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Clade-specific (a.k.a. lineage-specific) genes are very common and found at all taxonomic levels and in all clades examined. They can arise by duplication of previously existing genes, which can involve partial truncations or combinations with other protein domains or regulatory sequences. They can also evolve de novo from non-coding sequences, leading to potentially truly novel protein domains. Finally, since clade-specific genes are generally defined by lack of sequence homology with other proteins, they can also arise by sequence evolution that is rapid enough that previous sequence homology can no longer be detected. In such cases, where the rapid evolution is followed by constraint, we consider them to be ontologically non-novel but likely novel at a functional level. In general, clade-specific genes have received less attention from biologists but there are increasing numbers of fascinating examples of their roles in important traits. Here we review some selected recent examples, and argue that attention to clade-specific genes is an important corrective to the focus on the conserved developmental regulatory toolkit that has been the habit of evo-devo as a field. Finally, we discuss questions that arise about the evolution of clade-specific genes, and how these might be addressed by future studies. We highlight the hypothesis that clade-specific genes are more likely to be involved in synapomorphies that arose in the stem group where they appeared, compared to other genes.

Among animals, diploblasts contain two germ layers, endoderm and ectoderm, while triploblasts have a distinct third germ layer called the mesoderm. Spiralians are a group of triploblast animals that have highly conserved development: they share the distinctive spiralian cleavage pattern as well as a unique source of mesoderm, the ectomesoderm. This population of mesoderm is distinct from endomesoderm and is considered a hallmark of spiralian development, but the regulatory network that drives its development is unknown. Here we identified ectomesoderm-specific genes in the mollusc Tritia (aka Ilyanassa) obsoleta through differential gene expression analyses comparing control and ectomesoderm-ablated embryos, followed by in situ hybridization of identified transcripts. We identified a Tritia serpin gene (ToSerpin1) that appears to be specifically expressed in the ectomesoderm of the posterior and head. Ablation of the 3a and 3b cells, which make most of the ectomesoderm, abolishes ToSerpin1 expression, consistent with its expression in these cells. Morpholino knockdown of ToSerpin1 causes ectomesoderm defects, most prominently in the muscle system of the larval head. This is the first gene identified that is specifically implicated in spiralian ectomesoderm development.

We present an analytical solution for the connectivity of a network model with a "non-simultaneous" linking scheme. Despite its simplicity, this model exhibits node-space correlations in the link distribution, and anomalous fluctuations behavior of the time series of the connectivity variable, and a finite-size e ff ect: the maximum number of links occurs away from the critical value of the system parameter. We derive an exact Master Equation for this model using a quantum algebra approach to stochastic processes. Fluctuations are much more important than the mean-field approximation predicts, which we attribute to the heterogeneity in the model. The maximal heterogeneous population corresponds to the critical value of the system. Finally as an explanatory case we evaluate the growth of the network value in relation with the system interconnectedness.

Estimation of the prevalence of undocumented SARS-CoV-2 infections is critical for understanding the overall impact of CoViD-19, and for implementing effective public policy intervention strategies. We discuss a simple yet effective approach to estimate the true number of people infected by SARS-CoV-2, using raw epidemiological data reported by official health institutions in the largest EU countries and the USA.

In some animal groups, the secondary embryonic axis is patterned by a small group of cells, often called an organizer, that signals to other cells to establish the correct pattern of cell fates. The Dpp/BMP2-4 pathway plays a central role in secondary axis patterning in many animals [1-11], but it has not been examined during early axial patterning in spiralian embryogenesis. This is a deeply conserved mode of development found in mollusks, annelids, nemerteans, entoprocts, and some marine platyhelminth groups (reviewed in [12, 13]). In the spiralian embryo of the mollusk Ilyanassa, we find that the Dpp ortholog (IoDpp) is expressed most strongly on the dorsal side, in cells of the embryonic organizer and its neighbors. Phospho-smad staining indicates that the pathway is active in all lineages during organizer signaling, but activation is strongest on the dorsal side. Knockdown of IoDpp by morpholino oligos prevents the development of all structures that require organizer signaling and ventralizes the embryo. Ectopic activation of the pathway can induce eyes and external shell, which require organizer signaling. These results indicate that Dpp/BMP2-4 signaling is a key part of the spiralian organizer and suggest similarity with other metazoan organizers. However, the fact that IoDpp/BMP2-4 is inducing, rather than repressing, the neuroectoderm is a surprising difference that may be conserved among spiralians. These results connect the spiralian organizer to this general aspect of secondary axis patterning but highlight the significant variation across animals in effects of the pathway on particular cell types and tissues.

