Flyway-scale GPS tracking reveals migratory routes and key stopover and non-breeding locations of lesser yellowlegs.

Many populations of long-distance migrant shorebirds are declining rapidly. Since the 1970s, the lesser yellowlegs (Tringa flavipes) has experienced a pronounced reduction in abundance of ~63%. The potential causes of the species' decline are complex and interrelated. Understanding the timing of migration, seasonal routes, and important stopover and non-breeding locations used by this species will aid in directing conservation planning to address potential threats. During 2018-2022, we tracked 118 adult lesser yellowlegs using GPS satellite tags deployed on birds from five breeding and two migratory stopover locations spanning the boreal forest of North America from Alaska to Eastern Canada. Our objectives were to identify migratory routes, quantify migratory connectivity, and describe key stopover and non-breeding locations. We also evaluated predictors of southbound migratory departure date and migration distance. Individuals tagged in Alaska and Central Canada followed similar southbound migratory routes, stopping to refuel in the Prairie Pothole Region of North America, whereas birds tagged in Eastern Canada completed multi-day transoceanic flights covering distances of >4000 km across the Atlantic between North and South America. Upon reaching their non-breeding locations, lesser yellowlegs populations overlapped, resulting in weak migratory connectivity. Sex and population origin were significantly associated with the timing of migratory departure from breeding locations, and body mass at the time of GPS-tag deployment was the best predictor of southbound migratory distance. Our findings suggest that lesser yellowlegs travel long distances and traverse numerous political boundaries each year, and breeding location likely has the greatest influence on migratory routes and therefore the threats birds experience during migration. Further, the species' dependence on wetlands in agricultural landscapes during migration and the non-breeding period may make them vulnerable to threats related to agricultural practices, such as pesticide exposure.

Implementing intensity modulated radiotherapy to the prostate bed: dosimetric study and early clinical results.

Salvage intensity modulated radiotherapy (IMRT) to the prostate bed has hardly been studied so far. We present here a feasibility study and early clinical results for 10 patients. These patients were selected on the basis of having either a biochemical relapse or high risk histology after prostatectomy. They were treated using "sliding-window" IMRT to 68 Gy in 34 fractions. Three-dimensional conformal radiotherapy (3D-CRT) plans were generated using the same planning computed tomography data set. Dose coverage of planning target volumes (PTVs) and of organs-at-risk (OAR, namely: rectum, bladder, and femoral heads) were compared. Acute toxicity and chronic toxicity were measured using the Common Toxicity Criteria for Adverse Events version 3.0 scale. IMRT significantly reduces the dose above the prescription dose given to the PTV1 (mean dose: IMRT 67.2 Gy vs 3D-CRT 67.7 Gy (p = 0.0137)), without altering dose coverage for PTV2 (mean dose: IMRT 68.1 Gy vs 3D-CRT 68.0 Gy (p = 0.3750)). Doses to OAR were lower with IMRT and differences were statistically significant (mean dose: IMRT 51.4 Gy vs 3D-CRT 56.6 Gy for rectum (p = 0.002), IMRT 45.1 Gy vs 3D-CRT 53.1 Gy for bladder (p = 0.002), and IMRT 26.1 Gy vs 3D-CRT 28.4 Gy for femoral heads (p = 0.0059)). There was no acute or chronic genitourinary or gastrointestinal toxicity >1 with a median follow-up of 38 months. IMRT to the prostatic fossa is feasible and reduces dose to OAR, with consequential limited toxicity.

Three Years of Salvage IMRT for Prostate Cancer: Results of the Montpellier Cancer Center.

Background. To assess the feasibility of salvage intensity-modulated radiation Therapy (IMRT) and to examine clinical outcome. Patients and Methods. 57 patients were treated with salvage IMRT to the prostate bed in our center from January, 2007, to February, 2010. The mean prescription dose was 68 Gy in 34 fractions. Forty-four patients received concomitant androgen deprivation. Results. Doses to organs at risk were low without altering target volume coverage. Salvage IMRT was feasible without any grade 3 or 4 acute gastrointestinal or urinary toxicity. With a median follow-up of 21 months, one grade 2 urinary and 1 grade ≥2 rectal late toxicities were reported. Biological relapse-free survival was 96.5% (2.3% (1/44) relapsed with androgen suppression and 7.7% (1/13) without). Conclusion. Salvage IMRT is feasible and results in low acute and chronic side-effects. Longer follow-up is warranted to draw conclusions in terms of oncologic control.

