Five authors reply

We read with interest the comments offered by Drs. Hughes and Bradley (1) on our systematic review (2). Four single nucleotide polymorphisms (SNPs), rs9332739 and rs547154 in the complement component 2 gene (C2) and rs4151667 and rs641153 in the complement factor B gene (CFB), were pooled. Hughes and Bradley point out that we omitted the most common variant, rs12614. In fact, rs12614 is in high linkage disequilibrium (LD) with rs641153, which was included, and the major allele of both of these SNPs is in the range of 90% (population code, CEU, in the International HapMap Project (http://hapmap.ncbi.nlm.nih.gov/)). Moreover, our review was initiated in September 2010, at which point only 4 studies had published associations with rs12614, whereas 14 studies (n = 11,378) were available for rs641153. While it is true that both SNPs are better analyzed as a haplotype, these data were simply not available for pooling.
Hughes and Bradley also point out that we obtained and pooled new data that were not previously published. While it is recommended that contact with authors be completed as part of a comprehensive meta-analysis, we acknowledge that these additional data were not previously published and peer reviewed and, hence, do not have the same level of transparency. However, given that sample collections often increase over time and that the instrumentation for genotyping is continually improving, we thought that it would be advantageous to use the most recent information; this is a subjective decision.
We also agree that the allele frequencies given by Kaur et al. (3) were exactly opposite to those expected and were suggestive of strand flipping. However, we specifically queried this with the lead author on 2 separate occasions and were assured it was not.
Hughes and Bradley do make an interesting suggestion that SNPs in high LD should be used as a gauge of genotyping quality in HuGE reviews. This is an interesting idea but difficult to put into practice as the r2 parameter they propose as a measure of LD has some unusual properties. Although r2 is a measure of LD, it is also linked to the allele frequency; even small differences in allele frequencies between 2 linked SNPs can reduce the r2 dramatically. Wray (4) explored these effects and found that, at a baseline allele frequency of 10%, even a difference in allele frequency between 2 SNPs as small as 2% can drop the r2 value below 0.8. This degree of allele frequency difference is consistent with what could be expected for sampling error. Furthermore, when we look at 2 linked dialleleic SNPs, giving 4 possible haplotypes, the absence of 1 haplotype dramatically reduces r2, despite the 2 loci being in high LD as measured by D'. In fact, this is the situation for rs12614 and rs641153, where the low frequency of 1 haplotype means that the r2 is 0.01 but the D' is 1.
Hughes and Bradley also suggest consideration of genotype call rate restrictions as an inclusion criterion for metaanalysis. This would be more appropriate when focusing on genetic variants per se, as considered within the context of a genome-wide association study or other specific genetic analysis where large numbers of SNPs are evaluated (5).
The concerns raised by Hughes and Bradley reflect the limited ability of a meta-analysis based on summary data to tease out inconsistencies best identified at the individual level. We agree that SNPs in LD should be evaluated, but this will not necessarily be straightforward. A move to make genetic data sets publicly available, as in the Database of Genotypes and Phenotypes (http://www.ncbi.nlm.nih.gov/ gap), is a step in the right direction for greater transparency.

Energy expenditure during activity in the American lobster Homarus americanus:Correlations with body acceleration

How animals manage time and expend energy has implications for survivorship. Being able to measure key metabolic costs of animals under natural conditions is therefore an important tool in behavioral ecology. One method for estimating activity-specific metabolic rate is via derived measures of acceleration, often 'overall dynamic body acceleration' (ODBA), recorded by an instrumented acceleration logger. ODBA has been shown to correlate well with rate of oxygen consumption (V ?o) in a range of species during activity in the laboratory. This study devised a method for attaching acceleration loggers to decapod crustaceans and then correlated ODBA against concurrent respirometry readings to assess accelerometry as a proxy for activity-specific energy expenditure in a model species, the American lobster Homarus americanus. Where the instrumented animals exhibited a sufficient range of activity levels, positive linear relationships were found between V ?o and ODBA over 20min periods at a range of ambient temperatures (6, 13 and 20°C). Mixed effect linear models based on these data and morphometrics provided reasonably strong predictive power for estimating activity-specific V ?o from ODBA. These V ?o-ODBA calibrations demonstrate the potential of accelerometry as an effective predictor of behavior-specific metabolic rate of crustaceans in the wild during periods of activity. © 2013 Elsevier Inc.

