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Significance Statement: Acute febrile neutrophilic dermatosis (Sweet syndrome) is a rare idiopathic condition characterized by fever and whole-body rash of tender erythematous plaques of unknown etiology. Otorhinolaryngologic manifestations of the disease can be severe, yet they are sparsely reported in the literature. We present the first documented case of laryngeal involvement of Sweet syndrome. [ABSTRACT FROM AUTHOR]

Chevron's internal Employee Assistance Program and WorkLife Services (EAP/WL) group is comprised of a team of 12 advisors who provide on-site mental health and worklife support for employees, dependents, and retirees across the enterprise. In response to the COVID-19 pandemic, EAP/WL implemented a virtual support group for the first time this year for nursing mothers. The program helps to meet the organizational need within the company, by providing a program that addresses the emotional needs of nursing mothers. The sessions were moderated by an internationally board-certified lactation consultant (IBCLC) with support from two employees: (1) a licensed mental health professional and (2) a worklife advisor. The employees were available to address any emotional and psychologically-related concerns raised by mothers during the monthly discussions. Strategies and best practices for developing a virtual support group for employees are described in this article. Sharing this program may assist other employers in implementing a similar program in support of their employees. [ABSTRACT FROM AUTHOR]

There are many calls to use the COVID 19 crisis as an opportunity for transforming to a future trajectory that is more equitable and environmentally sustainable. What is lacking is a cohesive framework for bringing these calls together. We propose that such transitions could be informed by lessons from three decades of scholarship on abrupt and surprising change in systems of humans and nature. Over time, many social-ecological systems exhibit cycles of change consisting of sequential patterns of growth, development, crisis, and reorganization. A critical phase in the cycle is the brief period after crisis when novelty and innovation can change the future trajectory. Without being prepared for this window of opportunity, deep, systemic change may be unachievable. We propose a three-step process to identify the major drivers of the global system that need to be changed: (1) identifying what society values; (2) identifying the determinants of these valued variables; and (3) identifying the underlying drivers of the determinants and how they need to be changed. A tentative list of five such drivers are identified and discussed: (i) the economic system, (ii) homogenization, (iii) human population growth, size, and densities, (iv) consumption patterns, human ethics, and behavior, and (v) governance. They are linked to seven questions relating to how we might proceed in addressing the drivers. If response to the crisis merely reinforces the existing system, its incompatibility with the natural world and its propensity to increase inequity and conflict will likely increase fragility and lead to another version of the present calamity. If it is a deliberately transformed system that emerges its future will depend on the reorganization process, and the way the system is guided into the future. What is needed is a deliberate, fundamental cultivation of emergence to enable transformation toward better futures in order to avoid an inevitable deepening of a system that ultimately is worse for all. [ABSTRACT FROM AUTHOR]

Approaches to understanding resilience from psychology and sociology emphasize individuals' agency but obscure systemic factors. Approaches to understanding resilience stemming from ecology emphasize system dynamics such as feedbacks but obscure individuals. Approaches from both psychology and ecology examine the actions or attractors available in the present, but neglect how actions taken now can affect the configuration of the social-ecological system in the future. Here, we propose an extension to resilience theory, which we label "pathway diversity", that links existing individual, systems, and temporal theories of resilience into a common framework. In our theory of pathway diversity, resilience is greater if more actions are currently available and can be maintained or enhanced into the future. Using a stylized model of an agricultural social-ecological system, we show how pathway diversity could deliver a context-sensitive method of assessing resilience and guiding planning. Using a stylized state-and-transition model of a poverty trap, we show how pathway diversity is generally consistent with existing definitions of resilience and can illuminate long-standing questions about normative and descriptive resilience. Our results show that pathway diversity advances both theoretical understanding and practical tools for building resilience. [ABSTRACT FROM AUTHOR]

High turnover and short tenures of business school deans disrupt employees, students, performance, and institutional stability. However, we know little about the processes involved in attracting, recruiting, and retaining these influential academic leaders. Previous studies have explored deans ' demographics, their leadership behaviors, and roles as hybrid upper middle managers, but personality traits and job preparation have been largely overlooked. To address the research gap, this quantitative correlational study explored the personality temperament types and years of administrative preparation of 54 deans in accredited US business schools. Our findings showed that 72% of respondents were categorized into two Keirsey temperament groups: GuardiansTM (SJ) and RationalsTM (NT). This research contributes to our understanding of factors impacting the selection and retention of business school deans, with practical implications for hiring, appraisals, leadership and career development. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro , there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function. [ABSTRACT FROM AUTHOR]

The goal of this study was to determine if temporal modulation cutoff frequency was mature in three-month-old infants. Normal-hearing infants and young adults were tested in a single-interval forced-choice observer-based psychoacoustic procedure. Two parameters of the temporal modulation transfer function (TMTF) were estimated to separate temporal resolution from amplitude modulation sensitivity. The modulation detection threshold (MDT) of a broadband noise amplitude modulated at 10 Hz estimated the y-intercept of the TMTF. The cutoff frequency of the TMTF, measured at a modulation depth 4 dB greater than the MDT, provided an estimate of temporal resolution. MDT was obtained in 27 of 33 infants while both MDT and cutoff frequency was obtained in 15 infants and in 16 of 16 adults. Mean MDT was approximately 10 dB poorer in infants compared to adults. In contrast, mean temporal modulation cutoff frequency did not differ significantly between age groups. These results suggest that temporal resolution is mature, on average, by three months of age in normal hearing children despite immature sensitivity to amplitude modulation. The temporal modulation cutoff frequency approach used here may be a feasible way to examine development of temporal resolution in young listeners with markedly immature sensitivity to amplitude modulation. [ABSTRACT FROM AUTHOR]

