Thyroid FNAC cytology: can we do it better?

This article reviews recent developments in thyroid fine needle aspiration cytology (FNAC). While thyroid nodules are common, carcinoma is comparatively rare. Although histological assessment is used in most studies as the benchmark, the differential diagnosis on cytology or histology is not always reproducible. The literature shows wide variations in criteria for inadequate thyroid FNAC and study inclusion or exclusion criteria. In-clinic assessment of specimen adequacy and in-clinic reporting of thyroid FNAC has become popular although the costs and resource implications of in-clinic thyroid FNAC assessment and reporting are substantial. Many centres continue to use conventional techniques although liquid-based cytology and ultrasound-guided FNAC are gaining in popularity. Standardized categorical systems for FNAC reporting can make results easier to understand for clinicians and give clear indications for therapeutic action. Multidisciplinary case review is also essential, especially when there is diagnostic uncertainty. While currently of limited use, molecular pathology testing holds out some promise for the future.     

Measuring bone mass in children: can we really do it?

Bone densitometry is used to assess skeletal health in clinical and research settings, with the goal of achieving reproducible measurements of bone mass that help to identify individuals predisposed to fracture. The search is now on for better methods of capturing additional factors that contribute to bone strength, including bone size, geometry, microarchitecture, and turnover rates. This has proved particularly challenging in growing children, whose bones continually change in size, shape, and mass. Dual energy X-ray absorptiometry is the preferred method for measuring bone mass in children, but the technique has several limitations, and interpreting the findings can be problematic. Peripheral quantitative computed tomography is a promising method for assessing bone mass and other indices correlating with bone strength, but a lack of precision and paediatric norms currently restricts its clinical utility. Although bone mineral density is predictive of future fracture risk in adults, the evidence in children is less conclusive, and a diagnosis of osteoporosis in a child should not be made on densitometric findings alone. Developing a clearer understanding of how measures of bone mass and strength correlate with bone fracture in children will help target preventive strategies for those in greatest need.     

How can we bring together empiricists and modellers in functional biodiversity research?

Improving our understanding of biodiversity and ecosystem functioning and our capacity to inform ecosystem management requires an integrated framework for functional biodiversity research (FBR). However, adequate integration among empirical approaches (monitoring and experimental) and modelling has rarely been achieved in FBR. We offer an appraisal of the issues involved and chart a course towards enhanced integration. A major element of this path is the joint orientation towards the continuous refinement of a theoretical framework for FBR that links theory testing and generalization with applied research oriented towards the conservation of biodiversity and ecosystem functioning. We further emphasize existing decision-making frameworks as suitable instruments to practically merge these different aims of FBR and bring them into application. This integrated framework requires joint research planning, and should improve communication and stimulate collaboration between modellers and empiricists, thereby overcoming existing reservations and prejudices. The implementation of this integrative research agenda for FBR requires an adaptation in most national and international funding schemes in order to accommodate such joint teams and their more complex structures and data needs.     

When less can be better: How can we make genomic selection more cost-effective and accurate in barley?

Key message

We were able to obtain good prediction accuracy in genomic selection with ~?2000 GBS-derived SNPs. SNPs in genic regions did not improve prediction accuracy compared to SNPs in intergenic regions.

Abstract

Since genotyping can represent an important cost in genomic selection, it is important to minimize it without compromising the accuracy of predictions. The objectives of the present study were to explore how a decrease in the unit cost of genotyping impacted: (1) the number of single nucleotide polymorphism (SNP) markers; (2) the accuracy of the resulting genotypic data; (3) the extent of coverage on both physical and genetic maps; and (4) the prediction accuracy (PA) for six important traits in barley. Variations on the genotyping by sequencing protocol were used to generate 16 SNP sets ranging from ~?500 to ~?35,000 SNPs. The accuracy of SNP genotypes fluctuated between 95 and 99%. Marker distribution on the physical map was highly skewed toward the terminal regions, whereas a fairly uniform coverage of the genetic map was achieved with all but the smallest set of SNPs. We estimated the PA using three statistical models capturing (or not) the epistatic effect; the one modeling both additivity and epistasis was selected as the best model. The PA obtained with the different SNP sets was measured and found to remain stable, except with the smallest set, where a significant decrease was observed. Finally, we examined if the localization of SNP loci (genic vs. intergenic) affected the PA. No gain in PA was observed using SNPs located in genic regions. In summary, we found that there is considerable scope for decreasing the cost of genotyping in barley (to capture ~?2000 SNPs) without loss of PA.

     

The molecular biology of recombination in Mycobacteria: what do we know and how can we use it?

