Koenighammond0051

Accurate staging at the time of prostate cancer diagnosis is fundamental to risk stratification and management counseling. Digital rectal exam (DRE) is foundational in clinical staging of prostate cancer, even with a known limited interexaminer agreement and poor sensitivity for detecting extraprostatic disease. We sought to evaluate the prognostic value of DRE for the presence of advanced pathologic features (APFs) following radical prostatectomy (RP).

All patients undergoing RP as primary treatment for clinically localized prostate cancer in the National Cancer Database between 2008 and 2014 were identified. Patients with additional malignancies, prior treatment with radiation or systemic therapy, incongruent clinical staging and DRE findings or without fully evaluable clinical staging were excluded. The primary outcome was the presence of postsurgical APFs, defined as positive surgical margins, nodal disease, or pathologic stage T3 or greater. Multivariable logistic regression analysis was performed to value, particularly for patients with locally advanced disease and potential lymph node disease.

Overall, advanced clinical stage as assessed by DRE was independently associated with an increasing risk of APFs. For individual APFs, the greatest effect is noticed between clinical stage and nodal positivity and less so between clinical stage and positive margins. DRE continues to hold value, particularly for patients with locally advanced disease and potential lymph node disease.Task sharing is a strategy with potential to increase access to effective modern contraceptive methods. This study examines whether community health extension workers (CHEWs) can insert contraceptive implants to the same safety and quality standards as nurse/midwives. We analyze data from 7,691 clients of CHEWs and nurse/midwives who participated in a noninferiority study conducted in Kaduna and Ondo States, Nigeria. Adverse events (AEs) following implant insertions were compared. On the day of insertion AEs were similar among CHEW and nurse/midwife clients-0.5 percent and 0.4 percent, adjusted odds ratio (aOR) 0.92 (95 percent CI 0.38-2.23)-but noninferiority could not be established. At follow-up 6.6 percent of CHEW clients and 2.1 percent of nurse/midwife clients experienced AEs. There was strong evidence of effect modification by State. In the final adjusted model, odds of AEs for CHEW clients in Kaduna was 3.34 (95 percent CI 1.53-7.33) compared to nurse/midwife clients, and 0.72 (95 percent CI 0.19-2.72]) in Ondo. Noninferiority could not be established in either State. Implant expulsions were higher among CHEW clients (142/2987) compared to nurse/midwives (40/3517). Results show the feasibility of training CHEWs to deliver implants in remote rural settings but attention must be given to provider selection, training, supervision, and follow-up to ensure safety and quality of provision.

Attendances to emergency departments (EDs) in the UK are increasing, particularly for younger children. Community services are under increasing pressure and parents may preferentially bring their babies to the ED, even for non-urgent problems. This study aimed to characterise the presenting features, management and disposition of neonatal attendances to a children's ED (CED).

Retrospective observational review of neonatal attendances (≤28days) to the CED at Bristol Royal Hospital for Children (BRHC) from 01/01/2016 to 31/12/2016. Further information was obtained from investigation results and discharge summaries. Data abstracted included sex, age, referral method, presenting complaint, diagnosis, investigations and treatments.

Neonatal attendances increased from 655 to 1,205 from 2008 to 2016. The most common presenting complaints were breathing difficulty (18.1%) and vomiting (8.3%). The most common diagnoses were 'no significant medical problem' (41.9%) and bronchiolitis (10.5%). Half of neonatal attendances to the CED had no investigations performed and most (77.7%) needed advice or observation only.

Many neonates presenting to the CED were well and discharged with observation only. This suggests potential for improving community management and in supporting new parents. Drivers of health policy should consider developing enhanced models of out of hospital care which are acceptable to clinicians and families.

Many neonates presenting to the CED were well and discharged with observation only. This suggests potential for improving community management and in supporting new parents. Drivers of health policy should consider developing enhanced models of out of hospital care which are acceptable to clinicians and families.Increased focus on the development and application of bioavailability-based metal water quality guideline values requires increased understanding of the influence of water chemistry on metal bioavailability and toxicity. Development of empirical models, such as multiple linear regression models, requires the assessment of the influence of individual water quality parameters as toxicity modifying factors. The present study investigated the effect of pH on the lability and toxicity of zinc to a tropical green microalga (Chlorella sp.). Zinc speciation and lability were explored using the Windermere Humic Aqueous Model (WHAM7), ultrafiltration and diffusive gradients in thin-films (DGT). Zinc toxicity increased significantly with increasing pH from pH 6.7 to 8.3, with 50% growth inhibition effect concentrations (EC50) decreasing from 185 to 53 µg.L-1 across the pH range. Linear relationships between DGT-labile zinc and dissolved zinc did not vary across the tested pH range, nor did the linear relationship between dissolved ( less then 0.45 µm) zinc and ultrafiltered ( less then 3 kDa) zinc. Our findings show that zinc toxicity to this freshwater alga is altered as a function of pH across environmentally realistic pH ranges and these toxicity changes could not be explained by zinc speciation and lability as measured by DGT and WHAM7. This article is protected by copyright. All rights reserved.Intraspecific polymorphism in birds, especially plumage colour polymorphism, and the mechanisms that control it are an area of active research in evolutionary biology. The black-headed bulbul (Brachypodius atriceps) is a polymorphic species with two distinct morphs, yellow and grey. This species inhabits the mainland and virtually all continental islands of Southeast Asia where yellow morphs predominate, but on two islands in the Sunda region, Bawean and Maratua, grey morphs are common or exclusive. Here, we generated a high-quality reference genome of a yellow individual and resequenced genomes of multiple individuals of both yellow and grey morphs to study the genetic basis of coloration and population history of the species. Using PCA and STRUCTURE analysis, we found the Maratua Island population (which is exclusively grey) to be distinct from all other B. atriceps populations, having been isolated c. 1.9 million years ago (Ma). BAY613606 In contrast, Bawean grey individuals (a subset of yellow and grey individuals on that island) are embedded within an almost panmictic Sundaic clade of yellow birds. Using FST and dxy to compare variable genomic segments between Maratua and yellow individuals, we located peaks of divergence and identified candidate loci involved in the colour polymorphism. Tests of selection among coding-proteins in high FST regions, however, did not indicate selection on the candidate genes. Overall, we report on some loci that are potentially responsible for the grey/yellow polymorphism in a species that otherwise shows little genetic diversification across most of its range.

Overcoming taxane resistance remains a major clinical challenge in metastatic castrate-resistant prostate cancer (mCRPC). Loss of DNA repair proteins is associated with resistance to anti-microtubule agents. We propose that alterations in DNA damage response (DDR) pathway contribute to taxane resistance, and identification of these alterations may provide a potential therapeutic target to resensitize docetaxel-refractory mCRPC to taxane-based therapy.

Alterations in DDR gene expression in our prostate cancer cell line model of docetaxel-resistance (DU145-DxR) derived from DU-145 cells were determined by DDR pathway-specific polymerase chain reaction array and immunoblotting. The PRKDC gene encoding DNA-PKc (DNA-dependent protein kinase catalytic unit), was noted to be overexpressed and evaluated for its role in docetaxel resistance. Cell viability and clonogenic survival of docetaxel-treated DU145-DxR cells were assessed after pharmacologic inhibition of DNA-PKc with three different inhibitors-NU7441, LTUally, DNA-PKc inhibition did not affect MDR1 activity, indicating that DNA-PKc inhibitors resensitized taxane-resistant cells via an MDR1-independent mechanism.

This study supports a role of DDR genes, particularly, DNA-PKc in promoting resistance to taxanes in mCRPC. Targeting prostatic DNA-PKc may provide a novel strategy to restore taxane sensitivity in taxane-refractory mCRPC.

This study supports a role of DDR genes, particularly, DNA-PKc in promoting resistance to taxanes in mCRPC. Targeting prostatic DNA-PKc may provide a novel strategy to restore taxane sensitivity in taxane-refractory mCRPC.

To further advance the understanding of the species-rich, economically and ecologically important angiosperm order Myrtales in the rosid clade, comprising nine families, approximately 400 genera and almost 14,000 species occurring on all continents (except Antarctica), we tested the Angiosperms353 probe kit.

We combined high-throughput sequencing and target enrichment with the Angiosperms353 probe kit to evaluate a sample of 485 species across 305 genera (76% of all genera in the order).

Results provide the most comprehensive phylogenetic hypothesis for the order to date. Relationships at all ranks, such as the relationship of the early-diverging families, often reflect previous studies, but gene conflict is evident, and relationships previously found to be uncertain often remain so. Technical considerations for processing HTS data are also discussed.

High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.

High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.We studied biotic ligand model (BLM) predictions of toxicity of nickel (Ni) and zinc (Zn) in natural waters from Illinois and Minnesota USA which had combinations of pH, hardness, and dissolved organic carbon (DOC) more extreme than 99.7% of waters in a nationwide database. We conducted 7-d chronic tests with Ceriodaphnia dubia, and 96-hr acute test and 14-d chronic tests with Neocloeon triangulifer, and estimated LC50s and EC20s for both species. Toxicity of Ni and Zn to both species differed among test waters by factors from 8 (Zn tests with C. dubia) to 35 (Zn tests with N. triangulifer). For both species and metals, tests with Minnesota waters (low pH and hardness, high DOC) showed lower toxicity than Illinois waters (high pH, high hardness, low DOC). Recalibration of the Ni BLM to be more responsive to pH-related changes improved predictions of Ni toxicity, especially for C. dubia. We compared several input data scenarios for the Zn BLM, which generally had minor effects on Model Performance Scores (MPS).