Consensus in organizations:Hunting for the social choice conundrum in APA elections

According to the axiomatic literature on consensus methods, the best collective choice by one method of preference aggregation can easily be the worst by another. Are award committees, electorates, managers, online retailers, and web-based recommender systems stuck with an impossibility of rational preference aggregation? We investigate this social choice conundrum for seven social choice methods: Condorcet, Borda, Plurality, Antiplurality, the Single Transferable Vote, Coombs, and Plurality Runoff. We rely on Monte Carlo simulations for theoretical results and on twelve ballot datasets from American Psychological Association (APA) presidential elections for empirical results. Each of these elections provides partial rankings of five candidates from about 13,000 to about 20,000 voters. APA preferences are neither domain-restricted nor generated by an Impartial Culture. We find virtually no trace of a Condorcet paradox. In direct contrast with the classical social choice conundrum, competing consensus methods agree remarkably well, especially on the overall best and worst options. The agreement is also robust under perturbations of the preference prole via resampling, even in relatively small pseudosamples. We also explore prescriptive implications of our findings.

AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog, Agalychnis callidryas

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50 = 9.3 μM). The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L) Escherichia coli (MIC = 512 mg/L), and Candida albicans (128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

Trading Activity in Options and Stock Around Price-Sensitive News Announcements

This study investigates the trading activity in options and stock markets around informed events with extreme daily stock price movements. We find that informed agents are more likely to trade options prior to negative news and stocks ahead of positive news. We also show that optioned stocks overreact to the arrival of negative news, but react efficiently to positive news. However, the overreaction patterns are unique to the subsample of stocks with the lowest pre-event abnormal option/stock volume ratio (O/S). This finding suggests that the incremental benefit of option listing is related to the level of option trading activity, over and beyond the presence of an options market on the firm's stock. Finally, we find that the pre-event abnormal O/S is a better predictor of stock price patterns following a negative shock than is the pre-event O/S, implying that the former may contain more information about the future value of stocks than the latter.

Due North? Do American Theories of Legislative Committees Apply to Canada?

Several theories of legislative organisation have been proposed to explain committee selection in American legislatures, but do these theories travel outside the United States? This paper tests whether these theories apply to data from the Canadian House of Commons. It was found that the distributive and partisan models of legislative organisation explain committee composition in Canada. In many cases, committees in the House of Commons are made up of preference outliers. As predicted by partisan models, it was also found that the governing party stacks committees with its members, but this is conditional upon the strength of the governing party.

Periodontal Manifestations of Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE) Syndrome in an 11 Year Old Patient

Introduction: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) is an auto inflammatory syndrome caused by an autosomal recessive gene mutation. This very rare syndrome has been reported in only 14 patients worldwide. A number of clinical signs have been reported including joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced childhood lipodystrophy. Further symptoms include recurrent fevers, purpuric skin lesions, periorbital erythema and failure to thrive. This is the first reported case of periodontal manifestations associated with CANDLE syndrome. 
Case Presentation: An 11 year old boy was referred to Cork University Dental School and Hospital with evidence of severe periodontal destruction. The patient’s medical condition was managed in Great Ormond Street Children’s Hospital, London. The patient’s dental management included initial treatment to remove teeth of hopeless prognosis followed by prosthodontic rehabilitation using removable partial dentures. This was followed by further non-surgical periodontal treatment and maintenance. In the long term, the potential definitive restorative options, including dental implants, will be evaluated in discussion with the patient’s medical team.
Conclusion: Periodontitis as a manifestation of systemic disease is one of seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system. A number of systemic diseases have been associated with advanced periodontal destruction including Diabetes Mellitus, Leukaemia and Papillon-Lefevre Syndrome. In the case described, treatment necessitated a multidisciplinary approach with input from medical and dental specialities for a young patient with severe periodontal destruction associated with CANDLE syndrome.

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

Despite significant advances in treatment strategies targeting the underlying defect in cystic fibrosis (CF), airway infection remains an important cause of lung disease. In this two-part series, we review recent evidence related to the complexity of CF airway infection, explore data suggesting the relevance of individual microbial species, and discuss current and future treatment options. In Part I, the evidence with respect to the spectrum of bacteria present in the CF airway, known as the lung microbiome is discussed. Subsequently, the current approach to treat methicillin-resistant Staphylococcus aureus, gram-negative bacteria, as well as multiple coinfections is reviewed. Newer molecular techniques have demonstrated that the airway microbiome consists of a large number of microbes, and the balance between microbes, rather than the mere presence of a single species, may be relevant for disease pathophysiology. A better understanding of this complex environment could help define optimal treatment regimens that target pathogens without affecting others. Although relevance of these organisms is unclear, the pathologic consequences of methicillin-resistant S. aureus infection in patients with CF have been recently determined. New strategies for eradication and treatment of both acute and chronic infections are discussed. Pseudomonas aeruginosa plays a prominent role in CF lung disease, butmany other nonfermenting gram-negative bacteria are also found in the CF airway. Many new inhaled antibiotics specifically targeting P. aeruginosa have become available with the hope that they will improve the quality of life for patients. Part I concludes with a discussion of how best to treat patients with multiple coinfections.

