A vertebrate adaptive radiation is assembled from an ancient and disjunct spatiotemporal landscape.

To investigate the origins and stages of vertebrate adaptive radiation, we reconstructed the spatial and temporal histories of adaptive alleles underlying major phenotypic axes of diversification from the genomes of 202 Caribbean pupfishes. On a single Bahamian island, ancient standing variation from disjunct geographic sources was reassembled into new combinations under strong directional selection for adaptation to the novel trophic niches of scale-eating and molluscivory. We found evidence for two longstanding hypotheses of adaptive radiation: hybrid swarm origins and temporal stages of adaptation. Using a combination of population genomics, transcriptomics, and genome-wide association mapping, we demonstrate that this microendemic adaptive radiation of novel trophic specialists on San Salvador Island, Bahamas experienced twice as much adaptive introgression as generalist populations on neighboring islands and that adaptive divergence occurred in stages. First, standing regulatory variation in genes associated with feeding behavior (prlh, cfap20, and rmi1) were swept to fixation by selection, then standing regulatory variation in genes associated with craniofacial and muscular development (itga5, ext1, cyp26b1, and galr2) and finally the only de novo nonsynonymous substitution in an osteogenic transcription factor and oncogene (twist1) swept to fixation most recently. Our results demonstrate how ancient alleles maintained in distinct environmental refugia can be assembled into new adaptive combinations and provide a framework for reconstructing the spatiotemporal landscape of adaptation and speciation.

Severe inbreeding, increased mutation load and gene loss-of-function in the critically endangered Devils Hole pupfish.

Small populations with limited range are often threatened by inbreeding and reduced genetic diversity, which can reduce fitness and exacerbate population decline. One of the most extreme natural examples is the Devils Hole pupfish (Cyprinodon diabolis), an iconic and critically endangered species with the smallest known range of any vertebrate. This species has experienced severe declines in population size over the last 30 years and suffered major bottlenecks in 2007 and 2013, when the population shrunk to 38 and 35 individuals, respectively. Here, we analysed 30 resequenced genomes of desert pupfishes from Death Valley, Ash Meadows and surrounding areas to examine the genomic consequences of small population size. We found extremely high levels of inbreeding (FROH = 0.34-0.81) and an increased amount of potentially deleterious genetic variation in the Devils Hole pupfish as compared to other species, including unique, fixed loss-of-function alleles and deletions in genes associated with sperm motility and hypoxia. Additionally, we successfully resequenced a formalin-fixed museum specimen from 1980 and found that the population was already highly inbred prior to recent known bottlenecks. We thus document severe inbreeding and increased mutation load in the Devils Hole pupfish and identify candidate deleterious variants to inform management of this conservation icon.

Diabolical survival in Death Valley: recent pupfish colonization, gene flow and genetic assimilation in the smallest species range on earth.

One of the most endangered vertebrates, the Devils Hole pupfish Cyprinodon diabolis, survives in a nearly impossible environment: a narrow subterranean fissure in the hottest desert on earth, Death Valley. This species became a conservation icon after a landmark 1976 US Supreme Court case affirming federal groundwater rights to its unique habitat. However, one outstanding question about this species remains unresolved: how long has diabolis persisted in this hellish environment? We used next-generation sequencing of over 13 000 loci to infer the demographic history of pupfishes in Death Valley. Instead of relicts isolated 2-3 Myr ago throughout repeated flooding of the entire region by inland seas as currently believed, we present evidence for frequent gene flow among Death Valley pupfish species and divergence after the most recent flooding 13 kyr ago. We estimate that Devils Hole was colonized by pupfish between 105 and 830 years ago, followed by genetic assimilation of pelvic fin loss and recent gene flow into neighbouring spring systems. Our results provide a new perspective on an iconic endangered species using the latest population genomic methods and support an emerging consensus that timescales for speciation are overestimated in many groups of rapidly evolving species.

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

PURPOSE: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). METHODS: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. RESULTS: In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. CONCLUSION: When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.

Skeletal Health Part 2: Development of a Nurse Practitioner Bone Support Clinic for Urologic Patients.

