Symptom Signatures and Diagnostic Timeliness in Cancer Patients: A Review of Current Evidence.

Early diagnosis is an important aspect of contemporary cancer prevention and control strategies, as the majority of patients are diagnosed following symptomatic presentation. The nature of presenting symptoms can critically influence the length of the diagnostic intervals from symptom onset to presentation (the patient interval), and from first presentation to specialist referral (the primary care interval). Understanding which symptoms are associated with longer diagnostic intervals to help the targeting of early diagnosis initiatives is an area of emerging research. In this Review, we consider the methodological challenges in studying the presenting symptoms and intervals to diagnosis of cancer patients, and summarize current evidence on presenting symptoms associated with a range of common and rarer cancer sites. We propose a taxonomy of cancer sites considering their symptom signature and the predictive value of common presenting symptoms. Finally, we consider evidence on associations between symptomatic presentations and intervals to diagnosis before discussing implications for the design, implementation, and evaluation of public health or health system interventions to achieve the earlier detection of cancer

Evidence for a Black Hole and Accretion Disk in the LINER NGC 4203

We present spectroscopic observations from the Hubble Space Telescope that reveal for the first time the presence of a broad pedestal of Balmer-line emission in the LINER galaxy NGC 4203. The emission-line profile is suggestive of a relativistic accretion disk, and is reminiscent of double-peaked transient Balmer emission observed in a handful of other LINERs. The very broad line emission thus constitutes clear qualitative evidence for a black hole, and spatially resolved narrow-line emission in NGC 4203 can be used to constrain its mass, with M_BH less than 6 x 10^6 solar masses at 99.7% confidence. This value implies a ratio of black-hole mass to bulge mass of less than approximately 7 x 10^-4 in NGC 4203, which is less by a factor of ~3 - 9 than the mean ratio obtained for other galaxies. The availability of an independent constraint on central black-hole mass makes NGC4203 an important testbed for probing the physics of weak active galactic nuclei. Assuming M_BH near the detection limit, the ratio of observed luminosity to the Eddington luminosity is approximately 10^-4. This value is consistent with advection-dominated accretion, and hence with scenarios in which an ion torus irradiates an outer accretion disk that produces the observed double-peaked line emission. Follow-up observations will make it possible to improve the black-hole mass estimate and study variability in the nuclear emission.Comment: 10 pages (LaTeX, AASTeX v4.0), 2 postscript figures, accepted for publication in The Astrophysical Journal Letter

Population variation in early development can determine ecological resilience in response to environmental change

As climate change transforms seasonal patterns of temperature and precipitation, germination success at marginal temperatures will become critical for the long-term persistence of many plant species and communities. If populations vary in their environmental sensitivity to marginal temperatures across a species’ geographical range, populations that respond better to future environmental extremes are likely to be critical for maintaining ecological resilience of the species. / Using seeds from two to six populations for each of nine species of Mediterranean plants, we characterized patterns of among-population variation in environmental sensitivity by quantifying genotype-by-environment interactions (G × E) for germination success at temperature extremes, and under two light regimes representing conditions below and above the soil surface. / For eight of nine species tested at hot and cold marginal temperatures, we observed substantial among-population variation in environmental sensitivity for germination success, and this often depended on the light treatment. Importantly, different populations often performed best at different environmental extremes. / Our results demonstrate that ongoing changes in temperature regime will affect the phenology, fitness, and demography of different populations within the same species differently. We show that quantifying patterns of G × E for multiple populations, and understanding how such patterns arise, can test mechanisms that promote ecological resilience