An official American thoracic society research statement: Comparative effectiveness research in pulmonary, critical care, and sleep medicine

Background: Comparative effectiveness research (CER) is intended to inform decision making in clinical practice, and is central to patientcentered outcomes research (PCOR). Purpose: To summarize key aspects of CER definitions and provide examples highlighting the complementary nature of efficacy and CER studies in pulmonary, critical care, and sleep medicine. Methods: An ad hoc working group of the American Thoracic Society with experience in clinical trials, health services research, quality improvement, and behavioral sciences in pulmonary, critical care, and sleepmedicinewas convened. The group used an iterative consensus process, including a reviewbyAmerican Thoracic Society committees and assemblies. Results: The traditional efficacy paradigm relies on clinical trials with high internal validity to evaluate interventions in narrowly defined populations and in research settings. Efficacy studies address the question, "Can it work in optimal conditions?" The CER paradigm employs a wide range of study designs to understand the effects of interventions in clinical settings. CER studies address the question, "Does it work in practice?" The results of efficacy and CER studies may or may not agree. CER incorporates many attributes of outcomes research and health services research, while placing greater emphasis on meeting the expressed needs of nonresearcher stakeholders (e.g., patients, clinicians, and others). Conclusions: CER complements traditional efficacy research by placing greater emphasis on the effects of interventions in practice, and developing evidence to address the needs of the many stakeholders involved in health care decisions. Stakeholder engagement is an important component of CER. Copyright © 2013 by the American Thoracic Society.

An analysis of implied volatility jump dynamics: Novel functional data representation in crude oil markets

The predominant fear in capital markets is that of a price spike. Commodity markets differ in that there is a fear of both upward and down jumps, this results in implied volatility curves displaying distinct shapes when compared to equity markets. The use of a novel functional data analysis (FDA) approach, provides a framework to produce and interpret functional objects that characterise the underlying dynamics of oil future options. We use the FDA framework to examine implied volatility, jump risk, and pricing dynamics within crude oil markets. Examining a WTI crude oil sample for the 2007–2013 period, which includes the global financial crisis and the Arab Spring, strong evidence is found of converse jump dynamics during periods of demand and supply side weakness. This is used as a basis for an FDA-derived Merton (1976) jump diffusion optimised delta hedging strategy, which exhibits superior portfolio management results over traditional methods.

A-level Mathematics Options – Views of Secondary-level Teachers

The A-level Mathematics qualification is based on a compulsory set of pure maths modules and a selection of applied maths modules with the pure maths representing two thirds of the assessment. The applied maths section includes mechanics, statistics and (sometimes) decision maths. A combination of mechanics and statistics tends to be the most popular choice by far. The current study aims to understand how maths teachers in secondary education make decisions regarding the curriculum options and offers useful insight to those currently designing the new A-level specifications.

Semi-structured interviews were conducted with A-level maths teachers representing 27 grammar schools across Northern Ireland. Teachers were generally in agreement regarding the importance of pure maths and the balance between pure and applied within the A-level maths curriculum. A wide variety of opinions existed concerning the applied options. While many believe that the basic mechanics-statistics (M1-S1) combination is most accessible, it was also noted that the M1-M2 combination fits neatly alongside A-level physics. Lack of resources, timetabling constraints and competition with other subjects in the curriculum hinder uptake of A-level Further Maths.

Teachers are very conscious of the need to obtain high grades to benefit both their pupils and the school’s reputation. The move to a linear assessment system in England while Northern Ireland retains the modular system is likely to cause some schools to review their choice of exam board although there is disagreement as to whether a modular or linear system is more advantageous for pupils. The upcoming change in the specification offers an opportunity to refresh the assessment also and reduce the number of leading questions. However, teachers note that there are serious issues with GCSE maths and these have implications for A-level.

Evaluating environmental enrichment options for commercial broiler chickens

Implications Provision of environmental enrichment in line with that required by welfare-based quality assurance schemesdoes not always appear to lead to clear improvements in broiler chicken welfare. This research perhaps serves to highlightthe deficit in information regarding the ‘real world’ implications of enrichment with perches, string and straw bales.

Introduction Earlier work showed that provision of natural light and straw bales improved leg health in commercial broilerchickens (Bailie et al., 2013). This research aimed to determine if additional welfare benefits were shown in windowedhouses by increasing straw bale provision (Study 1), or by providing perches and string in addition to straw bales (Study 2).