Electroconductive hydrogels (ECHs) are highly hydrated three-dimensional (3D) networks generated through the incorporation of conductive polymers, nanoparticles, and other conductive materials into polymeric hydrogels. ECHs combine several advantageous properties of inherently conductive materials with the highly tunable physical and biochemical properties of hydrogels. Recently, the development of biocompatible ECHs has been investigated for various biomedical applications, such as tissue engineering, drug delivery, biosensors, flexible electronics, and other implantable medical devices. Several methods for the synthesis of ECHs have been reported, which include the incorporation of electrically conductive materials such as gold and silver nanoparticles, graphene, and carbon nanotubes, as well as various conductive polymers (CPs), such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxyythiophene) into hydrogel networks. These electroconductive composite hydrogels can be used as scaffolds with high swellability, tunable mechanical properties, and the capability to support cell growth both in vitro and in vivo. Furthermore, recent advancements in microfabrication techniques such as 3D bioprinting, micropatterning, and electrospinning have led to the development of ECHs with biomimetic microarchitectures that reproduce the characteristics of the native extracellular matrix (ECM). The combination of sophisticated synthesis chemistries and modern microfabrication techniques have led to engineer smart ECHs with advanced architectures, geometries, and functionalities that are being increasingly used in drug delivery systems, biosensors, tissue engineering, and soft electronics. In this review, we will summarize different strategies to synthesize conductive biomaterials. We will also discuss the advanced microfabrication techniques used to fabricate ECHs with complex 3D architectures, as well as various biomedical applications of microfabricated ECHs. [ABSTRACT FROM AUTHOR]

Abstract Horse meat is a good source of iron with low cholesterol but consumers consider tenderness most important when purchasing meat. Myofibers and intramuscular connective tissue, the main structural components of muscle, play major roles in meat toughness. The effects of myofibers and perimysium characteristics on Warner-Bratzler Shear Force (WBSF) values of horse semimembranosus were investigated on muscles previously assessed as tough (mean WBSF 68.87 ± 3.21 N, n = 8) or tender (mean WBSF 46.21 ± 2.27 N, n = 8). Mean Type IIA myofiber diameter was significantly greater in tender than in tough muscles. Secondary thick perimysium was thicker and collagen fibers more loosely arranged in tender muscles than in tough. A negative correlation was observed between WBSF values and perimysium thickness and a trend between WBSF and intramuscular fat. Adipocytes in perimysium of tender muscles may have contributed to thickening of perimysium and loosened collagen fibers thus contributing to tenderness of the meat. Highlights • Perimysium thickness was negatively correlated with meat toughness. • Myofiber characteristics did not influence horse meat toughness at 3 days post mortem. • Adipocytes may disrupt perimysium collagen fibers and contribute to meat tenderness. [ABSTRACT FROM AUTHOR]

The article presents a brief outline of what resilience, and mentions simplest definition of resilience is the ability to cope with shocks and to keep functioning in much the same kind of way. It mentions two key parts to resilience first, learning how to identify and stay away from tipping points/ thresholds and second, to avoid crossing as yet unknown and unsuspected thresholds, learning about the attributes of a system that confer resilience.

Understanding the profile of oncogene and tumor suppressor gene mutations with their interactions and impact on the prognosis of multiple myeloma (MM) can improve the definition of disease subsets and identify pathways important in disease pathobiology. Using integrated genomics of 1273 newly diagnosed patients with MM, we identified 63 driver genes, some of which are novel, including IDH1, IDH2, HUWE1, KLHL6, and PTPN11. Oncogene mutations are significantly more clonal than tumor suppressor mutations, indicating they may exert a bigger selective pressure. Patients with more driver gene abnormalities are associated with worse outcomes, as are identified mechanisms of genomic instability. Oncogenic dependencies were identified between mutations in driver genes, common regions of copy number change, and primary translocation and hyperdiploidy events. These dependencies included associations with t(4;14) and mutations in FGFR3, DIS3, and PRKD2; t(11;14) with mutations in CCND1 and IRF4; t(14;16) with mutations in MAF, BRAF, DIS3, and ATM; and hyperdiploidy with gain 11q, mutations in FAM46C, and MYC rearrangements. These associations indicate that the genomic landscape of myeloma is predetermined by the primary events upon which further dependencies are built, giving rise to a nonrandom accumulation of genetic hits. Understanding these dependencies may elucidate potential evolutionary patterns and lead to better treatment regimens. [ABSTRACT FROM AUTHOR]

Enterobacteriaceae comprise food spoilage organisms as well as food-borne pathogens including Escherichia coli . Heat resistance in E. coli was attributed to a genomic island called the locus of heat resistance (LHR). This genomic island is also present in several other genera of Enterobacteriaceae , but its function in the enteric pathogens Salmonella enterica and Enterobacter cloacae is unknown. This study aimed to determine the frequency of the LHR in food isolates of E. coli, and its influence on heat resistance in S. enterica and Enterobacter spp. Cell counts of LHR-positive strains of E. coli , S. enterica and E. cloacae were reduced by less than 1, 1, and 4 log (cfu/mL), respectively, after exposure to 60 °C for 5 min, while cell counts of LHR-negative strains of the same species were reduced by more than 7 log (cfu/mL). Introducing an exogenous copy of the LHR into heat-sensitive enteropathogenic E. coli and S. enterica increased heat resistance to a level that was comparable to LHR-positive wild type strains. Cell counts of LHR-positive S. enterica were reduced by less than 1 log(cfu/mL) after heating to 60 °C for 5 min. Survival of LHR-positive strains was improved by increasing the NaCl concentration from 0 to 4%. Cell counts of LHR-positive strains of E. coli and S. enterica were reduced by less than 2 log (cfu/g) in ground beef patties cooked to an internal core temperature of 71 °C. This study indicates that LHR-positive Enterobacteriaceae pose a risk to food safety. [ABSTRACT FROM AUTHOR]