Eight years of IMRT quality assurance with ionization chambers and film dosimetry: experience of the Montpellier Comprehensive Cancer Center.

BACKGROUND: To present the results of quality assurance (QA) in IMRT of film dosimetry and ionization chambers measurements with an eight year follow-up. METHODS: All treatment plans were validated under the linear accelerator by absolute and relative measures obtained with ionization chambers (IC) and with XomatV and EDR2 films (Kodak). RESULTS: The average difference between IC measured and computed dose at isocenter with the gantry angle of 0° was 0.07 ± 1.22% (average ± 1 SD) for 2316 prostate, 1.33 ± 3.22% for 808 head and neck (h&n), and 0.37 ± 0.62% for 108 measurements of prostate bed fields. Pelvic treatment showed differences of 0.49 ± 1.86% in 26 fields for prostate cases and 2.07 ± 2.83% in 109 fields of anal canal.Composite measurement at isocenter for each patient showed an average difference with computed dose of 0.05 ± 0.87% for 386 prostate, 1.49 ± 1.86% for 158 h&n, 0.37 ± 0.34% for 23 prostate bed, 0.80 ± 0.28% for 4 pelvis, and 2.31 ± 0.56% for 17 anal canal cases. On the first 250 h&n analyzed by film in absolute dose, the average of the points crossing a gamma index 3% and 3 mm was 93%. This value reached 99% for the prostate fields. CONCLUSION: More than 3500 beams were found to be within the limits defined as validated for treatment between 2001 and 2008.

TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation.

Galpha(i)-coupled receptors comprise a diverse family of receptors that induce transformation by largely unknown mechanisms. We previously found that the Galpha(i)-coupled dopamine-D2short (D2S) receptor transforms Balb-D2S cells via Gαi3. To identify new Gαi effectors, a yeast two-hybrid screen was done using constitutively active Gαi3-Q204L as bait, and tumor necrosis factor-alpha (TNFα)-induced protein 8 (TNFAIP8, SCC-S2/NDED/GG2-1) was identified. In contrast, TNFAIP8-related TIPE1 and TIPE2 showed a very weak interaction with Gαi3. In yeast mating, in vitro pull-down, co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) assays, TNFAIP8 preferentially interacted with activated Gαi proteins, consistent with direct Gαi-TNFAIP8 coupling. Over-expression or depletion of TNFAIP8 using antisense constructs in Balb-D2S cells did not affect D2S-induced signaling to Gαi-dependent inhibition of cAMP. In contrast, antisense depletion of TNFAIP8 completely inhibited spontaneous and D2S-induced foci formation, consistent with a role for TNFAIP8 in Gαi-dependent transformation. To address possible mechanisms, the effect of D2S signaling via TNFAIP8 on TNFα action was examined. D2S receptor activation inhibited TNFα-induced cell death in Balb-D2S cells, but not in cells depleted of TNFAIP8. However, depletion of TNFAIP8 did not prevent D2S-induced inhibition of TNFα-mediated caspase activation, suggesting that D2S/TNFAIP8-induced protection from TNFα-induced cell death is caspase-independent. The data suggest that Gαi-TNFAIP8-mediated rescue of pre-oncogenic cells enhances progression to oncogenic transformation, providing a selective target to inhibit cellular transformation.

Persistently better treatment planning results of intensity-modulated (IMRT) over conformal radiotherapy (3D-CRT) in prostate cancer patients with significant variation of clinical target volume and/or organs-at-risk.

