16; 62.5%) than those using non-‘best-practice’ methods (14/34; 41.2%) and hypothetical experiments (19/43; 44.2%). All five studies utilizing both ‘best-practice’ methods and incentive-compatible experiments generated a positive and significant relationship. Results from a logistic meta-regression also suggested that studies employing incentive-compatible experiments (OR: 4.38, 95% CI = 1.05–18.33, p value: 0.04), ‘best-practice’ methods (OR: 4.40, 95% CI = 0.88–22.99, p value: 0.07), parametric methods (OR: 3.36, 95% CI = 0.83–13.57, p value: 0.04), those conducted in children/adolescent populations (OR: 3.90, 95% CI = 0.85–17.88, p value: 0.08), and those with larger sample size (OR: 1.91, 95% CI = 1.15–3.18, p value: 0.01) tended to show positive and significant associations between delay discounting and obesity.ConclusionsThis review suggests that the mixed evidence to date is a result of methodological heterogeneity, and that future studies should utilise ‘best practice’ methods.

Placebo and nocebo effects are known to play a key role in treatment effects in a wide variety of conditions. These effects have frequently been investigated with regard to pain and also in other physical sensations, but have hardly been investigated with regard to itch. In addition, neither in pain nor in any other physical sensation, the single and combined contribution of the expectancy mechanisms of conditioning and verbal suggestion have ever been investigated in both placebo and nocebo effects within one design. For the first time, the role of verbal suggestion and conditioning in placebo and nocebo effects on itch was experimentally investigated. Expectations about itch stimuli were induced in healthy subjects by verbal suggestion, conditioning, or a combination of both procedures, and compared with a control group without expectation induction. Itch was induced electrically by means of quantitative sensory testing. Significant placebo and nocebo effects were induced in the group in which combined procedures of conditioning and verbal suggestion were applied in comparison with the control group. The conditioning and verbal suggestion procedures applied individually did not induce significant placebo and nocebo effects when compared with the control group. The results of this study extend existing evidence on different physical sensations, like pain, by showing that also for itch, the combination of conditioning and verbal suggestion is most promising in inducing both placebo and nocebo effects. More research on placebo and nocebo effects at a perceptive and neurobiological level is warranted to further elucidate the common and specific mechanisms underlying placebo and nocebo effects on itch and other physical sensations.