This paper examines the association between sell-side analysts' short and long-term EPS forecasts, growth rates, and forecast errors, and measures of technological conditions in the firm's industry investment environment. Our contention is analysts' industry knowledge includes an understanding of the technological conditions to which the firms' investments are exposed and how these technological conditions within industries map into future earnings. We predict and find as the horizon lengthens that interactions between technological conditions and current EPS are significantly associated with analysts' EPS and growth forecasts. The long horizon EPS growth results align with Jung, Shane and Yang who suggest analysts' growth forecasts reflect efforts to evaluate the firms' long-run prospects. We also present results for analysts' forecast errors that suggest analysts' technological knowledge is associated with optimistically biased long-term forecasts. Our evidence suggests analysts' industry knowledge includes the implications of technological conditions within industries for firms' future earnings.

Anatomic testing with coronary computed tomography angiography (CCTA) and functional stress testing are both appropriate first-line testing for evaluation of low to intermediate risk chest discomfort in the emergency department (ED). Real world data on rates of revascularization, time to discharge

The SCOT-HEART trial recently showed that the use of coronary computed tomography angiography (CCTA) in stable coronary artery disease (CAD) was associated with lower rates of cardiovascular death or nonfatal myocardial infarction compared to standard care. This was attributed to increased use of

Context. Perinatal palliative care is an area of increasing focus among clinicians supporting newborns and their families. Although not every newborn will survive the neonatal period, assuring their comfort and quality of life remains an imperative for their care providers. It can be challenging to administer medications such as opioids in a minimally invasive yet effective manner. Objectives. To describe the experience using intranasal (IN) fentanyl in the management of distress in a case series of 11 dying neonates. Methods. A retrospective chart review was undertaken of 58 consecutive referrals of newborns and infants aged six months or younger between November 2006 and July 2010 to the Winnipeg Regional Health Authority Pediatric Palliative Care Service to determine how often IN fentanyl was used and review documented responses after the medication. Results. Of 58 referrals, IN fentanyl was used in 11 patients, in all cases for concerns regarding respiratory distress. Chart documentation indicated that fentanyl was tolerated well, with no circumstances of drug-related apnea and no occurrences of chest wall rigidity. In most cases, labored breathing and restlessness settled after medication administration. The average time from administration of the last dose of fentanyl until death was 61 minutes. Conclusion. We found IN fentanyl, which can be administered in a variety of care settings, to be a minimally invasive means of palliating distress in dying newborns and infants. No adverse events related to its use were noted. J Pain Symptom Manage 2012;-:-e-. 2012 U.S. Cancer Pain Relief Committee. Published

Interactions between biochemical functional groups are fundamental to biopolymer self-assembly processes and enzyme-substrate binding and ligand binding, and a key determinant of biopolymer structure and function. To date little quantitative information has been available about their strengths and contributions to stability. Interactions of small solutes have been shown to be composed of additive contributions from interactions of one solute with individual function groups on the other solute (one way interactions). Here we test the hypothesis that solute-solute interactions in water can be dissected using additivity and either an ASA or weighted group-based analysis into contributions from group-group interactions (two way analysis). Data for preferential interactions (μ23 values) of amides with other amides and with aromatics and nucleobases as well as for interactions of alcohols and polyols with aromatics and nucleobases are obtained by osmometry and solubility assays and interpreted to obtain two way potentials (alpha values) for the group group interactions. Some of the most favorable interactions are those that correspond to hydrogen bonding between NH and C=O groups like those in protein 2o structures and in DNA/RNA duplexes. The interaction of aromatic C with amide O is very favorable, providing a second example of a favorable n-π∗ interaction, like that of amide C with amide O (Ref 1).Interactions of amides with Na+ and K+ salts of Hofmeister anions reveal that interactions of these salts with hydrocarbon C and amide N, follow the Hofmeister order (KSCN > KCl > KF; NaClO4 > NaCl > Na2SO4). These data quantify interaction of these salts with the most important protein groups and are useful to interpret or predict Hofmeister effects on protein unfolding m-values.1) Bartlett GJ, Choudhary A, Raines RT, Woolfson DN (2010) Nat Chem Biol 6:615–620.