Recombination is a ubiquitous genetic process which results in the exchange of DNA between two substrates. Homologous recombination occurs between DNA species with identical sequence whereas illegitimate recombination can occur between DNA with very little or no homology. Site-specific recombination is often used by temperate phages to stably integrate into bacterial chromosomes. Characterisation of the mechanisms of recombination in mycobacteria has mainly focussed on RecA-dependent homologous recombination and phage-directed site-specific recombination. In contrast the high frequency of illegitimate recombination in slow-growing mycobacteria has not been explained. The role of DNA repair in dormancy and infection have not yet been fully established, but early work suggests that RecA-mediated pathways are not required for virulence. All three recombination mechanisms have been utilised in developing genetic techniques for the analysis of the biology and pathogenesis of mycobacteria. A recently developed method for studying essential genes will generate further insights into the biology of these important organisms.     

Regeneration: if they can do it,why can't we?

The therapeutic potential of stem cells and nuclear cloning has led to renewed interest in classical models of regeneration. This longstanding problem is undergoing a renaissance spurred by the availability of new techniques that finally allow analysis on the cellular and molecular level.     

Examining the developing bone: What do we measure and how do we do it?

The clinical tools available to evaluate bone development in children are often ambiguous, and difficult to interpret. Unfortunately bone densitometry methods (i.e., dual energy X-ray absorptiometry, DXA) which have a relatively straightforward application in adult osteoporosis, are far more difficult to evaluate in the growing skeleton. Even with adequate "adjustment" for bone size or maturity, bone "density" (areal or volumetric) alone often gives an inaccurate assessment of bone strength--especially in children. Ideally, we would like to measure both material and geometric properties of bone to accurately estimate "strength". Mechanically meaningful measures of bone geometry (bone cross-sectional area, cortical thickness) and estimates of bending strength (section modulus, or SSI) are available with non-invasive techniques such as (p)QCT and some DXA software. With new technology it might be possible to also measure bone material properties, which will be especially important in some pediatric disorders. In children, we also need to know something about the loads imposed on a child's bone and consider not only absolute bone strength, but also the strength of bone relative to the physiologic loads. Interpreting bone strength in light of the loads imposed (particularly muscle force) is critical for an accurate diagnosis of the developing bone.     

Threat status in butterflies and its ecological correlates: how far can we generalize?

It would be very useful for conservation biologists to be able to predict threat status from ecological characteristics of species, and past studies have shown promising results. Regarding one important threat indicator taxon, the butterflies, results from a study on Finnish species by Kotiaho et al. (Proc Natl Acad Sci USA 102:1963–1967, 2005), suggested that threatened butterflies on average have narrower niches, more restricted distributions of the larval host plants, poorer dispersal abilities and shorter flight periods. However, this study did not control for phylogenetic relatedness of species. To examine the effects of phylogenetic control, and to see how far it is possible to generalize from specific investigations, we compared the ecological characteristics of threatened and non-threatened butterfly species at two different geographical scales: Sweden and Europe. Our results illustrate the difficulties of generalizing between sites, geographical scales, scoring methods, and phylogenetic versus non-phylogenetic analyses. Controlling for phylogeny is shown to be essential. The most robust result is that threatened species have narrower habitat ranges at the local scale.     

Mechanosensitive channels: what can they do and how do they do it?

While mechanobiological processes employ diverse mechanisms, at their heart are force-induced perturbations in the structure and dynamics of molecules capable of triggering subsequent events. Among the best characterized force-sensing systems are bacterial mechanosensitive channels. These channels reflect an intimate coupling of protein conformation with the mechanics of the surrounding membrane; the membrane serves as an adaptable sensor that responds to an input of applied force and converts it into an output signal, interpreted for the cell by mechanosensitive channels. The cell can exploit this information in a number of ways: ensuring cellular viability in the presence of osmotic stress and perhaps also serving as a signal transducer for membrane tension or other functions. This review focuses on the bacterial mechanosensitive channels of large (MscL) and small (MscS) conductance and their eukaryotic homologs, with an emphasis on the outstanding issues surrounding the function and mechanism of this fascinating class of molecules.     

How do we Measure the Environment? Linking Intertidal Thermal Physiology and Ecology Through Biophysics

Recent advances in quantifying biochemical and cellular-levelresponses to thermal stress have facilitated a new explorationof the role of climate and climate change in driving intertidalcommunity and population ecology. To fruitfully connect thesedisciplines, we first need to understand what the body temperaturesof intertidal organisms are under field conditions, and howthey change in space and time. Newly available data logger technologymakes such an exploration possible, but several potential pitfallsmust be avoided. Body temperature during aerial exposure isdriven by multiple, interacting climatic factors, and extremesduring low tide far exceed those during submersion. Moreover,because of effects of body size and morphology, two organismsexposed to identical climatic conditions can display very differentbody temperatures, which can also be substantially differentfrom the temperature of the surrounding air. These same factorsdrive the temperature recorded by data loggers, and one loggertype is unlikely to serve as an effective proxy for all organismsat a site. Here I describe the difficulties involved in quantifyingpatterns of body temperature in intertidal organisms, and explorethe implications of this complexity for intertidal physiologicalecology. I do so using data from temperature loggers designedto mimic the thermal characteristics of the mussel Mytilus californianus,and deployed at multiple sites along the West Coast of the UnitedStates. Results indicate a highly intricate pattern of thermalstress, where the interaction of climate with the dynamics ofthe tidal cycle determines the timing and magnitude of temperatureextremes, creating a unique "thermal signal" at each site.     