Material and methods Commercial windowed houses in Northern Ireland containing ~23,000 broiler chickens (placed inhouses as hatched) were used in this research which took place in 2011. In Study 1 two houses on a single farm wereassigned to one of two treatments: (1) 30 straw bales per house (1 bale/44m2), or (2) 45 straw bales per house (1bale/29m2). Bales of wheat straw, each measuring 80cm x 40cm x 40cm were provided from day 10 of the rearing cycle,as in Bailie et al. (2013). Treatments were replicated over 6 production cycles (using 276,000 Ross 308 and Cobb birds),and were swapped between houses in each replicate. In Study 2, four houses on a single farm were assigned to 1 of 4treatments in a 2 x 2 factorial design. Treatments involved 2 levels of access to perches (present (24/house), or absent), and2 levels of access to string (present (24/house), or absent), and both types of enrichment were provided from the start of thecycle. Each perch consisted of a horizontal, wooden beam (300 cm x 5 cm x 5cm) with a rounded upper edge resting on 2supports (15 cm high). In the string treatment, 6 pieces of white nylon string (60 cm x 10 mm) were tied at their mid-pointto the wire above each of 4 feeder lines. Thirty straw bales were also provided per house from day 10. This study wasreplicated over 4 production cycles using 368,000 Ross 308 birds. In both studies behaviour was observed between 0900and 1800 hours in weeks 3-5 of the cycle. In Study 1, 8 focal birds were selected in each house each week, and generalactivity, exploratory and social behaviours recorded directly for 10 minutes. In Study 2, 10 minute video recordings weremade of 6 different areas (that did not contain enrichment) of each house each week. The percentage of birds engaged inlocomotion or standing was determined through scan sampling these recordings at 120 second intervals. Four perches andfour pieces of string were filmed for 25 mins in each house that contained these enrichments on one day per week. The totalnumber of times the perch or string was used was recorded, along with the duration of each bout. In both studies, gaitscores (0 (perfect) to 5 (unable to walk)) and latency to lie (measured in seconds from when a bird had been encouraged tostand) were recorded in 25 birds in each house each week. Farm and abattoir records were also used in both studies todetermine the number of birds culled for leg and other problems, mortality levels, slaughter weights, and levels of pododermatitis and hock burn. Data were analysed using SPSS (version 20.0) and treatment and age effects on behaviouralparameters were determined in normally distributed data using ANOVA (‘Straw bale density*week’, or‘string*perches*week’ as appropriate), and in non-normally distributed data using Kuskall-Wallace tests (P<0.05 forsignificance) . Treatment (but not age) effects on performance and health data were determined using the same testsdepending on normality of data.

Results Average slaughter weight, and levels of mortality, culling, hock burn and pododermatitis were not affected bytreatment in either study (P<0.05). In Study 1 straw bale (SB) density had no significant effect on the frequency orduration of behaviours including standing, walking, ground pecking, dust bathing, pecking at bales or aggression, or onaverage gait score (P>0.05). However, the average latency to lie was greater when fewer SB were provided (30SB 23.38s,45SB 18.62s, P<0.01). In Study 2 there was an interaction between perches (Pe) and age in lying behaviour, with higherpercentages of birds observed lying in the Pe treatment during weeks 4 and 5 (week 3 +Pe 77.0 -Pe 80.9, week 4 +Pe 79.5 -Pe 75.2, week 5 +Pe 78.4 -Pe 76.2, P<0.02). There was also a significant interaction between string (S) and age inlocomotory behaviour, with higher percentages of birds observed in locomotion in the string treatment during week 3 butnot weeks 4 and 5 (week 3 +S 4.9 -S 3.9, week 4 +S 3.3 -S 3.7, week 5 +S 2.6 -S 2.8, P<0.04). There was also aninteraction between S and age in average gait scores, with lower gait scores in the string treatment in weeks 3 and 5 (week3: +S 0.7, -S 0.9, week 4: +S 1.5, -S 1.4, week 5: +S 1.9, -S 2.0, P<0.05). On average per 25 min observation there were15.1 (±13.6) bouts of perching and 19.2 (±14.08) bouts of string pecking, lasting 117.4 (±92.7) and 4.2 (±2.0) s for perchesand string, respectively.

Conclusion Increasing straw bale levels from 1 bale/44m2 to 1 bale/29m2 floor space does not appear to lead to significantimprovements in the welfare of broilers in windowed houses. The frequent use of perches and string suggests that thesestimuli have the potential to improve welfare. Provision of string also appeared to positively influence walking ability.However, this effect was numerically small, was only shown in certain weeks and was not reflected in the latency to lie.Further research on optimum design and level of provision of enrichment items for broiler chickens is warranted. Thisshould include measures of overall levels of activity (both in the vicinity of, and away from, enrichment items).