Spiralian embryogenesis is found in a number of animal phyla, but the molecular mechanisms that pattern these embryos remain poorly understood. A hallmark of spiralian development is the production of tiers of cells, called quartets, that share distinct developmental potentials. Many RNAs have been discovered that are segregated into particular quartets, raising the possibility that such RNAs could be involved in establishing quartet-specific developmental potentials. In the spiralian embryo of the mollusc Ilyanassa, the IoTis11 RNA is segregated into the second and third quartets, then decays in nearly all lineages except for the ventral-anterior cells of the third quartet, 3a and 3b. Previously published fate-mapping studies, extended here, show that 3a and 3b make bilaterally symmetrical contributions to the esophagus, head ectoderm, and larval musculature. Deletion of either 3a or 3b has only mild effects on development, but ablating both cells impairs development of the esophagus and several other organs. Knockdown of IoTis11 with a translation-blocking morpholino oligonucleotide causes a very similar set of phenotypes as ablation of 3a and 3b, showing that translation of this transcript is required for normal development of 3a and 3b. These results show that a segregated RNA is necessary for the cells that inherit it in a spiralian embryo. Given that RNAs are asymmetrically segregated in nearly all the early cleavages in this embryo, these results suggest that the embryo is extensively patterned by segregated factors. Our experiments also uncovered two previously unappreciated non-autonomous events during Ilyanassa development. First, we found that the embryo can regulate to develop normal esophagus after deletion of either 3a or 3b. Second, we found that the 3a or 3b lineages are required for normal development of the digestive glands, which arise from the fourth order macromeres.

This paper argues for a renewed consideration of counterfactuals within geography. Drawing upon Doreen Massey's emphasis on notions of ‘possibility’, ‘chance’, ‘undecidability’ and ‘happenstance’, we argue for an engagement with approaches in the humanities that have addressed such issues directly. We review previous uses of counterfactual method in historical geography, particularly as related to cliometrics and the ‘new economic history’ of the 1960s, but argue that a recent upsurge of interest in other disciplines indicates alternative ways that ‘what-if’ experiments might work in the sub-discipline. Recent counterfactual work outside of geography has had a notably spatial cast, often thinking through the nature of alternative worlds, or using counterfactual strategies that are explicitly concerned with space as well as temporal causality. We set out possible agendas for counterfactual work in historical geography. These include: consideration of the historical geographies within existing counterfactual writings and analyses; suggestions for distinctive ways that historical geographers might think and write counterfactually, including experiments in geographies of happenstance, and the exploration of more-than-human possibilities; analyses of the geography of and in counterfactual writing; and study of the political, ethical and emotional demands that counterfactuals make. This discussion and framework provides an extended introduction to this special feature on counterfactual geographies.

This paper critically examines the role of counterfactual thought and argument in a series of interconnected contexts that span what Paul Gilroy termed the ‘black Atlantic’ and what Ali Mazrui described as ‘Global Africa’. The paper aims to show that a more or less explicit use of conjecture and speculative reasoning has characterised attempts to represent and demand recognition for the horror, inhumanity and injustice of the trans-Atlantic slave trade and New World slavery, and their legacies. To do so, the paper examines a number of interrelated examples, including the campaign for reparations for slavery in the USA; African demands for reparations for slavery, colonialism and neo-colonialism that draw on ideas about the continent's ‘underdevelopment’; and speculative writing that imagines alternate historical geographies of slavery. The paper argues that their concerns with Atlantic slavery and its consequences evince a particular way of engaging with the past that might, at first sight, appear to be aligned with a broader temporal sensibility associated with notions of ghostly return, haunting and trauma. The paper argues, however, that such an assumption is mistaken and that the presence of counterfactualism here illustrates a rather different philosophy of history at work. By highlighting forms of making the past present that are speculative rather than spectral, the paper aims to open up new lines of geographical enquiry that will enhance understanding of Atlantic slavery and its aftermath.