Turbidity in the Thames Estuary: How turbid do we expect it to be?

A previously derived method (the tidal length—mean spring tidal range, TL-MSTR diagram) is used to predict the estuarine turbidity maximum (ETM) concentration and the residence time of the Thames Estuary. The predicted and observed residence time is 2 months. The predicted, depth-averaged ETM is 2.5 g l⁻¹ of suspended particulate matter (SPM) at spring tides, which is much higher than that observed from surface sampling (<0.5 g l⁻¹) and that simulated by recent models (approx. 0.6 g l⁻¹), but is consistent with spring-tide concentrations measured throughout the water column over a tidal cycle. The observed locations of the surface 1-isohaline and 5-isohaline exhibit strong relationships with the logarithm of freshwater runoff. The observed ETM exhibits statistically significant relationships both with tidal range and the logarithm of runoff, and is generally located between the Millennium Dome and the Woolwich Reach. The apparent over-prediction of SPM afforded by the TL-MSTR diagram is unsurprising considering the removal of fine sediment by dredging and the removal of fine-sediment storage areas by embanking.     

Lipids in cell biology: how can we understand them better?

Lipids are a major class of biological molecules and play many key roles in different processes. The diversity of lipids is on the same order of magnitude as that of proteins: cells express tens of thousands of different lipids and hundreds of proteins to regulate their metabolism and transport. Despite their clear importance and essential functions, lipids have not been as well studied as proteins. We discuss here some of the reasons why it has been challenging to study lipids and outline technological developments that are allowing us to begin lifting lipids out of their “Cinderella” status. We focus on recent advances in lipid identification, visualization, and investigation of their biophysics and perturbations and suggest that the field has sufficiently advanced to encourage broader investigation into these intriguing molecules.Lipids are fundamental building blocks of all cells and play many important and varied roles. They are key components of the plasma membrane and other cellular compartments, including the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, and trafficking vesicles such as endosomes and lysosomes. The lipid composition of different organelles, cell types, and ultimately tissues can vary substantially, suggesting that different lipids are required for different functions (Saghatelian et al., 2006 ; Klose et al., 2013 ). Mammalian cells express tens of thousands of different lipid species and use hundreds of proteins to synthesize, metabolize, and transport them. Although the complexity and diversity of lipids approach those of proteins, we have a much poorer understanding of their functions, making lipids in many ways the “Cinderellas” of cell biology. We discuss here recent advances, and challenges, in investigating how these molecules contribute to the many biological processes in which they participate.Like proteins, lipids can have structural (e.g., by stabilizing different membrane curvatures) or signaling roles. Posttranslational lipidation of proteins (e.g., palmitoylation or farnesylation) and carbohydrate-linked lipids (glycolipids) are also important examples of cellular lipid pools. It is clear that higher-order organization is key to most lipid functions, and they are believed to assemble into signaling platforms that contain both lipids and proteins (Kusumi et al., 2012 ). Some lipid microdomains are termed lipid rafts, and much ongoing effort is being focused on defining their parameters (Simons and Sampaio, 2011 ; Suzuki et al., 2012 ; Klotzsch and Schutz, 2013 ). Because of this focus on lipid rafts, we have a better understanding of the properties of proposed raft lipids (e.g., sphingomyelins and cholesterol) than of many other lipid species. Much of what we know about lipids has come from studying synthetic membranes with specific lipid compositions. Although model membranes usually consist of very few (<10) lipid species, they have been useful for understanding the biophysical properties of lipids. At the other end of the spectrum, lipids have been implicated in various diseases, with cholesterol metabolism being a prominent example. We are now getting to a point at which we can address the roles of lipids in the middle of the spectrum—in cells.     

Predictors and barriers to breastfeeding in north of Jordan: could we do better?

Background

Despite the ongoing recommendations for breastfeeding, we continue to see a decrease in exclusive breastfeeding among Jordanian women during infant follow up visits at the pediatric outpatient clinic. The purpose of our study is to determine the prevalence, predictors and barriers to exclusive breastfeeding in north of Jordan.