Double-Peaked Broad Emission Lines in NGC 4450 and Other LINERs

Spectra taken with HST reveal that NGC 4450 emits Balmer emission lines with displaced double peaks and extremely high-velocity wings. This characteristic line profile, previously seen in a few nearby LINERs and in a small fraction of broad-line radio galaxies, can be interpreted as a kinematic signature of a relativistic accretion disk. We can reproduce the observed profile with a model for a disk with a radial range of 1000-2000 gravitational radii and inclined by 27 degrees along the line of sight. The small-aperture HST data also allow us to detect, for the first time, the featureless continuum at optical wavelengths in NGC 4450; the nonstellar nucleus is intrinsically very faint, with M_B = -11.2 mag for D = 16.8 Mpc. We have examined the multiwavelength properties of NGC 4450 collectively with those of other low-luminosity active nuclei which possess double-peaked broad lines and find a number of common features. These objects are all classified spectroscopically as "type 1" LINERs or closely related objects. The nuclear luminosities are low, both in absolute terms and relative to the Eddington rates. All of them have compact radio cores, whose strength relative to the optical nuclear emission places them in the league of radio-loud active nuclei. The broad-band spectral energy distributions of these sources are most notable for their deficit of ultraviolet emission compared to those observed in luminous Seyfert 1 nuclei and quasars. The double-peaked broad-line radio galaxies Arp 102B and Pictor A have very similar attributes. We discuss how these characteristics can be understood in the context of advection-dominated accretion onto massive black holes.Comment: To appear in The Astrophysical Journal. Latex, 15 pages, embedded figures and tabl

Hidden genetic variation in plasticity provides the potential for rapid adaptation to novel environments

Rapid environmental change is forcing populations into novel environments where plasticity will no longer maintain fitness. When populations are exposed to novel environments, evolutionary theory predicts that genetic variation in fitness will increase and should be associated with genetic differences in plasticity. If true, then genetic variation in plasticity can increase adaptive potential in novel environments, and population persistence via rapid adaptation is more likely. To test whether genetic variation in fitness increases in novel environments and is associated with plasticity, we transplanted 8,149 clones of 314 genotypes of a Sicilian daisy (Senecio chrysanthemifolius) within and outside its native range, and quantified genetic variation in fitness, and plasticity in leaf traits and gene expression. Although mean fitness declined by 87% in the novel environment, genetic variance in fitness increased threefold and was correlated with plasticity in leaf traits. High fitness genotypes showed greater plasticity in gene expression, but lower plasticity in most leaf traits. Interestingly, genotypes with greater fitness in the novel environment had the lowest fitness at the native site. These results suggest that standing genetic variation in plasticity could help populations to persist and adapt to novel environments, despite remaining hidden in native environments

Pan-chromatic observations of the remarkable nova LMC 2012

We present the results of an intensive multiwavelength campaign on nova LMC 2012. This nova evolved very rapidly in all observed wavelengths. The time to fall two magnitudes in the V band was only 2 days. In X-rays the super soft phase began 13$\pm$5 days after discovery and ended around day 50 after discovery. During the super soft phase, the \Swift/XRT and \Chandra\ spectra were consistent with the underlying white dwarf being very hot, $\sim$ 1 MK, and luminous, $\sim$ 10$^{38}$ erg s$^{-1}$. The UV, optical, and near-IR photometry showed a periodic variation after the initial and rapid fading had ended. Timing analysis revealed a consistent 19.24$\pm$0.03 hr period in all UV, optical, and near-IR bands with amplitudes of $\sim$ 0.3 magnitudes which we associate with the orbital period of the central binary. No periods were detected in the corresponding X-ray data sets. A moderately high inclination system, $i$ = 60$\pm$10^{\arcdeg}, was inferred from the early optical emission lines. The {\it HST}/STIS UV spectra were highly unusual with only the \ion{N}{5} (1240\AA) line present and superposed on a blue continuum. The lack of emission lines and the observed UV and optical continua from four epochs can be fit with a low mass ejection event, $\sim$ 10$^{-6}$ M$_{\odot}$, from a hot and massive white dwarf near the Chandrasekhar limit. The white dwarf, in turn, significantly illuminated its subgiant companion which provided the bulk of the observed UV/optical continuum emission at the later dates. The inferred extreme white dwarf characteristics and low mass ejection event favor nova LMC 2012 being a recurrent nova of the U Sco subclass.Comment: 18 figures, 6 tables (one online only containing all the photometry

SuperMassive Black Holes in Bulges

We present spatially extended gas kinematics at parsec-scale resolution for the nuclear regions of four nearby disk galaxies, and model them as rotation of a gas disk in the joint potential of the stellar bulge and a putative central black hole. The targets were selected from a larger set of long-slit spectra obtained with the Hubble Space Telescope as part of the Survey of Nearby Nuclei with STIS (SUNNS). They represents the 4 galaxies (of 24) that display symmetric gas velocity curves consistent with a rotating disk. We derive the stellar mass distribution from the STIS acquisition images adopting the stellar mass-to-light ratio normalized so as to match ground-based velocity dispersion measurements over a large aperture. Subsequently, we constrain the mass of a putative black hole by matching the gas rotation curve, following two distinct approaches. In the most general case we explore all the possible disk orientations, alternatively we constrain the gas disk orientation from the dust-lane morphology at similar radii. In the latter case the kinematic data indicate the presence of a central black hole for three of the four objects, with masses of 10^7 - 10^8 solar masses, representing up to 0.025 % of the host bulge mass. For one object (NGC2787) the kinematic data alone provide clear evidence for the presence of a central black hole even without external constraints on the disk orientation. These results illustrate directly the need to determine black-hole masses by differing methods for a large number of objects, demonstrate that the variance in black hole/bulge mass is much larger than previously claimed, and reinforce the recent finding that the black-hole mass is tightly correlated with the bulge stellar velocity dispersion.Comment: 26 pages, 11 Postscript figures, accepted for publication on Ap

Monitoring cryptic amphibians and reptiles in a Florida state park

We monitored cryptic herpetofauna at Savannas Preserve State Park, Florida, by combining artificial cover counts with a quantitative paradigm for constructing and calculating population indices. Weekly indices were calculated from two consecutive days of data collection each week for 7 months from mid-winter to mid-summer in three habitats. Seventeen species were observed at least once, and time trends using index values were followed for six species. Among these, abundance and seasonal pattern information were obtained for an exotic species (greenhouse frog) and a species identified by the Florida Committee on Rare and Endangered Plants and Animals as threatened (Florida scrub lizard). We identified winter as the optimal time in this area to monitor populations for conducting annual assessments. This combined observation and indexing approach could provide managers or researchers with an economical means to quantitatively index population trends for multiple cryptic herpetofauna species simultaneously. Using artificial cover to sample within a population indexing design can be generalized beyond monitoring herpetofauna. Other forms of artificial cover that can be used as observation stations include aquatic artificial substrates, artificial tree cavities, artificial reefs, and other artificial aquatic structures and artificial sea grass units, among many others, and a wide range of taxa are suitable for population monitoring using artificial cover as observation stations in the approach we present, including insects, soil invertebrates, micro and macro aquatic invertebrates, fish, crustaceans, and small mammals

Patient symptom experience prior to a diagnosis of oesophageal or gastric cancer: a multi-methods study.

BACKGROUND: Late stage diagnosis of oesophageal and gastric cancer is common, which limits treatment options and contributes to poor survival. AIM: To explore patients' understanding, experience and presentation of symptoms before a diagnosis of oesophageal or gastric cancer. DESIGN & SETTING: Between May 2016 and October 2017, all patients newly diagnosed with oesophageal or gastric cancer were identified at weekly multidisciplinary team meetings at two large hospitals in England. A total of 321 patients were invited to participate in a survey and secondary care medical record review; 127 (40%) participants responded (102 patients had oesophageal cancer and 25 had gastric cancer). Of these, 26 participated in an additional face-to-face interview. METHOD: Survey and medical record data were analysed descriptively. Interviews were analysed using thematic analysis, informed by the Model of Pathways to Treatment. RESULTS: Participants experienced multiple symptoms before diagnosis. The most common symptom associated with oesophageal cancer was dysphagia (n = 66, 65%); for gastric cancer, fatigue or tiredness (n = 20, 80%) was the most common symptom. Understanding of heartburn, reflux and indigestion, and associated symptoms differed between participants and often contrasted with clinical perspectives. Bodily changes attributed to personal and/or lifestyle factors were self-managed, with presentation to primary care prompted when symptoms persisted, worsened, or impacted daily life, or were notably severe or unusual. Participants rarely presented all symptoms at the initial consultation. CONCLUSION: The patient interval may be lengthened by misinterpretation of key terms, such as heartburn, or misattribution or non-recognition of important bodily changes. Clearly defined symptom awareness messages may encourage earlier help-seeking, while eliciting symptom experience and meanings in primary care consultations could prompt earlier referral and diagnosis.This research was funded by the Medical Research Council and the Raymond and Beverly Sackler Fund as part of EH’s PhD. FMW was supported by an NIHR Clinician Scientist award. JDE was supported by an NHMRC Practitioner Fellowship. JB was supported by the National Institute for Health Research School for Primary Care Research