Part 1 of this article highlighted the potential negative effects of cancer on the skeleton and provided an overview of available treatment options. Part 2 presents a nurse practitioner-led Bone Support Clinic, which was developed for patients with cancer-induced bone disease and cancer therapy-induced bone loss. This clinic, started in 2011 in a university medical center urology/oncology outpatient center in London, England, United Kingdom, has been a collaborative effort among a multidisciplinary team of doctors, nurse practitioners and nurses. Patients have responded positively to the improved continuity of care, and we have been able to assess and treat impending skeletal-related events in a more timely manner The needs of our patient population and problems with the existing service are reviewed, and the importance of a multidisciplinary approach to these problems is discussed. Initiation of a nurse practitioner-led Bone Support Clinic and the impact of timely response to the effects of cancer and cancer therapies on the skeletal system are outlined and offered as a model.

Skeletal Health Part 1: Overview Of Bone Health and Management In the Cancer Setting.

Cancer-induced bone disease and cancer therapy-induced bone loss are significant skeletal problems related to the treatment for urological and other cancers. Our team of specialists and nurse practitioners developed a nurse practitioner-led Bone Support Clinic for urologic cancer patients at a university hospital in London, England, United Kingdom, to address this issue. The clinic has been well-accepted, has made a positive impact on the patient journey, helps to ensure continuity of care, and highlights patients who require assessment or treatment for impending skeletal-related events in a timely fashion. This article has been divided into two parts for improved readability.

Osteonecrosis of the Jaw in Patients Receiving Bone-Targeted Therapies: An Overview--Part I.

Urologic patients receiving bone-targeted therapies are at risk of developing osteonecrosis of the jaw (ONJ). ONJ has historically been associated with bisphosphonate therapy. More recently, RANK-Ligand inhibitors (denosumab) have also been used to reduce the risk of skeletal-related events in patients who have advanced cancers with bone metastases. More than 65% of men with metastatic prostate cancer and nearly 75% of women with metastatic breast cancer are affected by bone metastases. The literature has described ONJ associated with bisphosphonate therapy as bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, with evidence also linking the use of RANK-Ligand inhibitors with osteonecrosis of the jaw, we advocate use of the term "anti-bone resorption therapy-related osteonecrosis of the jaw" (ABRT-ONJ). The term "medication-related osteonecrosis of the jaw" (MRONJ) is now becoming more widespread. There is not a universally accepted definition of ABRT-ONJ, which may have hindered recognition and reporting of the condition. In Part I of this article, a review of current knowledge around the etiology of ABRT-ONJ and incidence data are provided. In Part II, we provide an audit of ONJ in a nurse consultant-led bone support clinic. In the article, we refer to zoledronic acid because this is the bisphosphonate of choice for use in men with prostate cancer in the United Kingdom.

Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

Ciprofloxacin Resistance: A Review of Patients in East London Undergoing Prostate Biopsy.

Transrectal ultrasound guided biopsy of the prostate remains the gold standard investigation to diagnose prostate cancer. Although post-biopsy complications are relatively rare, the risk of sepsis associated with the procedure means that prophylactic antibiotics are paramount. The most widely used antibiotic regimen includes a quinolone, such as ciprofloxacin. Resistance to quinolone antibiotics is rising. In this small pilot study, the incidence of quinolone resistance was 18% in our population of patients attending the prostate biopsy clinic.

Venous thromboembolism (VTE) prophylaxis and urological pelvic cancer surgery: a UK national audit.

OBJECTIVES: To evaluate the use of post-discharge venous thromboembolism (VTE) prophylaxis in UK pelvic cancer centres consistent with national guidelines. METHODS: Data was collected from healthcare professionals from 64 UK pelvic cancer centres. RESULTS: After radical cystectomy (RC), all cancer centres routinely use low-molecular-weight heparin (LMWH) in the perioperative period. After RC 67% of cancer centres use post-discharge LMWH routinely. After radical prostatectomy (RP), 98% of units use perioperative LMWH VTE prophylaxis routinely. After RP, 61% of hospitals always use post-discharge LMWH. In all, 27% of all UK cancer centres reported deaths or serious VTE complications from urological pelvic cancer surgery in the last 2 years. CONCLUSIONS: The National Institute for Health and Care Excellence (NICE) issued explicit guidance of VTE prophylaxis after pelvic and abdominal cancer surgery. Conversion of national guidance into local policy is ≈60% for UK pelvic cancer centres. A lack of good quality evidence is cited as a reason for not adhering to NICE guidance.