Methods

We conducted a cross-sectional survey involving mothers with infants six to twelve months old, at two hospitals in Irbid city in north of Jordan, between December 2016 and March 2017. Questions included demographics, feeding pattern, and reasons for non-exclusive breastfeeding.

Results

Five hundred women were included. Twenty four percent of women were employed and 87% initiated breastfeeding within three hours of birth. The proportion of women with any breastfeeding and exclusive breastfeeding at six months was 76 and 33%. After multivariate logistic regression analysis, predictors of exclusive breastfeeding at six months include the mother’s previous experience (Adjusted Odds Ratio [AOR] 7.9, 95% CI 4.69, 13.36) and multiparity (AOR 2.26, 95% CI 1.2, 4.28), while barriers include maternal employment (AOR 0.4, 95% CI 0.22,0.72), Cesarean delivery (AOR 0.55, 95% CI 0.35, 0.86) and infant’s hospitalization (AOR 0.44, 95% CI 0.23,0.82). Inadequate breastmilk supply and short maternity leave were the main reported reasons for non-exclusive breastfeeding.

Conclusions

In north of Jordan, the majority of women initiate breastfeeding, half practice exclusive breastfeeding after birth while one third continue for six months, particularly those with previous experience. Cesarean delivery and infant’s hospitalization, together with maternal employment are among the main barriers. Implementing educational programs and lactation consultant counselling together with work environment support, should be helpful to improve the breastfeeding practice among Jordanian women.

     

Breastfeeding in public: “You can do it?”

On a regular basis there is an outcry about a mother who has been told to cover up or move away from a public area while she is breastfeeding. Mothers should feel free to breastfeed whenever they need to. However, the increasing market for “nursing covers” to hide the breast while feeding is evidence of changing perceptions. Discomfort with the idea of breastfeeding in public has been cited as a reason for some women choosing not to initiate breastfeeding or planning a shorter duration of breastfeeding. Other women are choosing to express and bottle-feed their expressed milk when they are in public. In many cultures today there is a conflict between the concept of breast milk being pure (like tears), and contaminated or “dirty” (like genital secretions or vomit). In these settings the female breast may be considered primarily a sexual organ, and therefore a private part of the body, which needs to be invisible in the public arena. In order to increase breastfeeding initiation and duration and to reduce health inequities breastfeeding needs to be more visible. Let’s strive together to make breastfeeding in public unremarkable.     

Nitrogen limitation on land and in the sea: How can it occur?

The widespread occurrence of nitrogen limitation to net primary production in terrestrial and marine ecosystems is something of a puzzle; it would seem that nitrogen fixers should have a substantial competitive advantage wherever nitrogen is limiting, and that their activity in turn should reverse limitation. Nevertheless, there is substantial evidence that nitrogen limits net primary production much of the time in most terrestrial biomes and many marine ecosystems. We examine both how the biogeochemistry of the nitrogen cycle could cause limitation to develop, and how nitrogen limitation could persist as a consequence of processes that prevent or reduce nitrogen fixation. Biogeochemical mechansism that favor nitrogen limitation include:

the substantial mobility of nitrogen across ecosystem boundaries, which favors nitogen limitation in the “source” ecosystem — especially where denitrification is important in sediments and soils, or in terrestrial ecosystems where fire is frequent;

differences in the biochemistry of nitrogen as opposed to phosphorus (with detrital N mostly carbon-bonded and detrital P mostly ester-bonded), which favor the development of nitrogen limitation where decomposition is slow, and allow the development of a positive feedback from nitrogen limitation to producers, to reduced decomposition of their detritus, and on to reduced nitrogen availability; and

other more specialized, but perhaps no less important, processes.

A number of mechanisms could keep nitrogen fixation from reversing nitrogen limitation. These include:

energetic constraints on the colonization or activity of nitrogen fixers;

limitation of nitrogen fixers or fixation by another nutrient (phosphorus, molybdenum, or iron) — which would then represent the ultimate factor limiting net primary production;

other physical and ecological mechanisms.

The possible importance of these and other processes is discussed for a wide range of terrestrial, freshwater, and marine ecosystems.     

The principles and practice of human evolution research: Are we asking questions that can be answered?

The research agenda of paleoanthropology involves many topics and methodologies. Fossil specimens are allocated to species, and those species are assigned to the hominin clade. After that we want to know how they are related to each other, what they ate, how much they weighed, how smart they were, etc. We also want to know about the origin of particular attributes of hominins, such as our delayed growth and development, bipedalism, and language. The data available to answer these complex questions are confounded by fragmentary fossil specimens, small sample sizes, limited opportunities for controlled experimentation, and the inherent limitations of historical data. Also, because many traits are effectively unique to hominins, even observational comparative studies are inevitably limited in what they can tell us, if not impossible to conduct. We explore how these limitations should, but often do not, constrain the questions that paleoanthropologists should attempt to answer.