We describe a 'super-Earth'-size (2.30 plus or minus 0.16 R sub( oplus)) planet transiting an early K-type dwarf star in the Campaign 4 field observed by the K2 mission. The host star, EPIC ...210363145, was identified as a candidate member of the approximately 120 Myr-old Pleiades cluster based on its kinematics and photometric distance. It is rotationally variable and exhibits near-ultraviolet emission consistent with a Pleiades age, but its rotational period is approximately 20 d and its spectrum contains no H alpha emission nor the Li i absorption expected of Pleiades K dwarfs. Instead, the star is probably an interloper that is unaffiliated with the cluster, but younger (~1.3 Gyr) than the typical field dwarf. We ruled out a false positive transit signal produced by confusion with a background eclipsing binary by adaptive optics imaging and a statistical calculation. Doppler radial velocity measurements limit the companion mass to <2 times that of Jupiter. Screening of the light curves of 1014 potential Pleiades candidate stars uncovered no additional planets. An injection-and-recovery experiment using the K2 Pleiades light curves with simulated planets, assuming a planet population like that in the Kepler prime field, predicts only 0.8-1.8 detections (versus ~20 in an equivalent Kepler sample). The absence of Pleiades planet detections can be attributed to the much shorter monitoring time of K2 (80 d versus 4 yr), increased measurement noise due to spacecraft motion, and the intrinsic noisiness of the stars.
Individual socioeconomic status has been shown to influence the outcomes of patients with chronic obstructive pulmonary disease (COPD). However, contextual factors may also play a role. The objective ...of this study is to evaluate the association between neighborhood socioeconomic disadvantage measured by the area deprivation index (ADI) and COPD-related outcomes.
Residential addresses of SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) subjects with COPD (FEV
/FVC <0.70) at baseline were geocoded and linked to their respective ADI national ranking score at the census block group level. The associations between the ADI and COPD-related outcomes were evaluated by examining the contrast between participants living in the most-disadvantaged (top quintile) to the least-disadvantaged (bottom quintile) neighborhood. Regression models included adjustment for individual-level demographics, socioeconomic variables (personal income, education), exposures (smoking status, packs per year, occupational exposures), clinical characteristics (FEV
% predicted, body mass index) and neighborhood rural status.
A total of 1800 participants were included in the analysis. Participants residing in the most-disadvantaged neighborhoods had 56% higher rate of COPD exacerbation (P<0.001), 98% higher rate of severe COPD exacerbation (P=0.001), a 1.6 point higher CAT score (P<0.001), 3.1 points higher SGRQ (P<0.001), and 24.6 meters less six-minute walk distance (P=0.008) compared with participants who resided in the least disadvantaged neighborhoods.
Participants with COPD who reside in more-disadvantaged neighborhoods had worse COPD outcomes compared to those residing in less-disadvantaged neighborhoods. Neighborhood effects were independent of individual-level socioeconomic factors, suggesting that contextual factors could be used to inform intervention strategies targeting high-risk persons with COPD.
Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in ...providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.
We have developed a novel real‐time quaking‐induced conversion RT‐QuIC‐based assay to detect alpha‐synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and ...Parkinson's disease patients. This assay can detect alpha‐synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT‐QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha‐synucleinopathies.
Priorities for conservation, management, and associated activities will differ based on the interplay between nearness of ecosystems to full recovery from a disturbance (pristineness), susceptibility ...to climate change (environmental susceptibility ES), and capacity of human communities to cope with and adapt to change (social adaptive capacity AC). We studied 24 human communities and adjacent coral reef ecosystems in 5 countries of the southwestern Indian Ocean. We used ecological measures of abundance and diversity of fishes and corals, estimated reef pristineness, and conducted socioeconomic household surveys to determine the AC of communities adjacent to selected coral reefs. We also used Web-based oceanographic and coral mortality data to predict each site's ES to climate warming. Coral reefs of Mauritius and eastern Madagascar had low ES and consequently were not predicted to be affected strongly by warm water, although these sites were differentiated by the AC of the human community. The higher AC in Mauritius may increase the chances for successful self-initiated recovery and protective management of reefs of this island. In contrast, Madagascar may require donor support to build AC as a prerequisite to preservation efforts. The Seychelles and Kenya had high ES, but their levels of AC and disturbance differed. The high AC in the Seychelles could be used to develop alternatives to dependence on coral reef resources and reduce the effects of climate change. Pristineness weighted toward measures of fish recovery was greatest for Kenya's marine protected areas; however, most protected areas in the region were far from pristine. Conservation priorities and actions with realistic chances for success require knowledge of where socioecological systems lie among the 3 axes of environment, ecology, and society.
Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease which impacts the pig industry worldwide. The disease is caused by PRRS viruses (PRRSV-1 and -2) which leads to abortions ...and other forms of reproductive failure in sows and severe respiratory disease in growing pigs. Current PRRSV vaccines provide limited protection; only providing complete protection against closely related strains. The development of improved PRRSV vaccines would benefit from an increased understanding of epitopes relevant to protection, including those recognized by antibodies which possess the ability to neutralize distantly related strains. In this work, a reverse vaccinology approach was taken; starting first with pigs known to have a broadly neutralizing antibody response and then investigating the responsible B cells/antibodies through the isolation of PRRSV neutralizing monoclonal antibodies (mAbs). PBMCs were harvested from pigs sequentially exposed to a modified-live PRRSV-2 vaccine as well as divergent PRRSV-2 field isolates. Memory B cells were immortalized and a total of 5 PRRSV-specific B-cell populations were isolated. All identified PRRSV-specific antibodies were found to be broadly binding to all PRRSV-2 isolates tested, but not PRRSV-1 isolates. Antibodies against GP5 protein, commonly thought to possess a dominant PRRSV neutralizing epitope, were found to be highly abundant, as four out of five B cells populations were GP5 specific. One of the GP5-specific mAbs was shown to be neutralizing but this was only observed against homologous and not heterologous PRRSV strains. Further investigation of these antibodies, and others, may lead to the elucidation of conserved neutralizing epitopes that can be exploited for improved vaccine design and lays the groundwork for the study of broadly neutralizing antibodies against other porcine pathogens.
Farnesyl:protein transferase (FPTase) inhibitors (FTIs) were originally developed as potential anticancer agents targeting the ras oncogene and are currently in clinical trials. Whereas FTIs inhibit ...the farnesylation of Ha-Ras, they do not completely inhibit the prenylation of Ki-Ras, the allele most frequently mutated in human cancers. Whereas farnesylation of Ki-Ras is blocked by FTIs, Ki-Ras remains prenylated in FTI-treated cells because of its modification by the related prenyltransferase, geranylgeranyl:protein transferase type I (GGPTase-I). Hence, cells transformed with Ki-ras tend to be more resistant to FTIs than Ha-ras-transformed cells. To determine whether Ki-ras-transformed cells can be targeted by combining an FTI with a GGPTase-I inhibitor (GGTI), we evaluated potent, selective FTIs, GGTIs, and dual prenylation inhibitors (DPIs) that have both FTI and GGTI activity. We find that in human PSN-1 pancreatic tumor cells, which harbor oncogenic Ki-ras, and in other tumor lines having either wild-type or oncogenic Ki-ras, treatment with an FTI/GGTI combination or with a DPI blocks Ki-Ras prenylation and induces markedly higher levels of apoptosis relative to FTI or GGTI alone. We demonstrate that these compounds can inhibit their enzyme targets in mice by monitoring pancreatic and tumor tissues from treated animals for inhibition of prenylation of Ki-Ras, HDJ2, a substrate specific for FPTase, and Rap1A, a substrate specific for GGPTase-I. Continuous infusion (72 h) of varying doses of GGTI in conjunction with a high, fixed dose of FTI causes a dose-dependent inhibition of Ki-Ras prenylation. However, a 72-h infusion of a GGTI, at a dose sufficient to inhibit Ki-Ras prenylation in the presence of an FTI, causes death within 2 weeks of the infusion when administered either as monotherapy or in combination with an FTI. DPIs are also lethal after a 72-h infusion at doses that inhibit Ki-Ras prenylation. Because 24 h infusion of a high dose of DPI is tolerated and inhibits Ki-Ras prenylation, we compared the antitumor efficacy from a 24-h FTI infusion to that of a DPI in a nude mouse/PSN-1 tumor cell xenograft model and in Ki-ras transgenic mice with mammary tumors. The FTI and DPI were dosed at a level that provided comparable inhibition of FPTase. The FTI and the DPI displayed comparable efficacy, causing a decrease in growth rate of the PSN-1 xenograft tumors and tumor regression in the transgenic model, but neither treatment regimen induced a statistically significant increase in tumor cell apoptosis. Although FTI/GGTI combinations elicit a greater apoptotic response than either agent alone in vitro, the toxicity associated with GGTI treatment in vivo limits the duration of treatment and, thus, may limit the therapeutic benefit that might be gained by inhibiting oncogenic Ki-Ras through dual prenyltransferase inhibitor therapy.
On 5 May 2017, MMS observed a crater‐type flux rope on the dawnside tailward magnetopause with fluctuations. The boundary‐normal analysis shows that the fluctuations can be attributed to nonlinear ...Kelvin‐Helmholtz (KH) waves. Reconnection signatures such as flow reversals and Joule dissipation were identified at the leading and trailing edges of the flux rope. In particular, strong northward electron jets observed at the trailing edge indicated midlatitude reconnection associated with the 3‐D structure of the KH vortex. The scale size of the flux rope, together with reconnection signatures, strongly supports the interpretation that the flux rope was generated locally by KH vortex‐induced reconnection. The center of the flux rope also displayed signatures of guide‐field reconnection (out‐of‐plane electron jets, parallel electron heating, and Joule dissipation). These signatures indicate that an interface between two interlinked flux tubes was undergoing interaction, causing a local magnetic depression, resulting in an M‐shaped crater flux rope, as supported by reconstruction.
Plain Language Summary
Magnetic reconnection and Kelvin‐Helmholtz instability (KHI), two of the most fundamental physical processes occurring within the heliosphere and throughout the Universe, often occur simultaneously on the Earth's magnetopause. Previous studies indicate the importance of nonlinearly developed KH waves, which produce multiple kinetic layers facilitating reconnection both in and out of the velocity shear plane and resulting in the magnetic flux rope. However, these studies significantly lacked detailed in situ observations in quantity as well as appropriate 3‐D analyses of the structure of the KH vortex‐induced flux rope. In this paper, we use detailed observations by the MMS spacecraft to investigate both 2‐D and 3‐D structures of the flux rope developed along the KH waves. We found that two flux tubes interact through reconnection to form a single combined structure, which can explain the occurrence of M‐shaped crater flux rope.
Key Points
MMS observed a magnetic flux rope formed on the boundary of a nonlinear Kelvin‐Helmholtz (KH) wave
Both in‐plane and midlatitude reconnection associated with the 3‐D structure of the KH vortex‐inducedflux rope were identified
A current sheet at the flux rope center supported by reconstruction indicates two flux tubes interlinked to form a crater‐type flux rope
Introduction:
Treatment for differentiated thyroid carcinoma (DTC) in pediatric patients is based mainly on evidence from adult series due to lack of data from pediatric cohorts. Our objective was to ...evaluate presentation, treatment-related complications, and long-term outcome in patients with pediatric DTC in The Netherlands.
Patients and Methods:
In this nationwide study, presentation, complications, and outcome of patients with pediatric DTC (age at diagnosis ≤18 y) treated in The Netherlands between 1970 and 2013 were assessed using medical records.
Results:
We identified 170 patients. Overall survival was 99.4% after a median follow-up of 13.5 years (range 0.3–44.7 y). Extensive follow-up data were available for 105 patients (83.8% women), treated in 39 hospitals. Median age at diagnosis was 15.6 years (range 5.8–18.9 y). At initial diagnosis, 43.8% of the patients had cervical lymph node metastases; 13.3% had distant metastases. All patients underwent total thyroidectomy. Radioiodine was administered to 97.1%, with a median cumulative activity of 5.66 GBq (range 0.74–35.15 GBq). Life-long postoperative complications (permanent hypoparathyroidism and/or recurrent laryngeal nerve injury) were present in 32.4% of the patients. At last known follow-up, 8.6% of the patients had persistent disease and 7.6% experienced a recurrence. TSH suppression was not associated with recurrences (odds ratio 2.00, 95% confidence interval 0.78–5.17, P = .152).
Conclusions:
Survival of pediatric DTC is excellent. Therefore, minimizing treatment-related morbidity takes major priority. Our study shows a frequent occurrence of life-long postoperative complications. Adverse effects may be reduced by the centralization of care, which is crucial for children with DTC.
This Dutch nationwide study on pediatric differentiated thyroid carcinoma reports an excellent survival. However, life-long surgical complications occur frequently.
In this paper, we discuss the outcomes of the follow-up campaign of SN 2018ijp, discovered as part of the Zwicky Transient Facility survey for optical transients. Its first spectrum shows ...similarities to broad-lined Type Ic supernovae around maximum light, whereas later spectra display strong signatures of interaction between rapidly expanding ejecta and a dense H-rich circumstellar medium, coinciding with a second peak in the photometric evolution of the transient. This evolution, along with the results of modeling of the first light-curve peak, suggests a scenario where a stripped star exploded within a dense circumstellar medium. The two main phases in the evolution of the transient could be interpreted as a first phase dominated by radioactive decays, and a later interaction-dominated phase where the ejecta collide with a pre-existing shell. We therefore discuss SN 2018jp within the context of a massive star depleted of its outer layers exploding within a dense H-rich circumstellar medium.
PDF