Genetic Subdivision and Variation in Selfing Rates Among Central American Populations of the Mangrove Rivulus, Kryptolebias marmoratus.

We used 32 polymorphic microsatellite loci to investigate how a mixed-mating system affects population genetic structure in Central American populations (N = 243 individuals) of the killifish Kryptolebias marmoratus (mangrove rivulus), 1 of 2 of the world's only known self-fertilizing vertebrates. Results were also compared with previous microsatellite surveys of Floridian populations of this species. For several populations in Belize and Honduras, population structure and genetic differentiation were pronounced and higher than in Florida, even though the opposite trend was expected because populations in the latter region were presumably smaller and highly selfing. The deduced frequency of selfing (s) ranged from s = 0.39-0.99 across geographic locales in Central America. This heterogeneity in selfing rates was in stark contrast to Florida, where s > 0.9. The frequency of outcrossing in a population (t = 1 - s) was tenuously correlated with local frequencies of males, suggesting that males are one of many factors influencing outcrossing. Observed distributions of individual heterozygosity showed good agreement with expected distributions under an equilibrium mixed-mating model, indicating that rates of selfing remained relatively constant over many generations. Overall, our results demonstrate the profound consequences of a mixed-mating system for the genetic architecture of a hermaphroditic vertebrate.

Evaluation of physiological response and synchronisation errors during synchronous and pseudosynchronous stimulation trials.

Rhythm perception and synchronisation is musical ability with neural basis defined as the ability to perceive rhythm in music and synchronise body movements with it. The study aimed to check the errors of synchronisation and physiological response as a reaction of the subjects to metrorhythmic stimuli of synchronous and pseudosynchronous stimulation (synchronisation with an externally controlled rhythm, but in reality controlled or produced tone by tapping) Nineteen subjects without diagnosed motor disorders participated in the study. Two tests were performed, where the electromyography signal and reaction time were recorded using the NORAXON system. In addition, physiological signals such as electrodermal activity and blood volume pulse were measured using the Empatica E4. Study 1 consisted of adapting the finger tapping test in pseudosynchrony with a given metrorhythmic stimulus with a selection of preferred, choices of decreasing and increasing tempo. Study 2 consisted of metrorhythmic synchronisation during the heel stomping test. Numerous correlations and statistically significant parameters were found between the response of the subjects with respect to their musical education, musical and sports activities. Most of the differentiating characteristics shown evidence of some group division in the undertaking of musical activities. The use of detailed analyses of synchronisation errors can contribute to the development of methods to improve the rehabilitation process of subjects with motor dysfunction, and this will contribute to the development of an expert system that considers personalised musical preferences.

Schistosomiasis-an endemic parasitic waterborne disease.

Schistosomiasis (or bilharzia) is a chronic waterborne disease caused by parasitic worms or schistosoma in the tropics and sub tropics. Five main species exist, and common to all is its transmission to humans as a result of exposure to infested fresh water, into which the cercariae of the parasite are released by freshwater snails. With the rise of tourism and travel, more people are travelling to countries where schistosomiasis is a risk. Schistosoma haematobium is responsible for urogenital schistosomiasis, in which manifestations range from acute hypersensitivity reactions to bladder disease in the detection of which the nurse cystoscopist can have a significant role. Treatment is highly effective, and the diagnosis should be considered in individuals with possible clinical illness who have travelled to or lived in endemic areas.

Cancer-induced bone disease.

A diagnosis of bone metastases may be devastating for patients with cancer because it suggests that the cancer is incurable and that patients are at increased risk of developing skeletal-related events. The optimal goal for these patients should be to maintain quality of life. Nurses have an important role in the care of patients with cancer-induced bone disease and need to have a good understanding of the effects of bone metastases to ensure prompt management of this condition.

