Bird collisions in a railway crossing a wetland of international importance (Sado estuary, Portugal)

L. Borda-de-Água et al. (eds.), Railway Ecology, chapter 7, p. 103-115Many studies have evaluated bird mortality in relation to roads and other human structures, but little is known about the potential impacts of railways. In particular, it is uncertain whether railways are an important mortality source when crossing wetlands heavily used by aquatic birds. Here we analyze bird collisions in a railway that crosses the Nature Reserve of the Sado Estuary (Portugal) over an annual cycle, documenting bird mortality and the flight behaviour of aquatic birds in relation to a bowstring bridge. During monthly surveys conducted on 16.3 km of railway, we found 5.8 dead birds/km/10 survey days in the section crossing wetland habitats (6.3 km), while <0.5 dead birds/km/10 survey days were found in two sections crossing only forested habitats. Most birds recorded were small songbirds (Passeriformes), while there was only a small number of aquatic birds (common moorhen, mallard, flamingo, great cormorant, gulls) and other non-passerines associated with wetlands (white stork). During nearly 400 h of observations, we recorded 27,000 movements of aquatic birds across the Sado bridge, particularly in autumn and winter. However, only <1% of movements were within the area of collision risk with trains, while about 91% were above the collision risk area, and 8% were below the bridge. Overall, our case study suggests that bird collisions may be far more numerous in railways crossing wetland habitats than elsewhere, although the risk to aquatic birds may be relatively low. Information from additional study systems would be required to evaluate whether our conclusions apply to other wetlands and railway linesinfo:eu-repo/semantics/publishedVersio

Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

BACKGROUND: New antimalarial regimens, including artemisinin-based combination therapies (ACTs), have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. CASE DESCRIPTION: Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. DISCUSSION AND EVALUATION: Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. CONCLUSION: Although the World Health Organization has supported the development of pharmacovigilance systems in African countries deploying ACTs, additional guidance on adverse events monitoring in antimalarial clinical trials is needed, similar to the standardized recommendations available for assessment of drug efficacy

Exercise therapy for prevention of falls in people with Parkinson's disease: A protocol for a randomised controlled trial and economic evaluation

<p>Abstract</p> <p>Background</p> <p>People with Parkinson's disease are twice as likely to be recurrent fallers compared to other older people. As these falls have devastating consequences, there is an urgent need to identify and test innovative interventions with the potential to reduce falls in people with Parkinson's disease. The main objective of this randomised controlled trial is to determine whether fall rates can be reduced in people with Parkinson's disease using exercise targeting three potentially remediable risk factors for falls (reduced balance, reduced leg muscle strength and freezing of gait). In addition we will establish the cost effectiveness of the exercise program from the health provider's perspective.</p> <p>Methods/Design</p> <p>230 community-dwelling participants with idiopathic Parkinson's disease will be recruited. Eligible participants will also have a history of falls or be identified as being at risk of falls on assessment. Participants will be randomly allocated to a usual-care control group or an intervention group which will undertake weight-bearing balance and strengthening exercises and use cueing strategies to address freezing of gait. The intervention group will choose between the home-based or support group-based mode of the program. Participants in both groups will receive standardized falls prevention advice. The primary outcome measure will be fall rates. Participants will record falls and medical interventions in a diary for the duration of the 6-month intervention period. Secondary measures include the Parkinson's Disease Falls Risk Score, maximal leg muscle strength, standing balance, the Short Physical Performance Battery, freezing of gait, health and well being, habitual physical activity and positive and negative affect schedule.</p> <p>Discussion</p> <p>No adequately powered studies have investigated exercise interventions aimed at reducing falls in people with Parkinson's disease. This trial will determine the effectiveness of the exercise intervention in reducing falls and its cost effectiveness. This pragmatic program, if found to be effective, has the potential to be implemented within existing community services.</p> <p>Trial registration</p> <p>The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12608000303347).</p

Choosing a medical specialty: the difference between what students want and what society needs

The choice of a specialty by medical students is a complex one that has significant implications for the future supply of physician manpower. The study by Weissman et al. portrays this choice as reflecting the degree of congruence between a student’s needs and values and his or her perception of the characteristics of the various specialties. The existing shortages in the supply of various specialists in Israel may be interpreted as signifying a lack of alignment of student needs and perceptions. This commentary will extend the implications of this work to include the connection between students’ choices and the physician manpower needs of society, and will focus on primary care physician shortages in the United States as but one example of the implications of these relationships

Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats

<p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C_maxand AUC_0-∞values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C_maxand the AUC_0-tvalues for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10^-5cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p

The association between misperceptions around weight status and quality of life in adults in Australia

Objective: Limited evidence supports a possible association between a person’s perception of their weight status and their quality of life (QoL). This study evaluates whether misperception around weight status is associated with QoL and the impact of gender on this association. Methods: A cross-sectional survey of Australian adults (n=1,905 analysed) collected selfreported height and weight (used to estimate BMI), gender and QoL (described using the AQoL-8D). Participants reported whether they perceived their weight status to be ‘underweight’, ‘healthy weight’, ‘overweight’ or ‘obese’. Misperception around weight status was categorised based on perceived weight status and self-reported BMI. Ordinary least squares regression was used to test associations between self-reported overall, physical and psychosocial QoL, misperception of weight status, and gender, across different BMI categories, after controlling for income, education, relationship status and health conditions. Results: Compared to accurate perception, underestimation of weight status was associated with higher overall QoL for obese males and females and for overweight males. Overestimation of weight status was associated with higher overall QoL for underweight females and lower overall QoL for healthy weight males and females. The same pattern was seen for psychosocial QoL. Physical QoL was less sensitive to misperception than psychosocial QoL. Conclusions: Self-reported misperception around weight status is associated with overall, psychosocial and to a lesser extent physical QoL in Australian adults, although its role depends on BMI category and gender. Generally misperception in the direction of “healthy weight” is associated with higher QoL and overestimation of weight status by those who are of healthy weight is associated with lower QoL. Findings should be confirmed in datasets that contain measured as opposed to self-report height and weight

Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models

Circulating CD14brightCD16+ 'intermediate' monocytes exhibit enhanced parasite pattern recognition in human helminth infection.

Circulating monocyte sub-sets have recently emerged as mediators of divergent immune functions during infectious disease but their role in helminth infection has not been investigated. In this study we evaluated whether 'classical' (CD14brightCD16-), 'intermediate' (CD14brightCD16+), and 'non-classical' (CD14dimCD16+) monocyte sub-sets from peripheral blood mononuclear cells varied in both abundance and ability to bind antigenic material amongst individuals living in a region of Northern Senegal which is co-endemic for Schistosoma mansoni and S. haematobium. Monocyte recognition of excretory/secretory (E/S) products released by skin-invasive cercariae, or eggs, of S. mansoni was assessed by flow cytometry and compared between S. mansoni mono-infected, S. mansoni and S. haematobium co-infected, and uninfected participants. Each of the three monocyte sub-sets in the different infection groups bound schistosome E/S material. However, 'intermediate' CD14brightCD16+ monocytes had a significantly enhanced ability to bind cercarial and egg E/S. Moreover, this elevation of ligand binding was particularly evident in co-infected participants. This is the first demonstration of modulated parasite pattern recognition in CD14brightCD16+ intermediate monocytes during helminth infection, which may have functional consequences for the ability of infected individuals to respond immunologically to infection

Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.Clinicaltrials.gov NCT01155492