Ecological risk assessments to guide decision-making: Methodology matters

Ecological risk assessment is often applied to guide the decision-making process that underpins ecosystem-based management and prioritisation of risk factors for management. Several studies have recently used ecological risk assessment approaches to identify risk factors of greatest concern, but rarely are the underlying methodological decisions discussed in terms of the effect that those decisions have on the outcome of the assessment and ultimately, how that affects prioritisation of risk factors for management. This study therefore evaluates the effect of methodological decisions involving (1) the choice and definition of risk factors, and (2) the calculation of risk scores, providing, where possible, recommendations on what should be the most appropriate methodologies. The definition of risk factors is often determined by the policy context and could result in the comparison of one broadly defined risk meta-factor (e.g. Food Production) with corresponding specific risk factors defined more narrowly (i.e. Oil and Gas production or Offshore Wind). Depending on the method to calculate risk this may result in a systematic bias prioritising any risk meta-factor. For the calculation of individual impact chain risk scores we compared weighted scores with ordinal scores, where the former allows more flexibility to represent the qualitative categories that determine risk and provided results better supported by scientific evidence. A consideration of different risk assessment applications in EBM showed there is no one-size-fits-all solution to this as these methodological decisions need to be considered in concert and the preferred methodology may depend on the context in which the risk assessment is applied. The outcome of the risk assessment should always be accompanied by an explicit consideration of these methodological issues and description of the resulting methodological choices

Sexually dimorphic role for vasopressin in the development of social play

Despite the well-established role of vasopressin (AVP) in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of play. Unexpectedly, play emerged more rapidly in weanling-aged females than in males, resulting in a sex difference opposite of that typically reported for older, juvenile rats. AVP mRNA and play were correlated in males only, with a negative correlation in the bed nucleus of the stria terminalis and a positive correlation in the paraventricular nucleus of the hypothalamus. These findings support the hypothesis that AVP acts differentially on multiple systems in a sex-specific manner to regulate social play and suggest a role for PVN and BNST AVP systems in the development of play. Differential neuropeptide regulation of male and female social development may underlie well-documented sex differences in incidence, progression, and symptom severity of behavioral disorders during development

Familial Cervical Cancer: Case Reports, Review and Clinical Implications

We report three Dutch families with familial clustering of (pre)neoplastic cervical disease, review the literature on familial risks of cervical intraepithelial neoplasia (CIN) and cervical cancer, and discuss possible practical guidelines for women with a family history of cervical cancer. Daughters and sisters of women with cervical cancer have been reported to have a relative risk of 1.5-2.3 to develop this type of cancer. From a practical clinical point of view, we suggest that as in women with an increased non-genetic risk to develop cervical cancer (e.g. because of immunosuppressive therapy) increased surveillance to detect this tumour should be considered in women with an increased risk based on family history. Cessation of smoking should be advised. As the use of condoms at least prevents HPV re-infection its use can be recommended as a way to lower the cervical cancer risk. Future studies to determine the genetic contribution to the development of cervical cancer should include the paternal family history of cancer and, because genetic predisposition might express itself as a higher risk to develop precursors of cervical cancer, carcinoma in situ and CIN grade II-III

Evaluation of ecosystem-based marine management strategies based on risk assessment

Abstract This study presents a comprehensive and generic framework that provides a typology for the identification and selection of consistently defined ecosystem-based management measures and allows a coherent evaluation of these measures based on their performance to achieve policy objectives. The performance is expressed in terms of their reduction of risk of an adverse impact on the marine ecosystem. This typology consists of two interlinked aspects of a measure, i.e. the “Focus” and the “Type”. The “Focus” is determined by the part of the impact chain (Driver–Pressure–State) the measure is supposed to mitigate or counteract. The “Type” represents the physical measure itself in terms of how it affects the impact chain directly; we distinguish Spatio-temporal distribution controls, Input and Output controls, Remediation and Restoration measures. The performance of these measures in terms of their reduction in risk of adverse impacts was assessed based on an explicit consideration of three time horizons: past, present and future. Application of the framework in an integrated management strategy evaluation of a suite of measures, shows that depending on the time horizon, different measures perform best. “Past” points to measures targeting persistent pressures (e.g. marine litter) from past activities. “Present” favors measures targeting a driver (e.g. fisheries) that has a high likelihood of causing adverse impacts. “Future” involves impacts that both have a high likelihood of an adverse impact, as well as a long time to return to pre-impacted condition after the implementation of appropriate management, e.g. those caused by permanent infrastructure or persistent pressures such as marine litter or specific types of pollution

Physicochemical-guided design of cathelicidin-derived peptides generates membrane active variants with therapeutic potential.