Objective Hypogonadotrophic hypogonadism ( HH) is commonly associated with ageing, obesity and type 2 diabetes. The indications for pituitary imaging are controversial, and current guidelines are based on small case series. Design Retrospective case series from a secondary/tertiary endocrinology referral centre. Patients All men presenting to the Edinburgh Centre for Endocrinology and Diabetes with hypogonadotrophic hypogonadism (testosterone <10 nmol/l and normal prolactin) from 2006 to 2013, in whom pituitary MRI was performed ( n = 281). All HH patients referred in 2011 ( n = 86) were reviewed to assess differences between those selected for pituitary MRI and those who were not scanned. Results Pituitary MRI was normal in 235 men (83·6%), with 24 microadenomas (8·5%), 5 macroadenomas (1·8%) and 1 craniopharyngioma (0·4%) identified. The remaining 16 (5·7%) comprised a range of minor pituitary abnormalities including small cysts and empty sella. All men with abnormal imaging studies had otherwise normal pituitary function. Imaging abnormalities were associated with a significantly lower age at presentation (50 vs 54 years, P = 0·02), but no differences in testosterone or gonadotrophin levels were observed. Current Endocrine Society guidelines would have prompted imaging in only three of six patients with significant pituitary pathology. Conclusions Structural pituitary disease is more common in isolated HH than in the general population, and current guidelines do not accurately identify 'at-risk' individuals. Full anterior pituitary function testing has a low yield in patients presenting with hypogonadism. The optimal strategy for determining the need for pituitary imaging remains uncertain. [ABSTRACT FROM AUTHOR]

Elevated plasma cortisol has been reported following caloric restriction, and may contribute to adverse effects including stress-induced overeating, but results from published studies are inconsistent. To clarify the effects of caloric restriction on plasma cortisol, and to assess cortisol as an indicator of stress during caloric restriction, we conducted a systematic review and meta-analysis of published studies in which cortisol was measured following caloric restriction without other manipulations in humans. We further compared effects of fasting, very low calorie diet (VLCD), and other less intense low calorie diet (LCD), as well as the duration of caloric restriction by meta-regression. Overall, caloric restriction significantly increased serum cortisol level in 13 studies (357 total participants). Fasting showed a very strong effect in increasing serum cortisol, while VLCD and LCD did not show significant increases. The meta-regression analysis showed a negative association between the serum cortisol level and the duration of caloric restriction, indicating serum cortisol is increased in the initial period of caloric restriction but decreased to the baseline level after several weeks. These results suggest that severe caloric restriction causes activation of the hypothalamic-pituitary-adrenal axis, which may be transient, but results in elevated cortisol which could mediate effects of starvation on brain and metabolic function as well as ameliorate weight loss. [ABSTRACT FROM PUBLISHER]

Recent global crises reveal an emerging pattern of causation that could increasingly characterize the birth and progress of future global crises. A conceptual framework identifies this pattern's deep causes, intermediate processes, and ultimate outcomes. The framework shows how multiple stresses can interact within a single social-ecological system to cause a shift in that system's behavior, how simultaneous shifts of this kind in several largely discrete social-ecological systems can interact to cause a far larger intersystemic crisis, and how such a larger crisis can then rapidly propagate across multiple system boundaries to the global scale. Case studies of the 2008-2009 financial-energy and food-energy crises illustrate the framework. Suggestions are offered for future research to explore further the framework's propositions. [ABSTRACT FROM AUTHOR]

Myeloma is characterized by a highly variable clinical outcome. Despite the effectiveness of high-dose therapy, 15% of patients relapse within 1 year. We show that these cases also have a significantly shorter post-relapse survival compared to the others (median 14.9 months vs. 40 months, p = 8.03 × 10− 14). There are no effective approaches to define this potentially distinct biological group such that treatment could be altered. In this work a series of uniformly treated patients with myeloma were used to develop a gene expression profiling (GEP)-based signature to identify this high risk clinical behavior. Gene enrichment analyses applied to the top differentially expressed genes showed a significant enrichment of epigenetic regulators as well as 'stem cell' myeloma genes. A derived 17-gene signature effectively identifies patients at high risk of early relapse as well as impaired overall survival. Integrative genomic analyses showed that epigenetic mechanisms may play an important role on transcription of these genes. [ABSTRACT FROM AUTHOR]

Semiconductor nanocrystals are promising materials for printed optoelectronic devices, but their high surface areas are susceptible to forming defects that hinder charge carrier transport. Furthermore, correlation of chalcogenide nanocrystal (NC) material properties with solar cell operation is not straightforward due to the disorder often induced into NC films during processing. Here, an improvement in long-range ordering of PbSe NCs symmetry that results from halide surface passivation is described, and the effects on chemical, optical, and photovoltaic device properties are investigated. Notably, this passivation method leads to a nanometer-scale rearrangement of PbSe NCs during ligand exchange, improving the long-range ordering of nanocrystal symmetry entirely with inorganic surface chemistry. Solar cells constructed with a variety of architectures show varying improvement and suggest that triplet formation and ionization, rather than carrier transport, is the limiting factor in singlet fission solar cells. Compared to existing protocols, our synthesis leads to PbSe nanocrystals with surface-bound chloride ions, reduced sub-bandgap absorption and robust materials and devices that retain performance characteristics many hours longer than their unpassivated counterparts. [ABSTRACT FROM AUTHOR]