By examining the case of James MacQueen (1778–1870), this paper initiates a research agenda that contributes to what David N. Livingstone has argued remains the most pressing task for historians of geography: to write ‘the historical geography of geography’. Born in Scotland in 1778, MacQueen was one of the many ‘arm-chair’ geographers whose efforts at synthesising contemporary and historical sources were a significant feature of the encounter between Europe and the rest of the world. Indeed, although he never visited Africa, his speculations about the course and termination of the River Niger turned out to be broadly correct. What makes MacQueen a particularly significant figure was the original source of his theory: enslaved Africans in a Caribbean plantation-colony. In this light, a remark that MacQueen's imagination was ‘taken captive by the mystery of the Great River’ carries a dark double-meaning, because ‘captive’ knowledge was the very source of MacQueen's interest in African geography. Beginning with MacQueen's time in Grenada, the paper explores a series of personal relations, textual traces and West African ethno-histories to reveal how his geographical knowledge and expertise were bound up with Atlantic slavery. This shows not only how the colonial economy, centred on the Caribbean, underwrote the production of geographical knowledge about Africa, but also how British geographical discourse and practice might be probed for traces of Atlantic slavery and enslaved African lives. More generally, the case of James MacQueen illuminates a broader field of relationships between Atlantic slavery, West African exploration, and the development of modern British geography in the late eighteenth and first half of the nineteenth centuries. Examining these relationships is key to writing a ‘historical geography of British geography and Atlantic slavery’ and contributes to postcolonial histories of the discipline by revealing the tangled relationships that bound geography and slavery, knowledge and subjugation, that which ‘captivates’ and those held ‘captive’.

Summary During animal development, blast cell lineages are generated by repeated divisions of a mother cell into a series of daughter cells, often with a specific series of distinct fates. Nanos is a translational regulator that is involved in germline development in diverse animals [1–4] and also involved in somatic patterning in insects [5, 6]. Recently, Nanos was found to be required for maintenance of stem cell divisions in the Drosophila germline [7, 8]. We have found that in the mollusk Ilyanassa , Nanos messenger RNA and protein are specifically localized in the mesendodermal blast cell lineage derived from the strongly conserved 4d cell. Nanos activity is required for differentiation of multiple tissues that are derived from the 4d cell, showing that IoNanos is required for somatic development in this embryo. At the cellular level, we show that IoNanos activity is required for the highly stereotyped cleavage pattern of the 4d lineage, the proliferative capacity of the blast cells, and the marked asymmetry of the blast cell divisions. These results suggest that IoNanos is involved in regulating blast cell behaviors in the 4d lineage.

This paper offers a prospectus for a version of historical geography that puts the seas and oceans at the centre of its concerns. This is pursued in three ways. First, via a discussion of the epistemological and historiographic perspectives that might be taken on geographies of the sea, which argues that the view from the ocean can develop geographies of spaces beyond the local and the national, and can attend to the relationships between the human and natural worlds. Second, through a consideration of the imaginative, aesthetic and sensuous geographies of the sea that contends that maritime worlds open up new experiential dimensions and new forms of representation. Finally, in a survey of the material and social worlds of the oceans that suggests that new life can thereby be breathed into current concerns with global political economy, material geographies, the relationship between knowledge and located practice, and the intersections of social and spatial difference. The paper also provides an introduction to a special issue on the historical geography of the sea.