The spread of multi-drug resistance and the slow pace at which antibiotics come onto the market are undermining our ability to treat human infections, leading to high mortality rates. Aiming to overcome this global crisis, antimicrobial peptides are considered promising alternatives to counter bacterial infections with multi-drug resistant bacteria. The cathelicidins comprise a well-studied class of AMPs whose members have been used as model molecules for sequence modifications, aiming at enhanced biological activities and stability, along with reduced toxic effects on mammalian cells. Here, we describe the antimicrobial activities, modes of action and structural characterization of two novel cathelicidin-like peptides, named BotrAMP14 and CrotAMP14, which were re-designed from snake batroxicidin and crotalicidin, respectively. BotrAMP14 and CrotAMP14 showed broad-spectrum antibacterial activity against susceptible microorganisms and clinical isolates with minimal inhibitory concentrations ranging from 2-35.1 μM. Moreover, both peptides had low cytotoxicity against Caco-2 cells in vitro. In addition, in vivo toxicity against Galleria mellonella moth larvae revealed that both peptides led to>76% larval survival after 144 h. Microscopy studies suggest that BotrAMP14 and CrotAMP14 destabilize E. coli membranes. Furthermore, circular dichroism and molecular dynamics simulations indicate that, in a membrane-like environment, both peptides adopt α-helical structures that interact with bilayer phospholipids through hydrogen bonds and electrostatic interaction. Thus, we concluded that BotrAMP14 and CrotAMP14 are helical membrane active peptides, with similar antibacterial properties but lower cytotoxicity than the larger parent peptides batroxicidin and crotalicidin, having advantages for drug development strategies

A biological question and a balanced (orthogonal) design: the ingredients to efficiently analyze two-color microarrays with Confirmatory Factor Analysis

BACKGROUND: Factor analysis (FA) has been widely applied in microarray studies as a data-reduction-tool without any a-priori assumption regarding associations between observed data and latent structure (Exploratory Factor Analysis). A disadvantage is that the representation of data in a reduced set of dimensions can be difficult to interpret, as biological contrasts do not necessarily coincide with single dimensions. However, FA can also be applied as an instrument to confirm what is expected on the basis of pre-established hypotheses (Confirmatory Factor Analysis, CFA). We show that with a hypothesis incorporated in a balanced (orthogonal) design, including 'SelfSelf' hybridizations, dye swaps and independent replications, FA can be used to identify the latent factors underlying the correlation structure among the observed two-color microarray data. An orthogonal design will reflect the principal components associated with each experimental factor. We applied CFA to a microarray study performed to investigate cisplatin resistance in four ovarian cancer cell lines, which only differ in their degree of cisplatin resistance. RESULTS: Two latent factors, coinciding with principal components, representing the differences in cisplatin resistance between the four ovarian cancer cell lines were easily identified. From these two factors 315 genes associated with cisplatin resistance were selected, 199 genes from the first factor (False Discovery Rate (FDR): 19%) and 152 (FDR: 24%) from the second factor, while both gene sets shared 36. The differential expression of 16 genes was validated with reverse transcription-polymerase chain reaction. CONCLUSION: Our results show that FA is an efficient method to analyze two-color microarray data provided that there is a pre-defined hypothesis reflected in an orthogonal design

A Machine Learning Approach to Measure and Monitor Physical Activity in Children to Help Fight Overweight and Obesity

Physical Activity is important for maintaining healthy lifestyles. Recommendations for physical activity levels are issued by most governments as part of public health measures. As such, reliable measurement of physical activity for regulatory purposes is vital. This has lead research to explore standards for achieving this using wearable technology and artificial neural networks that produce classifications for specific physical activity events. Applied from a very early age, the ubiquitous capture of physical activity data using mobile and wearable technology may help us to understand how we can combat childhood obesity and the impact that this has in later life. A supervised machine learning approach is adopted in this paper that utilizes data obtained from accelerometer sensors worn by children in free-living environments. The paper presents a set of activities and features suitable for measuring physical activity and evaluates the use of a Multilayer Perceptron neural network to classify physical activities by activity type. A rigorous reproducible data science methodology is presented for subsequent use in physical activity research. Our results show that it was possible to obtain an overall accuracy of 96 % with 95 % for sensitivity, 99 % for specificity and a kappa value of 94 % when three and four feature combinations were used