Comparing baseline and stress-induced glucocorticoid hormone levels in animals is a popular tool to assess differences in stress experienced among groups. We compare corticosterone levels in Magellanic Penguins ( Spheniscus magellanicus (J.R. Forster, 1781)) in situations where we hypothesize differences in stress patterns may exist. We compared penguins both within and between breeding seasons, birds breeding at two different locations, penguins at three different ages, penguins that had shown evidence of recent fighting, and, finally, how stress patterns differed for four different penguin species. Throughout a breeding season (settlement, incubation, and chick-rearing), we found no differences in either baseline or stress-induced hormone concentrations. Chick, juvenile, and adult penguins did not differ in baseline corticosterone levels, but juveniles had a reduced stress response. Penguins in one season showed a stress response to capture, likely due to a recent severe weather event. We found no differences in baseline or stress-induced hormone titers for birds from two different breeding locations. Evidence of recent fighting also did not alter baseline corticosterone levels. Finally, among four species of penguins measured (Magellanic, Humboldt ( Spheniscus humboldti Meyen, 1834), Galápagos ( Spheniscus mendiculus Sundevall, 1871), and Rockhopper ( Eudyptes chrysocome (J.R. Forster, 1781)), baseline levels were always consistent, while stress-induced levels were significantly higher in the Rockhopper Penguin only. [ABSTRACT FROM AUTHOR]

OBJECTIVESThe commonest side-effects of GH replacement therapy relate to sodium retention but its mechanism is unclear. In rats, GH inhibits renal and hepatic 11β–hydroxysteroid dehydrogenase (11β–HSD) activities. In man, this action might impair inactivation of cortisol to cortisone in the distal nephron thereby allowing cortisol to activate mineralocorticoid receptors. In this study, we examined the effects of GH replacement on cortisol metabolism. DESIGNA randomized double-blind study comparing 6 months GH replacement with placebo in adults with GH deficiency due to pituitary or hypothalamic disease. PATIENTS6 men and 8 women received placebo and 8 men and 9 women received GH. MEASUREMENTSCortisol and its metabolites were measured in overnight urine samples and in a fasting morning plasma sample at baseline and at 6 months. RESULTSFive patients withdrew from the study, 4 because of adverse effects of GH. Amongst those who completed the study, the effects of GH on cortisol metabolism differed between patients with and without ACTH deficiency. Amongst those receiving hydrocortisone replacement (n = 18), GH had no effect on plasma cortisol/cortisone ratio, or urine tetrahydrocortisols/tetrahydrocortisone ratio, but produced a substantial reduction in total urinary cortisol metabolites (from 1326±191 to 777±229 μg/mmol creatinine; P < 0.01) and an increase in urinary free cortisol/cortisone ratio (from 0.88±0.10 to 2.57±0.74; P < 0.02). By contrast, GH had none of these effects in patients with normal ACTH secretion. There were no changes in blood pressure or plasma electrolytes, aldosterone, or renin activity with GH, and no changes in any variables with placebo. CONCLUSIONSThe increase in cortisol/cortisone ratio in urine but not in plasma, and the lack of effect on hepatic cortisol metabolites, suggests that GH inhibits both the conversion of cortisol to cortisone by renal 11β–HSD2 and the conversion... [ABSTRACT FROM AUTHOR]

ABSTRACT Penguin colonies are highly visited worldwide. Although several studies have addressed how penguins behaviorally respond to tourist visitation at a point in time, nothing is known about their response across the entire breeding season. Furthermore, behavioral responses are driven by complex physiological processes and the basal physiological state of the individual might affect the way it responds to stimuli. To test the hypothesis that annual changes in corticosterone result from animals having different requirements for expressing (or not) the glucocorticoid-mediated behaviors at different times of the year in the context of tourist visitation, we examined circulating and stress-induced corticosterone in Magellanic penguins ( Spheniscus magellanicus) from non-visited areas from the San Lorenzo colony, Peninsula Valdes, Argentina across the breeding season. We also examined the behavioral responses of penguins to a pedestrian approach in tourist-visited and non-visited areas of the colony across the season. Our results showed that circulating levels of corticosterone did not vary across the season; however, stress-induced corticosterone was lowest during molt. Our behavioral results showed that penguins displayed different behavior responses at varying distances depending on the area (visited or non-visited) and stage in the season. Penguins in the tourist area were more tolerant to a human approach than penguins in the non-tourist area. During settlement and molt, penguins showed higher occurrence of behaviors related to self-survival (such as standing, moving farther into the nest, and fleeing), whereas during incubation and chick rearing, penguins displayed mostly a behavior associated with defense and vigilance (such as alternate head turns). Furthermore, penguins allowed a closer approach during incubation, but elicited a subsequent behavior quicker than in the rest of the stages, suggesting that they would be particularly sensitive in this stage. Overall, our results suggest that corticosterone release across the season is more associated with penguins' survival in an extreme environment than with behavioral regulation. From a conservation perspective, we identified that penguins were more sensitive to human approach during incubation, but also molt should be considered as a vulnerable stage because corticosterone secretion is suppressed. © 2014 The Wildlife Society. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a genetic disorder caused by defective steroidogenesis that results in glucocorticoid deficiency; the most common underlying mutation is in the gene that encodes 21-hydroxylase. Life-saving glucocorticoid treatment was introduced in the 1950s, and the number of adult patients is now growing; however, no consensus has been reached on the management of CAH beyond childhood. Adult patients are prescribed a variety of glucocorticoids, including hydrocortisone, prednisone, prednisolone, dexamethasone and combinations of these drugs taken in either a circadian or reverse circadian regimen. Despite these personalized treatments, biochemical control of CAH is only achieved in approximately one-third of patients. Some patients have a poor health status, with an increased incidence of obesity and osteoporosis, and impaired fertility and quality of life. The majority of poor health outcomes seem to relate to inadequate treatment rather than the genotype of the patient. Patients receiving high doses of glucocorticoids and the more potent synthetic long-acting glucocorticoids are at an increased risk of obesity, insulin resistance and a reduced quality of life. Further research is required to optimize the treatment of adult patients with CAH and improve health outcomes. [ABSTRACT FROM AUTHOR]

