Editorial for 'New talent' collection: introducing New Talent in chemistry and material science.

We introduce 14 articles published as part of the 'New talent' special collection of invited articles to showcase some of the exciting work being funded by the Royal Society. As Royal Society University Research Fellows or Dorothy Hodgkin Fellowship holders, the contributors to this collection are rising stars in their areas of research. This collection also illustrates the close collaboration between Royal Society Open Science and the Royal Society of Chemistry. The collection spans the range of the chemical and material sciences, reflecting the breadth of research areas receiving Royal Society grant support

Light scattering and optical diffusion from willemite spherulites

Willemite is a zinc silicate mineral used in modern day pottery as a decorative feature within glazes. It is produced by controlled heat treatment of zinc oxide-containing ceramic glazes. The heat-treated glazes devitrify, producing thin nanoscale needle-like willemite crystals growing in spherulitic morphologies through branching of the needles. We show here that this resulting morphology of willemite crystals in an inorganic glass matrix has a previously unreported strong interaction with light, displaying remarkable optical diffraction patterns. Thin sections of such spherulites act as optical diffusers, enabling light beams to be spread up to 160° in width. Analysis of the interaction between the willemite spherulites and light suggests that the high density of willemite crystals in the spherulites and the length scales associated with both the thickness of the needles and the spacings between branches are together responsible for this optical diffusion behaviour.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.optmat.2015.12.02

Panarctic lakes exerted a small positive feedback on early Holocene warming due to deglacial release of methane

Climate-driven permafrost thaw can release ancient carbon to the atmosphere, begetting further warming in a positive feedback loop. Polar ice core data and young radiocarbon ages of dissolved methane in thermokarst lakes have challenged the importance of this feedback, but field studies did not adequately account for older methane released from permafrost through bubbling. We synthesized panarctic isotope and emissions datasets to derive integrated ages of panarctic lake methane fluxes. Methane age in modern thermokarst lakes (3132 ± 731 years before present) reflects remobilization of ancient carbon. Thermokarst-lake methane emissions fit within the constraints imposed by polar ice core data. Younger, albeit ultimately larger sources of methane from glacial lakes, estimated here, lagged those from thermokarst lakes. Our results imply that panarctic lake methane release was a small positive feedback to climate warming, comprising up to 17% of total northern hemisphere sources during the deglacial period

Medical causes of admissions to hospital among adults in Africa: a systematic review.

BACKGROUND: Despite the publication of several studies on the subject, there is significant uncertainty regarding the burden of disease among adults in sub-Saharan Africa (sSA). OBJECTIVES: To describe the breadth of available data regarding causes of admission to hospital, to systematically analyze the methodological quality of these studies, and to provide recommendations for future research. DESIGN: We performed a systematic online and hand-based search for articles describing patterns of medical illnesses in patients admitted to hospitals in sSA between 1950 and 2010. Diseases were grouped into bodily systems using International Classification of Disease (ICD) guidelines. We compared the proportions of admissions and deaths by diagnostic category using χ2. RESULTS: Thirty articles, describing 86,307 admissions and 9,695 deaths, met the inclusion criteria. The leading causes of admission were infectious and parasitic diseases (19.8%, 95% confidence interval [CI] 19.6-20.1), respiratory (16.2%, 95% CI 16.0-16.5) and circulatory (11.3%, 95% CI 11.1-11.5) illnesses. The leading causes of death were infectious and parasitic (17.1%, 95% CI 16.4-17.9), circulatory (16%, 95% CI 15.3-16.8) and digestive (16.2%, 95% CI 15.4-16.9). Circulatory diseases increased from 3.9% of all admissions in 1950-59 to 19.9% in 2000-2010 (RR 5.1, 95% CI 4.5-5.8, test for trend p<0.00005). The most prevalent methodological deficiencies, present in two-thirds of studies, were failures to use standardized case definitions and ICD guidelines for classifying illnesses. CONCLUSIONS: Cardiovascular and infectious diseases are currently the leading causes of admissions and in-hospital deaths in sSA. Methodological deficiencies have limited the usefulness of previous studies in defining national patterns of disease in adults. As African countries pass through demographic and health transition, they need to significantly invest in clinical research capacity to provide an accurate description of the disease burden among adults for public health policy

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion

Risk factors for race-day fatality in flat racing Thoroughbreds in Great Britain (2000 to 2013)