The increasing attention paid by geographers to white identities represents a welcome corrective to research on race and ethnicity that focused on non-white subjectivities and promises to deconstruct the purportedly `normal' or `unremarkable' status often afforded to whiteness. Such work is a vital part of a critical geographical agenda. This paper seeks to contribute to such an agenda by responding to Bonnett [Area 29 (1997) 193, White Identities: Historical and International Perspectives, Prentice Hall, 2000] call for a historical geographical engagement with `white studies'. To do so, it begins by considering how such a critical geography might be spatially and theoretically framed. It then introduces a specific context for such an engagement––the revolt of 1816 by enslaved people of African origin in the British Caribbean colony of Barbados. Reading this not as a single event but as a locus of multiple and conflicting narrations, each linked to particular assertions and contestations of whiteness, the paper argues that geographies of white identities must emphasise struggles between `white' subjects, as well as the role of subaltern acts and representations in white racialisation. This is important if postcolonial, and therefore critical, geographies of white identities are to be produced.

An association has been reported between Wiskott-Aldrich syndrome and necrotizing vasculitis and aneurysmal arterial dilatation. We present here the first endovascular repair of descending thoracic aortic aneurysm in a 35-year-old male patient with the classical Wiskott-Aldrich syndrome phenotype. He had a successful endovascular repair with early discharge from hospital with no postoperative complications. His 1-year follow-up computed tomography scan confirmed appropriate stent position, aneurysm sac resolution with no evidence of endoleak, and no further aneurysm formation.

Spiralian development is shared by several protostome phyla and characterized by regularities in early cleavage, fate map, and larva. Experimental evidence from multiple spiralian species implicates cells in the D quadrant lineage as the organizer of future axial development of the embryo. However, the mechanisms by which the D quadrant is specified differ between species with equal and unequal spiral cleavage. Equally cleaving mollusc embryos establish the D quadrant via cell–cell interactions between the micromeres and macromeres at the 24- to 36-cell stage. In unequally cleaving embryos, the D quadrant is established at the 4-cell stage via asymmetries in the first 2 cell divisions. We have begun to explore the molecular mechanisms of D quadrant patterning in spiralians. Previously, we showed that, in the unequally cleaving embryo of the mollusc Ilyanassa obsoleta, the MAPK pathway is activated and functionally required in 3D and also in the micromeres known to require a signal from 3D. Here, we examine the role of MAPK signaling in 4 spiralians with equal cleavage. In 3 equally cleaving molluscs, the chiton Chaetopleura, the limpet Tectura, and the snail Lymnaea, the MAPK pathway is activated in the 3D cell but not in the overlying micromeres. In the equally cleaving embryo of the polychaete annelid Hydroides, MAPK activation was not detected in the 3D macromere but was observed in one of its daughter cells, 4d. In addition, inhibiting Tectura MAPK activation disrupts differentiation of 3D and cells induced by it, supporting a functional role for MAPK in axis specification in equally cleaving spiralians. Thus, MAPK signaling may have a conserved role in the D quadrant organizer cell 3D in molluscs. However, there have been at least 2 evolutionary changes in the activation of the MAPK pathway during spiralian evolution. MAPK function in the Ilyanassa micromeres is a recent cooption and, since the divergence of annelids and molluscs, there has been a shift in onset of MAPK activation between 3D and 4d. We propose that this latter shift correlates with a change in the timing of specification of the secondary embryonic axis.

Introduction: the diagnosis of thoracic outlet syndrome (TOS) relies heavily on subjective rather than objective assessment criteria. Subsequently, published results after surgical decompression vary considerably. This study aimed to use a symptom-based patient-directed questionnaire to assess the outcome after decompression for TOS. Methods: sixty patients who underwent decompression procedures were identified from a prospectively maintained vascular database. Patient records were analysed for details regarding initial presentation, investigation, type of procedure used for decompression and management. Outcome questionnaires were sent to all identified patients to give a patient-based outcome measure. Results: eighty-four per cent of patients responded. In 90% of these patients there was an improvement in symptoms post-surgery with a median follow up of 43 months. The results were not influenced by the procedure or approach used. Conclusion: surgery remains an effective tool in the management of TOS. A simple patient-directed questionnaire as used in this study could assist in the standardisation of outcome assessment. Eur J Vasc Endovasc Surg 26 , 170-175 (2003)