Singlet exciton fission, the spin-conserving process that produces two triplet excited states from one photoexcited singlet state, is a means to circumvent the Shockley-Queisser limit in single-junction solar cells. Although the process through which singlet fission occurs is not well characterized, some local order is thought to be necessary for intermolecular coupling. Here, we report a triplet yield of 200% and triplet formation rates approaching the diffusion limit in solutions of bis(triisopropylsilylethynyl (TIPS)) pentacene. We observe a transient bound excimer intermediate, formed by the collision of one photoexcited and one ground-state TIPS-pentacene molecule. The intermediate breaks up when the two triplets separate to each TIPS-pentacene molecule. This efficient system is a model for future singlet-fission materials and for disordered device components that produce cascades of excited states from sunlight. [ABSTRACT FROM AUTHOR]

Climate change has recently been implicated in poleward shifts of many tropical species including corals; thus attention focused on higher-latitude coral communities is warranted to investigate possible range expansions and ecosystem shifts due to global warming. As the northern extension of the Florida Reef Tract (FRT), the third-largest barrier reef ecosystem in the world, southeast Florida (25–27° N latitude) is a prime region to study such effects. Most of the shallow-water FRT benthic habitats have been mapped, however minimal data and limited knowledge exist about the coral reef communities of its northernmost reaches off Martin County. First benthic habitat mapping was conducted using newly acquired high resolution LIDAR bathymetry and aerial photography where possible to map the spatial extent of coral reef habitats. Quantitative data were collected to characterize benthic cover and stony coral demographics and a comprehensive accuracy assessment was performed. The data were then analyzed in a habitat biogeography context to determine if a new coral reef ecosystem region designation was warranted. Of the 374 km2 seafloor mapped, 95.2% was Sand, 4.1% was Coral Reef and Colonized Pavement, and 0.7% was Other Delineations. Map accuracy assessment yielded an overall accuracy of 94.9% once adjusted for known map marginal proportions. Cluster analysis of cross-shelf habitat type and widths indicated that the benthic habitats were different than those further south and warranted designation of a new coral reef ecosystem region. Unlike the FRT further south, coral communities were dominated by cold-water tolerant species and LIDAR morphology indicated no evidence of historic reef growth during warmer climates. Present-day hydrographic conditions may be inhibiting poleward expansion of coral communities along Florida. This study provides new information on the benthic community composition of the northern FRT, serving as a baseline for future community shift and range expansion investigations. [ABSTRACT FROM AUTHOR]

The cortisol regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels, particularly in the liver and adipose tissue. The importance of this enzyme in causing metabolic disease was highlighted by transgenic mice which over- or under-expressed 11β-HSD1; consequently, selective 11β-HSD1 inhibitors have been widely developed as novel agents to treat obesity and type 2 diabetes mellitus (T2DM). This review focuses on the importance of 11β-HSD1 in humans which has been more difficult to ascertain. The recent development of a deuterated cortisol tracer has allowed us to quantify in vivo cortisol production by 11β-HSD1. These results have been surprising, as cortisol production rates by 11β-HSD1 are at least equivalent to that of the adrenal glands. The vast majority of this production is by the liver (>90%) with a smaller contribution from subcutaneous adipose tissue and possibly skeletal muscle, but with no detectable production from visceral adipose tissue. This tracer has also allowed us to quantify the tissue-specific regulation of 11β-HSD1 observed in obesity and obesity-associated T2DM, determine the likely basis for this dysregulation, and identify obese patients with T2DM as the group most likely to benefit from selective inhibition of 11β-HSD1. Some of these inhibitors have now reached Phase II clinical development, demonstrating efficacy in the treatment of T2DM. We review these results and discuss whether selective 11β-HSD1 inhibitors are likely to be an important new therapy for metabolic disease. [ABSTRACT FROM AUTHOR]

Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds targeting 11β-HSD1 have been developed. This article reviews the current published literature on compounds that have reached phase II clinical trials in patients with type 2 diabetes, and summarises the preclinical evidence that such agents may be useful for associated conditions, including peripheral vascular disease, coronary artery disease and cognitive decline. In clinical trials, 11β-HSD1 inhibitors have been well tolerated and have improved glycaemic control, lipid profile and blood pressure, and induced modest weight loss. The magnitude of the effects are small relative to other agents, so that further development of 11β-HSD1 inhibitors for the primary therapeutic indication of type 2 diabetes has stalled. Ongoing programmes are focused on additional benefits for cognitive function and other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds targeting 11β-HSD1 have been developed. This article reviews the current published literature on compounds that have reached phase II clinical trials in patients with type 2 diabetes, and summarises the preclinical evidence that such agents may be useful for associated conditions, including peripheral vascular disease, coronary artery disease and cognitive decline. In clinical trials, 11β-HSD1 inhibitors have been well tolerated and have improved glycaemic control, lipid profile and blood pressure, and induced modest weight loss. The magnitude of the effects are small relative to other agents, so that further development of 11β-HSD1 inhibitors for the primary therapeutic indication of type 2 diabetes has stalled. Ongoing programmes are focused on additional benefits for cognitive function and other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Translocations in myeloma are thought to occur solely in mature B cells in the germinal center through class switch recombination (CSR). We used a targeted captured technique followed by massively parallel sequencing to determine the exact breakpoints in both the immunoglobulin heavy chain (IGH) locus and the partner chromosome in 61 presentation multiple myeloma samples. The majority of samples (62%) have a breakpoint within the switch regions upstream of the IGH constant genes and are generated through CSR in a mature B cell. However, the proportion of CSR translocations is not consistent between cytogenetic subgroups. We find that 100% of t(4;14) are CSR-mediated; however, 21% of t(11;14) and 25% of t(14;20) are generated through DH-JH recombination activation genemediated mechanisms, indicating they occur earlier in B-cell development at the pro-B-cell stage in the bone marrow. These 2 groups also generate translocations through receptor revision, as determined by the breakpoints and mutation status of the segments used in 10% and 50% of t(1 1 ;1 4) and t(1 4;20) samples, respectively. The study indicates that in a significant number of cases the translocation- based etiological events underlying myeloma may arise at the pro-B-cell hematological progenitor cell level, much earlier in B-cell development than was previously thought. [ABSTRACT FROM AUTHOR]

Different uses of the terms "drivers," "variables," and "shocks" cause confusion in the literature and in discussions on the dynamics of ecosystems and social--ecological systems. Three main sources of confusion are unclear definition of the system, unclear definition of the role of people, and confusion between variables and drivers. As a contribution to resolving some of the confusion, we offer one interpretation of how the terms might be used. [ABSTRACT FROM AUTHOR]

We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma to define the mutational landscape. Each case was characterized by a median of 24.5 exonic nonsynonymous single-nucleotide variations, and there was a consistently higher number of mutations in the t(4;14) group, but this number did not reach statistical significance. We show that the transition and transversion rates in the 2 subgroups are similar, suggesting that there was no specific mechanism leading to mutation differentiating the 2 groups. Only 3% of mutations were seen in both groups, and recurrently mutated genes include NRAS, KRAS, BRAF, and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct, with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament, and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level In both groups, with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single-cell level using other tumor-acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The Medical Research Council Myeloma IX trial is registered under ISRCTN68454111. (Blood. 2012; 120(5):1077-1086) [ABSTRACT FROM AUTHOR]

Based on the clinical features of myeloma and related malignancies of plasma cells, it has been possible to generate a model system of myeloma progression from a normal plasma cell through smouldering myeloma to myeloma and then plasma cell leukaemia. Using this model system we can study at which points the genetic alterations identified through whole-tumour molecular analyses function in the initiation and progression of myeloma. Further genetic complexity, such as intraclonal heterogeneity, and insights into the molecular evolution and intraclonal dynamics in this model system are crucial to our understandings of tumour progression, treatment resistance and the use of currently available and future treatments. [ABSTRACT FROM AUTHOR]

Increasing ecotourism activity in Argentine Patagonia has led to concerns about the effects of ecotourism on wildlife populations. Penguin breeding colonies are popular tourist destinations. While some species of penguins habituate to human visits, others exhibit negative effects due to disturbance. We studied the effects of tourism on Magellanic Penguins ( Spheniscus magellanicus) at San Lorenzo colony located on the Peninsula Valdes, Chubut, Argentina. We measured behavioural, physiological, and reproductive parameters in birds nesting in tourist-visited and non-visited areas. San Lorenzo has 11 years of visitation history and a low intensity of visitors (~10,000 annually). After 15 min of a simulated tourist visit, penguins in the tourist area showed fewer alternate head turns and lower plasma levels of the stress hormone corticosterone than penguins in a non-visited area. However, penguins showed similar baseline levels of corticosterone between areas as well as similar levels of integrated corticosterone expressed after an acute stressor. Penguin breeding success and chick growth were similar between areas. We compared these findings to results previously published from Punta Tombo, a colony with a longer history (+50 years) and high intensity of annual visitors (>120,000 people). Many (reproductive and behavioural parameters), but not all (physiological parameters), of our findings are similar. That a physiological difference exists may suggest that the previous history of human visitation plays an important role in the response of the birds. Thus, the continuous monitoring of tourist activity is important, as a history of visitation disturbance seems to have an effect on how birds respond to tourists. [ABSTRACT FROM AUTHOR]

Marine organism diversity typically attenuates latitudinally from tropical to colder climate regimes. Since the distribution of many marine species relates to certain habitats and depth regimes, mapping data provide valuable information in the absence of detailed ecological data that can be used to identify and spatially quantify smaller scale (10 s km) coral reef ecosystem regions and potential physical biogeographic barriers. This study focused on the southeast Florida coast due to a recognized, but understudied, tropical to subtropical biogeographic gradient. GIS spatial analyses were conducted on recent, accurate, shallow-water (0-30 m) benthic habitat maps to identify and quantify specific regions along the coast that were statistically distinct in the number and amount of major benthic habitat types. Habitat type and width were measured for 209 evenly-spaced cross-shelf transects. Evaluation of groupings from a cluster analysis at 75% similarity yielded five distinct regions. The number of benthic habitats and their area, width, distance from shore, distance from each other, and LIDAR depths were calculated in GIS and examined to determine regional statistical differences. The number of benthic habitats decreased with increasing latitude from 9 in the south to 4 in the north and many of the habitat metrics statistically differed between regions. Three potential biogeographic barriers were found at the Boca, Hillsboro, and Biscayne boundaries, where specific shallow-water habitats were absent further north; Middle Reef, Inner Reef, and oceanic seagrass beds respectively. The Bahamas Fault Zone boundary was also noted where changes in coastal morphologies occurred that could relate to subtle ecological changes. The analyses defined regions on a smaller scale more appropriate to regional management decisions, hence strengthening marine conservation planning with an objective, scientific foundation for decision making. They provide a framework for similar regional analyses elsewhere. [ABSTRACT FROM AUTHOR]