A key focus of the racing industry is to reduce the number of race-day events where horses die suddenly or are euthanased due to catastrophic injury. The objective of this study was therefore to determine risk factors for race-day fatalities in Thoroughbred racehorses, using a cohort of all horses participating in flat racing in Great Britain between 2000 and 2013. Horse-, race- and course-level data were collected and combined with all race-day fatalities, recorded by racecourse veterinarians in a central database. Associations between exposure variables and fatality were assessed using logistic regression analyses for (1) all starts in the dataset and (2) starts made on turf surfaces only. There were 806,764 starts in total, of which 548,571 were on turf surfaces. A total of 610 fatalities were recorded; 377 (61.8%) on turf. In both regression models, increased firmness of the going, increasing racing distance, increasing average horse performance, first year of racing and wearing eye cover for the first time all increased the odds of fatality. Generally, the odds of fatality also increased with increasing horse age whereas increasing number of previous starts reduced fatality odds. In the ‘all starts’ model, horses racing in an auction race were at 1.46 (95% confidence interval (CI) 1.06–2.01) times the odds of fatality compared with horses not racing in this race type. In the turf starts model, horses racing in Group 1 races were at 3.19 (95% CI 1.71–5.93) times the odds of fatality compared with horses not racing in this race type. Identification of novel risk factors including wearing eye cover and race type will help to inform strategies to further reduce the rate of fatality in flat racing horses, enhancing horse and jockey welfare and safety

Preoperative Rectal Cancer Management: Wide International Practice Makes Outcome Comparison Challenging: Reply

In a letter to the editor Dr. Hottenrott provides valuable comments on our survey describing international preoperative rectal cancer management. In our opinion, three key messages are derived from our survey: First, most surgeons agree to neoadjuvant treatment when there is an increased risk of finding histologically positive circumferential margins. In addition, we found more than 40 other indications for neoadjuvant treatment (see our Table 4). This emphasizes the need for an international agreement, as different indications for neoadjuvant treatment will select noncomparable groups of patients in outcome studies. Second, we have shown (see our Table 6) that multidisciplinary team (MDT) meetings significantly influence several important decisions in preoperative rectal cancer management. Interestingly, centers with regular MDT have a higher rate of using magnetic resonance imaging (MRI) (Odds Ratio [OR] = 3.62) and consider a threatened circumferential resection margin (CRM) as indication for neoadjuvant treatment (OR = 5.67). We believe that MDT improves preoperative management of rectal cancer by increasing adherence to national guidelines. Similar discussions in international rectal cancer societies are needed aiming towards an international consensus statement. Finally, our survey revealed sparse use (35% of all cases) of MRI. The goal for the radiologic examination in rectal cancer is to explore the tumor’s relation to nearby anatomical structures. This evaluation will conclude with TNM staging, important for chemoradiotheraphy, surgical treatment, and prognosis. Magnetic resonance imaging has a central role in this evaluation and should be the first choice radiologic modality. Not only is MRI crucial in detection of TNM stage but also plays a central role in determination of the tumor’s distance to the mesorectal fascia and the CRM. Magnetic resonance imaging has moderate sensitivity on T1 and T2 tumors, and should be supplemented with rectal ultrasound

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Mental health literacy as a function of remoteness of residence: an Australian national study

<p>Abstract</p> <p>Background</p> <p>Although there have been many population studies of mental health literacy, little is known about the mental health literacy of people who reside in rural areas. This study sought to determine the impact of remoteness on public knowledge of depression and schizophrenia.</p> <p>Methods</p> <p>The mental health literacy of residents of major cities, inner regional, and outer-remote (including outer regional, remote, and very remote) regions were compared using data from a 2003–04 Australian national survey of the mental health literacy of 3998 adults. Measures included the perceived helpfulness of a range of professionals, non-professionals and interventions, and the causes, prognosis, and outcomes after treatment for four case vignettes describing depression, depression with suicidal ideation, early schizophrenia and chronic schizophrenia. Participant awareness of Australia's national depression initiative and depression in the media, their symptoms of depression and exposure to the conditions depicted in the vignettes were also compared.</p> <p>Results</p> <p>Mental health literacy was similar across remoteness categories. However, inner regional residents showed superior identification of the disorders depicted in the suicidal ideation and chronic schizophrenia vignettes. They were also more likely to report having heard of Australia's national depression health promotion campaign. Conversely, they were less likely than major city residents to rate the evidence-based treatment of psychotherapy helpful for depression. Both inner regional and outer-remote residents were less likely to rate psychologists as helpful for depression alone. The rural groups were more likely to rate the non-evidence based interventions of drinking and painkillers as helpful for a depression vignette. In addition, outer-remote residents were more likely to identify the evidence based treatment of antipsychotics as harmful for early schizophrenia and less likely to endorse psychiatrists, psychologists, social workers and general practitioners as helpful for the condition.</p> <p>Conclusion</p> <p>Mental health awareness campaigns in rural and remote regions may be most appropriately focused on communicating which interventions are effective for depression and schizophrenia and which mental health and other professionals are trained in the best-practice delivery and management of these. There is also a need to communicate to rural residents that alcohol and pain relievers are not an effective solution for depression.</p

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups