Invasive ants reduce abundance of small rainforest skinks

Invasive ants are among the world's most damaging invasive species, often directly or indirectly affecting native fauna. Insecticidal baits are the main method for suppressing or eradicating invasive ant populations, but their use must be considered against potential for unintended effects on native organisms. The invasive yellow crazy ant (Anoplolepis gracillipes) is widespread in the tropics, particularly on islands, where they have displaced a range of invertebrates. Effects of this ant on vertebrates, and in continental ecosystems generally, are less studied. We investigated the effects of yellow crazy ants and bait application on rainforest skinks and their invertebrate prey. We compared skink and skink prey abundance across four replicated rainforest site categories: high and low yellow crazy ant sites had both been baited but differed in yellow crazy ant activity; control sites had never had yellow crazy ants or been baited; and buffer sites had never had yellow crazy ants but had been baited. We recorded significantly lower abundance of two small skink species (Lygisaurus laevis and Saproscincus tetradactylus) in high yellow crazy ant sites compared to all other site categories. The differences persisted even after baiting reduced yellow crazy ant activity by 97.8% +/- 0.04% (mean +/- SD). A larger rainforest skink species (Carlia rubrigularis) was not negatively affected by yellow crazy ant invasion. Skink prey abundance was significantly lower in high yellow crazy ant sites compared to control sites and low yellow crazy ant sites, but not compared to buffer sites. These differences did not persist following baiting. We found no evidence that baiting negatively affects skinks or their invertebrate prey. Our data suggest that yellow crazy ants, but not the bait used to treat them, pose a direct threat to small rainforest skinks

Salvage Reirradiation Options for Locally Recurrent Prostate Cancer: A Systematic Review.

Background: Reirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic review describes the oncologic and toxicity outcomes for salvage BT and EBRT [including Stereotactic Body Radiation Therapy (SBRT)]. Methods: An International Prospective Register of Systematic Reviews (PROSPERO) registered (#211875) study was conducted using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. EMBASE and MEDLINE databases were searched from inception to December 2020. For BT, both low dose rate (LDR) and high dose rate (HDR) BT techniques were included. Two authors independently assessed study quality using the 18-item Modified Delphi technique. Results: A total of 39 eligible studies comprising 1967 patients were included (28 BT and 11 SBRT). In 35 studies (90%), the design was single centre and/or retrospective and no randomised prospective studies were found. Twelve BT studies used LDR only, 11 HDR only, 4 LDR or HDR and 1 pulsed-dose rate only. All EBRT studies used SBRT exclusively, four with Cyberknife alone and 7 using both Cyberknife and conventional linear accelerator treatments. Median (range) modified Delphi quality score was 15 (6-18). Median (range) follow-up was 47.5 months (13-108) (BT) and 25.4 months (21-44) (SBRT). For the LDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 71% (48-89.5) and 52.5% (20-79). For the HDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 74% (63-89) and 51% (45-65). For the SBRT studies, the median (range) 2-year bRFS for the SBRT group was 54.9% (40-80). Mean (range) acute and late grade≥3 GU toxicity rates for LDR-BT/HDR-BT/SBRT were 7.4%(0-14)/2%(0-14)/2.7%(0-8.7) and 13.6%(0-30)/7.9%(0-21.3%)/2.7%(0-8%). Mean (range) acute and late grade≥3 GI toxicity rates for LDR-BT/HDR-BT/SBRT were 6.5%(0-19)/0%/0.5%(0-4%) and 6.4%(0-20)/0.1%(0-0.9)/0.2%(0-1.5). One third of studies included Patient Reported Outcome Measures (PROMs). Conclusions: Salvage reirradiation of radiorecurrent prostate cancer using HDR-BT or SBRT provides similar biochemical control and acceptable late toxicity. Salvage LDR-BT is associated with higher late GU/GI toxicity. Challenges exist in comparing BT and SBRT from inconsistencies in reporting with missing data, and prospective randomised trials are needed

Factors affecting outcomes of open surgical repair of pararenal aortic aneurysms: A 10-year experience

PurposeFew large series document surgical outcomes for patients with pararenal abdominal aortic aneurysms (PAAAs), defined as aneurysms including the juxtarenal aorta or renal artery origins that require suprarenal aortic clamping. No standard endovascular alternatives presently exist; however, future endovascular branch graft repairs ultimately must be compared with the gold standard of open repair. To this end, we present a 10-year experience.MethodsBetween 1993 and 2003, 3058 AAAs were repaired. Perioperative variables, morbidity, and mortality were retrospectively assessed. Renal insufficiency was defined as a rise in the concentration of serum creatinine by ≥0.5 mg/dL. Factors predicting complications were identified by multivariate analyses. Morbidity and 30-day mortality were evaluated with multiple logistic regression analysis.ResultsOf a total of 3058 AAA repairs performed, 247 were PAAAs (8%). Mean renal ischemia time was 23 minutes (range, 5 to 60 minutes). Cardiac complications occurred in 32 patients (13%), pulmonary complications in 38 (16%), and renal insufficiency in 54 (22%). Multivariate analysis associated myocardial infarction with advanced age (P = .01) and abnormal preoperative serum creatinine (>1.5 mg/dL) (P = .08). Pulmonary complications were associated with advanced age (P = .03), renal artery bypass (P = .02), increased mesenteric ischemic time (P = .01), suprarenal aneurysm repair (P < .0008), and left renal vein division (P = .01). Renal insufficiency was associated with increased mesenteric ischemic time (P = .001), supravisceral clamping (P = .04), left renal vein division (P = .04), and renal artery bypass (P = .0002), but not renal artery reimplantation or endarterectomy. New dialysis was required in 3.7% (9/242). Abnormal preoperative serum creatinine (>1.5 mg/dL) was predictive of the need for postoperative dialysis (10% vs 2%; P = .04). Patients with normal preoperative renal function had improved recovery (93% vs 36%; P = .0002). The 30-day surgical mortality was 2.5% (6/247) but was not predicted by any factors, and in-hospital mortality was 2.8% (7/247). Median intensive care and hospital stays were 3 and 9 days, respectively, and longer stays were associated with age at surgery (P = .007 and P = .0002, respectively) and any postoperative complication.ConclusionsPAAA repair can be performed with low mortality. Renal insufficiency is the most frequent complication, but avoiding renal artery bypass, prolonged mesenteric ischemia time, or left renal vein transection may improve results

Randomized double-blind trial of pregabalin versus placebo in conjunction with palliative radiotherapy for cancer-induced bone pain

Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown

Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer.

BACKGROUND: Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer. METHOD: Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). RESULTS: A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P \u3c .05), with borderline significances achieved in the other two (P \u3c .1). The signature also predicted biochemical recurrence in patients receiving post-prostatectomy radiotherapy (n = 130, P = .007) or definitive radiotherapy alone (n = 248, P = .035). Lastly, the signature predicted metastasis events in a pooled cohort (n = 631, P = .002). Prognostic significance remained after adjusting for clinic-pathological factors and commercially available prognostic signatures. The signature predicted benefit from hypoxia-modifying therapy in bladder cancer patients (intervention-by-signature interaction test P = .0026), where carbogen and nicotinamide was associated with improved survival only in hypoxic tumours. CONCLUSION: A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients

Triptans attenuate capsaicin-induced CREB phosphorylation within the trigeminal nucleus caudalis: a mechanism to prevent central sensitization?

The c-AMP-responsive element binding protein (CREB) and its phosphorylated product (P-CREB) are nuclear proteins expressed after stimulation of pain-producing areas of the spinal cord. There is evidence indicating that central sensitization within dorsal horn neurons is dependent on P-CREB transcriptional regulation. The objectives of the study were to investigate the expression of P-CREB in cells in rat trigeminal nucleus caudalis after noxious stimulation and to determine whether pre-treatment with specific anti-migraine agents modulate this expression. CREB and P-CREB labelling was investigated within the trigeminal caudalis by immunohistochemistry after capsaicin stimulation. Subsequently, the effect of i.v. pre-treatment with either sumatriptan (n = 5), or naratriptan (n = 7) on P-CREB expression was studied. Five animals pre-treated with i.v. normal saline were served as controls. CREB and P-CREB labelling was robust in all animal groups within Sp5C. Both naratriptan and sumatriptan decreased P-CREB expression (p = 0.0003 and 0.0013) within the Sp5C. Triptans attenuate activation of CREB within the central parts of the trigeminal system, thereby leading to potential inhibition of central sensitization. P-CREB may serve as a new marker for post-synaptic neuronal activation within Sp5C in animal models relevant to migraine

First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer

BACKGROUND AND PURPOSE: Tumour hypoxia is prognostic in head and neck cancer (HNC), associated with poor loco-regional control, poor survival and treatment resistance. The advent of hybrid MRI - radiotherapy linear accelerator or 'MR Linac' systems - could permit imaging for treatment adaptation based on hypoxic status. We sought to develop oxygen-enhanced MRI (OE-MRI) in HNC and translate the technique onto an MR Linac system. MATERIALS AND METHODS: MRI sequences were developed in phantoms and 15 healthy participants. Next, 14 HNC patients (with 21 primary or local nodal tumours) were evaluated. Baseline tissue longitudinal relaxation time (T1) was measured alongside the change in 1/T1 (termed ΔR1) between air and oxygen gas breathing phases. We compared results from 1.5 T diagnostic MR and MR Linac systems. RESULTS: Baseline T1 had excellent repeatability in phantoms, healthy participants and patients on both systems. Cohort nasal concha oxygen-induced ΔR1 significantly increased (p < 0.0001) in healthy participants demonstrating OE-MRI feasibility. ΔR1 repeatability coefficients (RC) were 0.023-0.040 s-1 across both MR systems. The tumour ΔR1 RC was 0.013 s-1 and the within-subject coefficient of variation (wCV) was 25% on the diagnostic MR. Tumour ΔR1 RC was 0.020 s-1 and wCV was 33% on the MR Linac. ΔR1 magnitude and time-course trends were similar on both systems. CONCLUSION: We demonstrate first-in-human translation of volumetric, dynamic OE-MRI onto an MR Linac system, yielding repeatable hypoxia biomarkers. Data were equivalent on the diagnostic MR and MR Linac systems. OE-MRI has potential to guide future clinical trials of biology guided adaptive radiotherapy