We present some insights on the use and interpretation of resilience ideas that arose in a conference on "Society's Resilience in Withstanding Disaster." Three points in particular have relevance for those interested in resilience in social-ecological systems: (1) Time as a threshold vs. avoiding quick fixes; (2) Trading risks: specified vs. general resilience; (3) Response origination: building local general resilience, and general resilience in central agencies. In the latter the need is to allow improvisation, and failure, during times of crisis. [ABSTRACT FROM AUTHOR]

In most mammals, the MHC class I molecules are polymorphic and determine the specificity of peptide presentation, whereas the transporter associated with antigen presentation (TAP) heterodimers are functionally monomorphic. In chickens, there are two classical class I genes but only one is expressed at a high level, which can result in strong MHC associations with resistance to particular infectious pathogens. However, the basis for having a single dominantly expressed class I molecule has been unclear. Here we report TAP1 and TAP2 sequences from 16 chicken lines, and show that both genes have high allelic polymorphism and moderate sequence diversity, with variation in positions expected for peptide binding. We analyze peptide translocation in two MHC haplotypes, showing that chicken TAPs specify translocation at three peptide positions, matching the peptide motif of the single dominantly expressed class I molecule. These results show that coevolution between class I and TAP genes can explain the presence of a single dominantly expressed class I molecule in common chicken MHC haplotypes. Moreover, such coevolution in the primordial MHC may have been responsible for the appearance of the antigen presentation pathways at the birth of the adaptive immune system. [ABSTRACT FROM AUTHOR]

Objectives The Tat peptide has been widely used for the intracellular delivery of macromolecules. The aim of this study was to modify the peptide to enable regulation of cellular uptake through a dependency on activation by proteases present in the local environment. Methods The native Tat peptide sequence was altered to inhibit the initial interaction of the peptide with the cell membrane through the addition of the consensus sequence for urokinase plasminogen activator (uPA). uPA expression was characterised and semi-quantitatively rated in three cell lines (U251mg, MDA-MB-231 and HeLa). The modified peptide was incubated with both recombinant enzyme and with cells varying in uPA activity. Cellular uptake of the modified Tat peptide line was compared with that of the native peptide and rated according to uPA activity measured in each cell line. Key findings uPA activity was observed to be high in U251mg and MDA-MB-231 and low in HeLa. In MDA-MB-231 and HeLa, uptake of the modified peptide correlated with the level of uPA expression detected (93 and 52%, respectively). In U251mg, however, the uptake of the modified peptide was much less (19% observed reduction) than the native peptide despite a high level of uPA activity detected. Conclusions Proteolytic activation represents an interesting strategy for the targeted delivery of macromolecules using peptide-based carriers and holds significant potential for further exploitation. [ABSTRACT FROM AUTHOR]

Crash test barriers have been used to assess crashworthiness characteristics of passenger vehicles. Different barriers are employed to examine specific aspects of car structures within certain impact conditions. This paper demonstrates a methodology to create finite element model for Offset Deformable Barrier (ODB) that is used in frontal crash tests. The model is generated using shell elements in LS-DYNA to configure aluminium honeycomb sections. A generic 'Y' cross-section is initially devolved and validated by component test results predict crush behaviour of honeycomb blocks and establish material data before they are used in ODB model. A series of full-scale physical tests has been designed and performed to verify the accuracy of the new FE model for ODB. The model is subjected to four tests with individual boundary conditions and impact speeds while numerical and visual data from CAE are correlated against experiments. The results from FE analysis offer precise correlations with test data and the model has been able to capture detailed deformation patterns for each test setup. [ABSTRACT FROM AUTHOR]

In this article we report on a pilot project investigating the presentation of speech, writing and thought in Early Modern English prose fiction and news writing. The aim of the project is to determine whether discourse presentation changes diachronically and what the function of the various discourse presentation categories were in the Early Modern period. To study this we have built and annotated a small corpus of Early Modern English writing using the model of speech, writing and thought presentation outlined in Semino & Short (2004). We are thus able to compare our findings against those of Semino and Short for Present Day English writing. The quantitative results of our pilot study and our initial qualitative analyses lead to a number of hypotheses which we suggest are suitable for testing on a larger corpus of data. [ABSTRACT FROM AUTHOR]

State-and-transition language for ecosystem dynamics was articulated in a 1989 paper written by Imanuel Noy-Meir in collaboration with Westoby and Walker. That paper has been surprisingly influential considering that the publication it appeared in, Journal of Range Management, serves a relatively small community of researchers. Here we trace the wider history within which the paper sits, both the context that led up to its being written and its influence subsequently. Our aim is to explain Noy-Meir's distinctive and constructive role, at several points in the history. [ABSTRACT FROM AUTHOR]

Abstract: A series of substrate-based α-keto-β-aldehyde (glyoxal) sequences have been synthesised and evaluated as inhibitors of the caspase family of cysteine proteases. A number of potent inhibitor sequences have been identified. For example, a palmitic acid containing sequence pal-Tyr-Val-Ala-Asp-glyoxal was demonstrated to be an extremely effective inhibitor of caspase-1, inhibiting not only the action of the protease against synthetic fluorogenic substrates (K i =0.3nM) but also blocking its processing of pro-interleukin-1beta (pro-IL-1β). In addition, the peptide Ac-Asp-Glu-Val-Asp-glyoxal, which is based on the consensus cleavage sequence for caspase-3, is a potent inhibitor of this protease (K i =0.26nM) yet only functions as a comparatively modest inhibitor of caspase-1 (K i =451nM). Potent inhibitor sequences were also identified for caspases-6 and -8. However, the degree of discrimination between the family members is limited. The ability of Ac-Asp-Glu-Val-Asp-glyoxal to block caspase-3 like activity in whole cells and to delay the development of apoptosis was assessed. When tested against caspase-3 like activity in cell lysates, Ac-Asp-Glu-Val-Asp-glyoxal displayed effective inhibition similar to that observed against recombinant caspase-3. Treatment of whole cells with this potent caspase-3 inhibitor was however, not sufficient to significantly stall the development of apoptosis in-vitro. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study which found that expression levels of the mammalian target of rapamycin inhibitor DEPTOR can be associated to improved survival in patients treated with thalidomide.

Productivity enhancement has traditionally been the main focus of agricultural research to alleviate poverty and enhance food security of poor farmers in the developing world. Recently, the harmful impact of climate change, economic volatility, and other external shocks on poor farmers has led to concern that resilience should feature alongside productivity as a major objective of research. The applicability of recent work on resilient social-ecological systems to the problems of poor farmers is reviewed, and proposals are made for issues that need to be addressed in determining when and how enhanced resilience might become an objective of research. [ABSTRACT FROM AUTHOR]

Reef fish assemblage relationships with in situ and lidar topographic measurements across the seascape were analyzed to evaluate the possibility of using lidar metrics as a proxy for prediction models. In situ topographic complexity (i.e., linear rugosity) was measured from 346 point-count fish surveys spanning the reef seascape. Lidar topographic measurements (i.e., surface rugosity, elevation, and volume) were obtained from a high-resolution lidar bathymetric dataset of each survey's footprint. The survey sites were characterized by an independently derived benthic habitat map. Reef fish abundance and species richness appeared to increase with increasing topographic complexity. Although significant, the relationship was weak. Habitat characterization showed that these relationships changed across the seascape. The relationship between topographic complexity and species richness was more pronounced in shallow habitats, whereas, topographic complexity related more closely to abundance in offshore habitats. In situ rugosity measurement yielded the best explanation of fish assemblage structure parameters, but the weaker lidar metric correlations followed similar trends. Accordingly, lidar-measured topographic complexity may be a useful metric for reef fish distributional models. Such predictive models could have many scientific and management applications including: estimating fish stocks, viewing data trends across the seascape, and designing marine protected areas. However, better understanding of the appropriate spatial scale, measurement scale, and fish operational scale is needed, as well as more research on the dynamics of how reef fishes relate to topographic complexity and other ecological factors influencing distributions across the seascape. [ABSTRACT FROM AUTHOR]

Producing thematic coral reef benthic habitat maps from single-beam acoustic backscatter has been hindered by uncertainties in interpreting the acoustic energy parameters E1 (tail of 1st echo) and E2 (complete 2nd echo), typically limiting such maps to sediment classification schemes. In this study, acoustic interpretation was guided by high-resolution lidar (LIght Detection And Ranging) bathymetry. Each acoustic record, acquired from a BioSonics DT-X echosounder and multiplexed 38 and 418 kHz transducers, was paired with a spatially-coincident value of a lidar-derived proxy for topographic complexity, reef-volume (RV), and its membership to one of eight benthic habitat classes, delineated from lidar imagery, ground-truthing, and characterization of epibenthic biota. The discriminatory capabilities of the 38 and 418 kHz signals were generally similar. Individually, the E1 and E2 of both frequencies differentiated between levels of RV and most habitat classes, but could not unambiguously delineate habitats. Plotted in E1:E2 Cartesian space, both frequencies formed two main groupings: uncolonized sand habitats and colonized reefal habitats. E1 and E2 were significantly correlated at both frequencies: positively over sand habitats and negatively over reefal habitats, where the scattering influence of epibenthic biota strengthened the E1:E2 interdependence. However, sufficient independence existed between E1 and E2 to clearly delineate habitats using the multi-echo E1:E2 bottom ratio method. The point-by-point calibration provided by the lidar data was essential for resolving the uncertainties surrounding the factors informing the acoustic parameters in a large, survey-scale dataset. The findings of this study indicate that properly interpreted single-beam acoustic data can be used to thematically categorize coral reef benthic habitats. [ABSTRACT FROM AUTHOR]

We present a resilience-based approach for assessing sustainability in a sub-catchment of the Murray-Darling Basin in southeast Australia. We define the regional system and identify the main issues, drivers, and potential shocks, then assess both specified and general resilience. The current state of the system is a consequence of changes in resource use. We identify ten known or possible biophysical, economic, and social thresholds operating at different scales, with possible knock-on effects between them. Crossing those thresholds may result in irreversible changes in goods and services generated by the region. Changes in resilience, in general, reflect a pattern of past losses with some signs of recent improvements. Interventions in the system for managing resilience are constrained by current governance, and attention needs to be paid to the roles and capacities of the various institutions. An overview of the current state of the system and likely future trends suggests that transformational change in the region be seriously considered. [ABSTRACT FROM AUTHOR]

The article discusses a study on the levels of genetic structuring among Spheniscus magellanicus, also known as Magellanic Penguin, colonies that were distributed throughout several reproductive regions of the South Atlantic Ocean. In order to estimate such levels, mitochondrial DNA sequences and microsatellite markers were used. Results of the microsatellite analysis showed levels of genetic variability based on allelic and heterozygosity diversity.