PURPOSE: To compare the dose coverage of planning and clinical target volume (PTV, CTV), and organs-at-risk (OAR) between intensity-modulated (3D-IMRT) and conventional conformal radiotherapy (3D-CRT) before and after internal organ variation in prostate cancer. METHODS AND MATERIALS: We selected 10 patients with clinically significant interfraction volume changes. Patients were treated with 3D-IMRT to 80 Gy (minimum PTV dose of 76 Gy, excluding rectum). Fictitious, equivalent 3D-CRT plans (80 Gy at isocenter, with 95% isodose (76 Gy) coverage of PTV, with rectal blocking above 76 Gy) were generated using the same planning CT data set ("CT planning"). The plans were then also applied to a verification CT scan ("CT verify") obtained at a different moment. PTV, CTV, and OAR dose coverage were compared using non-parametric tests statistics for V95, V90 (% of the volume receiving 95 or 90% of the dose) and D50 (dose to 50% of the volume). RESULTS: Mean V95 of the PTV for "CT planning" was 94.3% (range, 88-99) vs 89.1% (range, 84-94.5) for 3D-IMRT and 3D-CRT (p=0.005), respectively. Mean V95 of the CTV for "CT verify" was 97% for both 3D-IMRT and 3D-CRT. Mean D50 of the rectum for "CT planning" was 26.8 Gy (range, 22-35) vs 43.5 Gy (range, 33.5-50.5) for 3D-IMRT and 3D-CRT (p=0.0002), respectively. For "CT verify", this D50 was 31.1 Gy (range, 16.5-44) vs 44.2 Gy (range, 34-55) for 3D-IMRT and 3D-CRT (p=0.006), respectively. V95 of the rectum was 0% for both plans for "CT planning", and 2.3% (3D-IMRT) vs 2.1% (3D-CRT) for "CT verify" (p=non-sig.). CONCLUSION: Dose coverage of the PTV and OAR was better with 3D-IMRT for each patient and remained so after internal volume changes.

Control of neuronal firing by dynamic parallel fiber feedback: implications for electrosensory reafference suppression.

The cancellation of self-generated components of sensory inputs is a key function of sensory feedback pathways. In many systems, cerebellar parallel fiber feedback mediates this cancellation through anti-Hebbian plasticity, resulting in the generation of a negative image of the reafferent inputs. Parallel fiber feedback involves direct excitation and disynaptic inhibition as well as synaptic plasticity on multiple time scales. How the dynamics of these processes interact with anti-Hebbian plasticity to shape synaptic inputs and provide a cancellation mechanism remains unclear. In the present study, we investigated the influence of parallel fiber feedback onto pyramidal neurons of the electrosensory lateral line lobe (ELL) in weakly electric fish under open loop conditions. We mimicked naturalistic parallel fiber inputs in an ELL brain slice by implementing an experimentally based model of this synaptic pathway using dynamic clamp. We showed that as parallel fiber activity increases, the effective input to ELL pyramidal neurons changes from net excitation to net inhibition, resulting in a non-monotonic firing response. Using a model neuron, we found that this robust non-monotonic response is due to a shift from balanced excitation and inhibition at low parallel fiber input rates, to dominant inhibition at high input rates. We then showed that this non-monotonic response provides a simple basis for negative image generation. Through changes in the mean activation rate of parallel fibers, the feedback can switch roles between enhancement and suppression of sensory inputs in a manner that is directly determined by the slope of the non-monotonic response curve.

Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans.

BACKGROUND: To compare the dosimetric advantage of three different intensity-modulated radiation therapy (IMRT) plans to a three dimensional (3D) conventional radiation treatment for anal cancer with regards to organs-at-risk (OAR) avoidance, including iliac bone marrow. METHODS: Five patients with T1-3 N0-1 anal cancer and five with T4 and/or N2-3 tumors were selected. Clinical tumor volume (CTV) included tumor, anal canal and inguinal, peri-rectal, and internal/external iliac nodes (plus pre-sacral nodes for T4/N2-3 tumors). Four plans were generated: (A) AP/PA with 3D conformal boost, (B) pelvic IMRT with conformal boost (C) pelvic IMRT with IMRT boost and (D) IMRT with simultaneous integrated boost (SIB). The dose for plans (A) to (C) was 45 Gy/25 followed by a 14.4 Gy/8 boost, and the total dose for plan (D) (SIB) was 59.4 Gy/33. Coverage of both PTV and the volume of OAR (small bowel, genitalia, iliac crest and femoral heads) receiving more than 10, 20, 30, and 40 Gy (V10, V20, V30, V40) were compared using non parametric statistics. RESULTS: Compared to plan (A), IMRT plans (B) to (D) significantly reduced the V30 and V40 of small bowel, bladder and genitalia for all patients. The V10 and V20 of iliac crests were similar for the N0-1 group but were significantly reduced with IMRT for the N2-3/T4 group (V20 for A = 50.2% compared to B = 33%, C = 32.8%, D = 34.3%). There was no statistical difference between 2-phase (arm C) and single-phase (SIB, arm D) IMRT plans. CONCLUSION: IMRT is superior to 3D conformal radiation treatment for anal carcinoma with respect to OAR sparing, including bone marrow sparing.