This paper argues that white Barbadian responses to the renewed anti-slavery campaign from 1823 to 1825 were characterized by a combination of strident assertions of loyalty with a more hostile rhetoric of difference and distance. Drawing on work that emphasizes the place of the anti-slavery campaign in the formulation of English identity, this paper considers where such accounts leave white West Indians, and argues that opposition to anti-slavery was linked to the production of white identity in Barbados. It seeks to explore the complex nature of white resistance to anti-slavery, and thus the ambiguous nature of West Indian whiteness, by focusing on a series of texts produced in the aftermath of ameliorative instructions sent out by the British government and of a major slave revolt in Demerara. In particular, it considers a series of anonymous texts produced during a period of intense anti-Methodist persecution. Locating this anti-Methodism within the broader context of opposition to the anti-slavery campaign, these texts encapsulate the ambivalence of identity and difference, loyalty and hostility that characterizes West Indian whiteness in the early nineteenth century. In this way, the paper aims to contribute to a more nuanced historical geography of white identity.

Purpose: An automated TLD facility has been commissioned and calibrated, and techniques have been developed for the measurement of exit doses in external beam radiotherapy, to enable the routine estimation of delivered tumor doses. Methods and Materials: An automated TLD system, originally intended for use in diagnostic radiology and radiation protection, has been evaluated and configured for the measurement of exit doses in radiotherapy. Linearity, optimum heating cycles and calibration procedures have been determined. At the photon energies used, encapsulated lithium fluoride chips provide insufficient buildup to ensure electronic equilibrium, necessitating calibration to allow for oblique exit surfaces. Expressions are derived to allow the calculation of delivered tumor doses. Results: Under the calibration conditions described, the uncertainty in a single TLD measurement is approximately ±2% (±1 standard deviation ). Over the dose range 0.4-1.5 Gy, TL response is linear. The total heating cycle time, including annealing, is 75 s. Measurements of R exit (the ratio of exit dose with and without full backscatter), used in the estimation of tumor doses, decreases with field size for small fields and varies only slightly for field sizes greater than 7 × 7 cm. Lack of electronic equilibrium leads to a decrease in R exit with increasing exit surface obliquity for all energies considered. Application of the technique to a simulated treatment showed good agreement between estimated and applied tumor doses, when surface obliquity was taken into account. Conclusion: This work describes the commissioning and calibration of an automated TLD facility and demonstrates that exit surface measurements using TLD chips used under conditions where electronic equilibrium was not established, have the potential for identifying discrepancies in delivered tumor doses.

• Administration of intranasal fentanyl to newborns and infants at end-of-life is safe and effective in managing respiratory distress • Intranasal fentanyl is useful in a variety of care settings (hospital and home) for the management of symptoms in newborns and infants at end-of-life • Identified the need to address logistical issues, which include: development of a guideline for the availability of the medication; the use of an atomizer in nasal medication delivery; and supporting staff in this approach to managing symptoms in newborns and infants at end-of-life. Use of Intranasal Fentanyl in Palliative Care of Newborns and Infants

oral diuretics that were successfully treated with subcutaneous furosemide and then transitioned back to oral diuretic therapy. One patient was in the inpatient palliative care unit and another was able to remain in the home and avoided ED return visit and possible rehospitalization entirely. Conclusion. Currently, there is a paucity of literature regarding the efficacy of subcutaneous furosemide despite multiple letters or editorials that mention usage of this route in clinical practice. Benefits of subcutaneous administration include: subcutaneous lines are more easily inserted than IV, are less painful than repeated IM injections, and the subcutaneous linecanremain fora longer duration. As well, subcutaneous lines have a lower risk of infection or other complications than IV access. These two case reports illustrate the utility of subcutaneous furosemide to overcome issues of patient adherence and/or loss of efficacy due to intestinal edema. Routine use of subcutaneous furosemide will require standardized education of home hospice staff to recognize patients that would benefit from such treatment, train patients and family, and to work with pharmacy to ensure availability of requisite supplies and medication.