Penile cancer: diagnosis, clinical features and management.

This article aims to provide the reader with an overview of penile cancer. The focus is on clinical and medical aspects to help nurses understand incidence, aetiology, diagnosis and treatment, to enable them educate and support patients affected by this disease. Psychological support of patients and their partners is also emphasised as the effects of penile cancer can be significant.

Out to sea: ocean currents and patterns of asymmetric gene flow in an intertidal fish species.

Passive dispersal via wind or ocean currents can drive asymmetric gene flow, which influences patterns of genetic variation and the capacity of populations to evolve in response to environmental change. The mangrove rivulus fish (Kryptolebias marmoratus), hereafter "rivulus," is an intertidal fish species restricted to the highly fragmented New World mangrove forests of Central America, the Caribbean, the Bahamas, and Florida. Mangrove patches are biological islands with dramatic differences in both abiotic and biotic conditions compared to adjacent habitat. Over 1,000 individual rivulus across 17 populations throughout its range were genotyped at 32 highly polymorphic microsatellites. Range-wide population genetic structure was evaluated with five complementary approaches that found eight distinct population clusters. However, an analysis of molecular variance indicated significant population genetic structure among regions, populations within regions, sampling locations within populations, and individuals within sampling locations, indicating that rivulus has both broad- and fine-scale genetic differentiation. Integrating range-wide genetic data with biophysical modeling based on 10 years of ocean current data showed that ocean currents and the distance between populations over water drive gene flow patterns on broad scales. Directional migration estimates suggested some significant asymmetries in gene flow that also were mediated by ocean currents and distance. Specifically, populations in the center of the range (Florida Keys) were identified as sinks that received migrants (and alleles) from other populations but failed to export individuals. These populations thus harbor genetic variation, perhaps even from extirpated populations across the range, but ocean currents and complex arrangements of landmasses might prevent the distribution of that genetic variation elsewhere. Hence, the inherent asymmetry of ocean currents shown to impact both genetic differentiation and directional migration rates may be responsible for the complex distribution of genetic variation across the range and observed patterns of metapopulation structure.

Psychological impairment in patients urgently referred for prostate and bladder cancer investigations: the role of trait emotional intelligence and perceived social support.

PURPOSE: We aimed to assess the influence of trait emotional intelligence (trait EI) and perceived social support on psychological impairment in a sample of patients urgently referred for prostate and bladder cancer investigations. METHODS: Eighty seven patients (mean age = 62.92; SD = 13.23) were recruited prior to undergoing an investigative procedure for either prostate (n = 45) or bladder (n = 42) cancer. Patients completed measures of psychological impairment (state anxiety and worry) and 82 also competed measures of trait EI and perceived social support. Multivariate linear regression was used to predict the direct and moderated effects of trait EI and perceived social support on psychological impairment. RESULTS: Thirty one percent of patients were considered to be suffering from clinical levels of state anxiety. Trait EI was a significant predictor of state anxiety, worry regarding the appointment, worry regarding the outcome of the appointment and perceived social support. In contrast, perceived social support was not predictive of psychological impairment on any measure and did not moderate the relationship between trait EI and psychological impairment. CONCLUSIONS: Patients urgently referred for urological cancer investigations are a group at risk of psychological impairment and may benefit from healthcare professional support. High trait EI was associated with less state anxiety, less worry and higher perceived social support. There were few consistent effects of perceived social support on psychological impairment. Consideration should be given to the inclusion of trait EI in future models of trauma adaptation.

Prostate cancer overview. Part 1: non-metastatic disease.

Prostate cancer is now recognised as one of the most important medical problems facing the male population, with additional factors such as age, race and familial history amplifying the risk of disease. Part 1 of this two-part article, discusses and provides an overview of the key risk factors, through to diagnosis and management of non-metastatic disease. With the current changing dynamics in healthcare provision both in hospitals and the community setting, the articles aims to inform the wider nursing arena of the key issues that may be raised by men seeking advice and intervention both before and following treatment.